Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 93
Filtrar
1.
Biomedicines ; 11(11)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-38001981

RESUMO

Salivary pleomorphic adenoma is histopathologically characterized by its colorful stroma with myxoid, chondroid, and hyaline appearances, due to enhanced biosynthesis of extracellular matrix (ECM) molecules and poor vascularity. Thus, pleomorphic adenoma cells embedded in the stroma typically survive under hypoxic conditions. We determined the expression kinetics of ECM molecules, such as perlecan and fibronectin (FN), under hypoxia in SM-AP1 cells which are duct epithelial differentiated cells, and in SM-AP4 cells, which are myoepithelial differentiated cells, cloned from pleomorphic adenoma of the parotid gland. We investigated hypoxia-inducible factor-1α (HIF-1α)-inducing pathways through a variety of ECM molecules in association with their cellular proliferation and migration. We observed that hypoxic conditions with elevated HIF-1α protein levels induced increased expression of perlecan and FN in SM-AP cells than in controls. Moreover, perlecan and FN knockdown reduced the proliferation of SM-AP1 and SM-AP4 cells under hypoxia. Further, SM-AP1 cell migration was enhanced by both perlecan and FN knockdown, whereas SM-AP4 cell migration was increased by perlecan knockdown and inhibited by fibronectin knockdown. The results indicated that pleomorphic adenoma cells can survive under hypoxic conditions by promoting cell proliferation via enhanced synthesis of ECM molecules. Overall, ECM molecules may be a new anti-tumor target under hypoxic conditions.

2.
Acta Cytol ; 66(3): 216-227, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35152223

RESUMO

BACKGROUND: We previously introduced the Five-Parameter System (FPS), which exclusively evaluates keratinized cellular findings, for use in cytology examinations of oral well-differentiated squamous cell carcinoma (SCC) and carcinoma in situ (CIS) specimens, as they occasionally lack nuclear atypia and can be challenging for categorization by The Bethesda System (TBS). This study was conducted to determine whether FPS parameters are detectable even in oral SCC/CIS specimens with apparent nuclear atypia. SUMMARY: Oral cytology specimens were obtained together with biopsy tissue samples. They were obtained from 59 malignant (HSIL and SCC) and 29 not-definitely malignant (NILM to ASC-H) specimens diagnosed using TBS. Following re-confirmation of the original TBS categorization, the specimens were re-evaluated using FPS. One or more of the FPS parameters were noted in 69 of 70 malignant specimens examined, of which 11 had been diagnosed by TBS as not-definitely malignant. The remaining one malignant specimen was diagnosed as SCC with only TBS. FPS parameters #1 (concentric arrangement), #2 (large cell number), #3 (bizarre-shaped cells), #4 (keratoglobules), and #5 (uneven filamentous cytoplasm) were observed only in malignant cases, while none were revealed in not-definitely malignant specimens. Finally, TBS supplemented with FPS achieved sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 100%. KEY MESSAGES: FPS parameters are included in most examinations of oral cytology specimens. Thus, FPS is highly recommended for use in cytology examinations of oral SCC regardless of differentiation degree to confirm judgment based on TBS, a mandatory standard, as well as to cover its limitation of mainly evaluating nuclear atypia. FPS is considered to be an important diagnostic tool for oral cytology, especially in triage cases, which are challenging for TBS. Cytopathology should not be limited to only nuclear findings but be based on whole-cell morphology.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Citodiagnóstico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
3.
Biochem Biophys Res Commun ; 548: 161-166, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33640610

RESUMO

R2TP is a well-conserved molecular chaperone complex, composed of Pontin, Reptin, RPAP3, and PIH1D, in eukaryotes. Recent studies have suggested an involvement of R2TP in cancer development. However, it remains unclear if it is related to the development of oral squamous cell carcinoma (OSCC), which is the most common type of oral cancer. Here, we identify and investigate the function of R2TP in OSCC development. Immunohistochemical analysis reveals that all of the R2TP components are strongly expressed in normal oral epithelia and OSCC tissues, where actively proliferating cells are abundant. Co-immunoprecipitation assay identifies that R2TP components form a protein complex in OSCC-derived HSC4-cells. Knockdown experiments show that all R2TP components, except for RPAP3, are required for the cell proliferation and migration of HSC-4 cells. Furthermore, we reveal that Pontin contributes to a gain-of-function (GOF) activity of mutp53-R248Q in HSC-4 cells by regulating phosphorylation levels of mutp53 at Ser15 and Ser46. To our knowledge, this study is the first to report the functional involvement of R2TP and its components in the malignant characteristics of OSCC cells.


Assuntos
Carcinogênese/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Complexos Multiproteicos/metabolismo , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , DNA Helicases/metabolismo , Humanos , Complexos Multiproteicos/genética , Proteínas Mutantes/metabolismo , Fosforilação , Proteína Supressora de Tumor p53/metabolismo
4.
Sci Rep ; 10(1): 14586, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32884005

RESUMO

Although emergence of keratin 17 (K17) and reciprocal loss of K13 are immunohistochemical hallmarks for oral mucosal malignancy, we report here findings of K17-positive (+) speckles, possibly equivalent to Civatte bodies, in benign oral lichen planus. Sixty-two biopsy samples from oral lichen planus cases were subjected to immunohistochemical examinations to analyze the distribution as well as histopathogenesis of Civatte bodies. K17 was irregularly positive among oral lichen planus-affected epithelial cells, and K17-positive (+) filamentous structures were irregularly distributed within the cytoplasm in confocal images. K17+ speckles were identified as Civatte bodies, and they were mainly distributed in the interface between epithelial cells and lymphocytic infiltrates (type A, 52.8%), followed by distribution within the epithelial layer (type B, 24.7%) or within the lamina propria with lymphocytic infiltration (type C, 22.5%). Apoptotic figures were often engulfed by macrophages and clearly distinguished from Civatte bodies by the presence TUNEL signals. These results indicate that K17 is a sensitive immunohistochemical marker for Civatte bodies and useful for differential diagnosis of oral lichen planus from other oral mucosal lesions. Civatte bodies are generated from denucleation of K17+ epithelial cells during the process of cell death via dyskeratosis, which is possibly related to blood capillary collapse.


Assuntos
Coloides/análise , Queratina-17/metabolismo , Líquen Plano Bucal/patologia , Mucosa Bucal/patologia , Pele/patologia , Estudos de Casos e Controles , Humanos , Líquen Plano Bucal/metabolismo , Mucosa Bucal/metabolismo , Pele/metabolismo
5.
Exp Cell Res ; 392(1): 112013, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32320683

RESUMO

Apoptotic cell death frequently occurs in human cancer tissues including oral squamous cell carcinoma (SCC), wherein apoptotic tumor cells are phagocytosed not only by macrophages but also by neighboring tumor cells. We previously reported that the engulfment of apoptotic SCC cells by neighboring SCC cells frequently occurs at the invading front. Therefore, we hypothesized that the phagocytosis of these apoptotic cells by tumor cells contributes to disease progression. Herein, using cultured oral SCC cells, we aimed to confirm whether tumor cells actually phagocytose apoptotic cells and to examine whether cellular activities are regulated by the phagocytosis of apoptotic cells. Co-culture experiments showed that living cells could ingest apoptotic cells into phagolysosomes. NSC23766, an inhibitor of Rac1, which is a key regulator of phagocytic cup formation in professional phagocytes, dramatically suppressed the phagocytosis of apoptotic cells by living cells. Additionally, cell migration and the secretion of DKK1, a tumor-promoting protein, were enhanced by co-culture with apoptotic cells, whereas NSC23766 inhibited these effects. These results show that tumor cells can actively phagocytose apoptotic neighbors in a Rac1-dependent manner and that such activity increases their migration. The regulation of apoptotic cell phagocytosis thus represents new directions for therapeutic intervention for oral cancer.


Assuntos
Apoptose/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Fagocitose/genética , Proteínas rac1 de Ligação ao GTP/fisiologia , Aminoquinolinas/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/genética , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Células Cultivadas , Progressão da Doença , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Neoplasias Bucais/genética , Fagócitos/efeitos dos fármacos , Fagócitos/fisiologia , Fagocitose/efeitos dos fármacos , Fagossomos/efeitos dos fármacos , Fagossomos/metabolismo , Fagossomos/patologia , Pirimidinas/farmacologia , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidores
6.
Exp Mol Pathol ; 102(2): 327-336, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28242296

RESUMO

Oral squamous cell carcinomas (SCCs) are frequently associated with pre-invasive lesions including carcinoma in-situ (CIS), and CISs further form lateral interfaces against surrounding normal or dysplastic epithelia (ND). At the interface where keratin (K) 17 positive (+) SCC/CIS cells are in contact with K13+ ND cells, "cell competition" must be evoked between two such different cell types. Thus, the aim of this study was to characterize the histopathology of the SCC/CIS-ND interface and to determine protein profiles around the interface by proteomics. A total of 112 lateral interfaces were collected from 55 CIS and 57 SCC foci, and they were investigated by immunohistochemistry and liquid chromatography-tandem mass spectrometry. The interfaces were morphologically classified into three types: vertical, oblique, and convex. There were several cellular changes characteristic to the interface, including apoptosis and hyaline bodies, which were more emphasized in SCC/CIS sides. The results suggested that ND cells were winners of cell competition against SCC/CIS cells. Then, the interfaces were divided into four vertical segments, and each segment was separately laser-microdissected from tissue sections with immunostaining for K13 or K17; the four segments included SCC/CIS away from (#1) or adjacent to (#2) the interface, and ND adjacent to (#3) or away from (#4) the interface. Proteome analyses revealed approximately 4000 proteins from SCC/CIS sides [#1 and #2] and 2800 proteins from ND sides [#3 and #4]. We quantitatively selected the top 25 proteins including ladinin-1 or interleukin-1 receptor antagonist protein, which were most contrastively increased or decreased in SCC/CIS or ND sides, respectively, and their specific immunohistochemical expression modes were confirmed in tissue sections as well as in cultured SCC cells. These molecules should be involved in the cellular crosstalk toward cell competition at the lateral interface of oral SCC/CIS and would be new candidates for histopathological distinction of oral malignancies.


Assuntos
Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Epitélio/metabolismo , Proteômica , Carcinoma in Situ/metabolismo , Carcinoma de Células Escamosas/metabolismo , Morte Celular , Linhagem Celular Tumoral , Cromatografia Líquida , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Mucosa Bucal/patologia , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
7.
Diagn Cytopathol ; 45(5): 406-417, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28205345

RESUMO

BACKGROUND: The cytology of oral squamous cell carcinoma (SCC) is challenging because oral SCC cells tend to be well differentiated and lack nuclear atypia, often resulting in a false negative diagnosis. The purpose of this study was to establish practical cytological parameters specific to oral SCCs. METHODS: We reviewed 123 cases of malignancy and 53 of non-neoplastic lesions of the oral mucosa, which had been diagnosed using both cytology and histopathology specimens. From those, we selected 12 SCC and 4 CIS cases that had initially been categorized as NILM to ASC-H with the Bethesda system, as well as 4 non-neoplastic samples categorized as LSIL or ASC-H as controls, and compared their characteristic findings. After careful examinations, we highlighted five cytological parameters, as described in Results. Those 20 cytology samples were then reevaluated by 4 independent examiners using the Bethesda system as well as the 5 parameters. RESULTS: Five cytological features, (i) concentric arrangement of orangeophilic cells (indicating keratin pearls), (ii) large number of orangeophilic cells, (iii) bizarre-shaped orangeophilic cells without nuclear atypia, (iv) keratoglobules, and (v) uneven filamentous cytoplasm, were found to be significant parameters. All malignant cases contained at least one of those parameters, while none were observed in the four non-neoplastic cases with nuclear atypia. In reevaluations, the Bethesda system did not help the screeners distinguish oral SCCs from non-neoplastic lesions, while use of the five parameters enabled them to make a diagnosis of SCC. CONCLUSION: Recognition of the present five parameters is useful for oral SCC cytology. Diagn. Cytopathol. 2017;45:406-417. © 2017 Wiley Periodicals, Inc.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Histocitoquímica/normas , Queratinas/química , Mucosa Bucal/patologia , Neoplasias Bucais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Núcleo Celular/ultraestrutura , Citoplasma/ultraestrutura , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia
8.
Hum Pathol ; 57: 51-60, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27436828

RESUMO

We reported that altered cell contact mediated by E-cadherin is an initial event in the pathogenesis of oral epithelial malignancies. To assess other effects of cell adhesion, we examined the expression levels of tight junction (TJ) molecules in oral carcinoma in situ (CIS) and squamous cell carcinoma (SCC). To identify changes in the expression of TJ molecules, we conducted an analysis of the immunohistochemical profiles of claudin-1 (CLDN-1) and zonula occludens-1 (ZO-1) in surgical specimens acquired from patients with oral SCC containing foci of epithelial dysplasia or from patients with CIS. We used immunofluorescence, Western blotting, reverse-transcription polymerase chain reaction, and RNA interference to evaluate the functions of CLDN-1 and ZO-1 in cultured oral SCC cells. TJ molecules were not detected in normal oral epithelial tissues but were expressed in SCC/CIS cells. ZO-1 was localized within the nucleus of proliferating cells. When CLDN-1 expression was inhibited by transfecting cells with specific small interference RNAs, SCC cells dissociated, and their ability to proliferate and invade Matrigel was inhibited. In contrast, although RNA interference-mediated inhibition of ZO-1 expression did not affect cell morphology, it inhibited cell proliferation and invasiveness. Our findings indicated that the detection of TJ molecules in the oral epithelia may serve as a marker for the malignant phenotype of cells in which CLDN-1 regulates proliferation and invasion.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Movimento Celular , Proliferação de Células , Claudina-1/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias Bucais/metabolismo , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Claudina-1/genética , Imunofluorescência , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Invasividade Neoplásica , Fenótipo , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Junções Íntimas/patologia , Fatores de Tempo , Transfecção , Proteína da Zônula de Oclusão-1/genética
9.
Pathology ; 48(3): 219-27, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27020496

RESUMO

To confirm our hypothesis that macrophages recruited to fight against oral squamous cell carcinoma (SCC) invasion are functionally differentiated within neoplastic stromata, we analysed arrangements of macrophage subtypes and cancer-associated fibroblasts (CAFs) in their association with blood vasculatures in the neoplastic stroma. Surgical specimens of oral SCC were immunohistochemically examined for macrophage phenotypes (CD68, CD163, and CD204) and stromal environments (perlecan, connexin 43, and CD31). Human monocytes were co-cultured with ZK-1 cells of oral SCC origin in different culture conditions. SCC stromata were divided into two types: fascicular (fibroblast-rich) and reticular (perlecan-rich). Regardless of stromal types, CD68 positive (+)/CD163+/CD204+ macrophages were recruited when blood vessels were abundant. Connexin 43+ fibroblasts were enriched in the fascicular stroma, where blood vessels were depleted. In co-culture experiments, monocytes, in the presence of ZK-1 cells, showed TNF-α(low)/IL-12(low) and IL-10(high)/VEGF(high)/MMP-9(high) with increased expression levels for fibronectin and perlecan. With direct contact with monocytes, SCC cells also expressed CD68 and CD163. SCC stromata were characterised by CD163+/CD204+ tumour-associated macrophages (TAMs) and connexin 43+ CAFs. TAMs are differentiated from monocytes by the physical contact with oral SCC cells in the perlecan-rich neoplastic stroma, which is also induced by the cross-talk between SCC cells and stromal cells including TAMs.


Assuntos
Carcinoma de Células Escamosas/patologia , Macrófagos/patologia , Neoplasias Bucais/patologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirurgia , Diferenciação Celular , Técnicas de Cocultura , Conexina 43/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibronectinas/metabolismo , Proteoglicanas de Heparan Sulfato/metabolismo , Humanos , Imuno-Histoquímica , Macrófagos/metabolismo , Microvasos/patologia , Monócitos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/cirurgia , Fenótipo , Receptores de Superfície Celular/metabolismo , Receptores Depuradores Classe A/metabolismo , Células Estromais/metabolismo , Células Estromais/patologia
10.
Pathol Res Pract ; 212(5): 426-36, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26965914

RESUMO

The intercellular deposit of perlecan, a basement-membrane type heparan sulfate proteoglycan, is considered to function as a growth factor reservoir and is enhanced in oral epithelial dysplasia and carcinoma in situ (CIS). However, it remains unknown which types of growth factors function in these perlecan-enriched epithelial conditions. The aim of this study was to determine immunohistochemically which growth factors were associated with perlecan in normal oral epithelia and in different epithelial lesions from dysplasia and CIS to squamous cell carcinoma (SCC). Eighty-one surgical tissue specimens of oral SCC containing different precancerous stages, along with ten of normal mucosa, were examined by immunohistochemistry for growth factors. In normal epithelia, perlecan and growth factors were not definitely expressed. In epithelial dysplasia, VEGF, SHH, KGF, Flt-1, and Flk-1were localized in the lower half of rete ridges (in concordance with perlecan, 33-100%), in which Ki-67 positive cells were densely packed. In CIS, perlecan and those growth factors/receptors were more strongly expressed in the cell proliferating zone (63-100%). In SCC, perlecan and KGF disappeared from carcinoma cells but emerged in the stromal space (65-100%), while VEGF, SHH, and VEGF receptors remained positive in SCC cells (0%). Immunofluorescence showed that the four growth factors were shown to be produced by three oral SCC cell lines and that their signals were partially overlapped with perlecan signals. The results indicate that perlecan and its binding growth factors are differentially expressed and function in specific manners before (dysplasia/CIS) and after (SCC) invasion of dysplasia/carcinoma cells.


Assuntos
Carcinoma in Situ/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteoglicanas de Heparan Sulfato/metabolismo , Mucosa Bucal/metabolismo , Neoplasias Bucais/metabolismo , Lesões Pré-Cancerosas/metabolismo , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Proliferação de Células/fisiologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Epitélio/metabolismo , Epitélio/patologia , Fator 7 de Crescimento de Fibroblastos/metabolismo , Proteínas Hedgehog/metabolismo , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
11.
Geriatr Gerontol Int ; 16(2): 237-43, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25656946

RESUMO

AIM: To carry out an oral biopsy survey in geriatric patients from the participating institutions. METHODS: The biopsy records of the participating institutions were reviewed for oral lesions from patients aged 65 years and older diagnosed from 2003 to 2012. Demographic data and the site of the lesions were collected. Histopathological diagnoses were categorized into two categories: non-neoplastic lesions (reactive/inflammatory lesion, cyst, allergic/immunologic disorders, potentially malignant disorders, infection and others) and neoplastic lesions (benign and malignant tumors). Data were analyzed by appropriate statistics using stata11. RESULTS: Of the 76,045 accessioned cases, 11,346 cases (14.92%) were in geriatric patients. The mean age of the patients was 72.98 ± 6.25 years. A total of 5010 cases (44.16%) were diagnosed in males, whereas 6336 cases (55.84%) were diagnosed in females. The male-to-female ratio was 0.79:1. Non-neoplastic lesions outnumbered the neoplastic counterpart. The five most prevalent oral lesions in the geriatric population in the present study in descending order of frequency were squamous cell carcinoma, focal fibrous hyperplasia (irritation fibroma), radicular cyst, osteomyelitis and epithelial dysplasia, respectively. The site of predilection was labial/buccal mucosa, followed by gingiva, mandibular bone, tongue and maxillary bone, respectively. CONCLUSIONS: The geriatric oral lesions from the present study showed a similar trend with studies based on histopathological data, but different from the studies based on clinical data. This study also shed more light on potentially malignant disorders, as well as benign and malignant tumors.


Assuntos
Doenças da Boca/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Masculino
12.
Artigo em Inglês | MEDLINE | ID: mdl-26116019

RESUMO

OBJECTIVE: The aim of this study was to characterize the histologic and immunohistochemical profiles of paradental cyst-lining epithelia to clarify its histopathogenesis. STUDY DESIGN: Ten surgical specimens of paradental cysts were examined for clinical profiles and to determine the histopathologic characteristics of the lining epithelia. Immunohistochemical profiles for keratin (K) subtypes, as well as for perlecan, UEA-I lectin binding, and proliferating cell nuclear antigen (PCNA), were determined and compared. RESULTS: The paradental cyst was clinically characterized by its occurrence in young adults (mean age, 36.8 years; male, 42.8, female 27.8). Eight of the 10 cases arose in the retromolar area. The cyst wall was basically granulation tissue that was attached to the periodontal ligament space. Thin irregular anastomosing epithelial cords lined the cyst walls of immature granulation tissue with vascular dilation and hemorrhage. The intercellular space of the lining epithelia was widened with inflammatory cell infiltrates. Immunohistochemically, the lining was positive for K13, K14, K17, K19, UEA-I binding, and perlecan, suggesting its junctional/sulcular epithelial character. CONCLUSION: The results showed that the paradental cyst was lined by epithelial cells with characteristics of the junctional/sulcular epithelium. The cyst can thus be considered as a kind of inclusion cyst arising in the periodontal pocket, most frequently of the mandibular third molars of young adults.


Assuntos
Cisto Periodontal/patologia , Adolescente , Adulto , Idoso , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Cisto Periodontal/cirurgia
13.
Hum Pathol ; 46(7): 991-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25912757

RESUMO

Based on our previous finding that protease-activated receptor 2 (PAR-2) regulates hemophagocytosis of oral squamous cell carcinoma (SCC) cells, which induces their heme oxygenase 1-dependent keratinization, we have formulated a hypothesis that PAR-2 functions in wider activities of SCC cells. To confirm this hypothesis, we investigated immunohistochemical profiles of PAR-2 in oral SCC tissues and its functional roles in cell proliferation and invasion in SCC cells in culture. The PAR-2 expression modes were determined in 48 surgical tissue specimens of oral SCC. Using oral SCC-derived cell systems, we determined both gene and protein expression levels of PAR-2. SCC cell proliferation and invasive properties were also examined in conditions in which PAR-2 was activated by the synthetic peptide SLIGRL. PAR-2 was immunolocalized in oral SCC and carcinoma in situ cells, especially in those on the periphery of carcinoma cell foci (100% of cases), but not in normal oral epithelia. Its expression at both gene and protein levels was confirmed in 3 oral SCC cell lines including ZK-1. Activation of PAR-2 induced ZK-1 cell proliferation in a dose-dependent manner. PAR-2-activated ZK-1 cells invaded faster than nonactivated ones. The expression of PAR-2 is specific to oral malignancies, and PAR-2 regulates the growth and invasion of oral SCC cells.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias Bucais/metabolismo , Receptor PAR-2/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Invasividade Neoplásica , Oligopeptídeos/farmacologia , Receptor PAR-2/agonistas , Receptor PAR-2/genética , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço
14.
Virchows Arch ; 466(5): 559-69, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25736868

RESUMO

Expression of keratin (K) 13 is replaced with that of K17 when squamous cells of the oral mucosa transform from normal and dysplastic epithelia to carcinoma in situ (CIS) and squamous cell carcinoma (SCC). Since 14-3-3 sigma is functionally associated with K17, we examined possible relationships between expression of K17 and 14-3-3 sigma in oral CIS and SCC tissues by immunohistochemistry. We furthermore examined whether or not K17 expression or knockdown by small interfering RNA (siRNA) modulates the behavior of SCC cells in culture in terms of cell proliferation and migration. In tissue specimens of oral SCC and CIS, the pattern of cytoplasmic expression of 14-3-3 sigma and K17 was similar but neither was expressed in normal or dysplastic epithelia. Both proteins were demonstrated in the cytoplasm of control oral SCC ZK-1 cells, but expression of 14-3-3 sigma changed from cytoplasmic to nuclear upon knockdown of K17. In carcinoma cells, therefore, cytoplasmic localization of 14-3-3 sigma seems to accompany expression of K17. In K17-knockdown cells, proliferation was significantly suppressed at 4 days after seeding. In addition, the cell size of K17-knockdown cells was significantly smaller than that of control cells; as a result of which in the migration experiments, we found delayed closure of scratch wounds but migration as such was not affected. We conclude that K17 expression promotes SCC cell growth and cell size but does not affect cell migration. K17 expression is accompanied by cytoplasmic expression of 14-3-3 sigma, indicative of their functional relationship.


Assuntos
Proteínas 14-3-3/biossíntese , Biomarcadores Tumorais/biossíntese , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Exorribonucleases/biossíntese , Queratina-17/biossíntese , Neoplasias Bucais/patologia , Proteínas 14-3-3/análise , Biomarcadores Tumorais/análise , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Exorribonucleases/análise , Imunofluorescência , Humanos , Imuno-Histoquímica , Queratina-17/análise , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
J Oral Pathol Med ; 44(10): 850-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25401705

RESUMO

BACKGROUND: Oral pemphigus vulgaris (PV), an autoimmune blistering disease, is mainly mediated by autoantibodies against desmoglein (Dsg) 3. However, no attention has been paid to IgG subclasses of the autoantibodies against Dsg3 in the diagnostic procedure for PV. Thus, our aim in this study was to investigate whether Dsg3 and any of IgG subclasses are immunohistochemically colocalized in tissue sections of PV oral mucosa. MATERIALS AND METHODS: Serial sections cut from formalin-fixed paraffin blocks of biopsy specimens of 9 PV cases and those of normal buccal mucosa surgically removed for fibro-epithelial polyps were comparatively examined for immunohistochemical localizations for Dsg3, IgG4, and IgG. RESULTS: Dsg3 was demonstrated in a dot-like pattern on the cell border and in the cytoplasm of the whole epithelial layer in both normal and PV specimens, while its staining was irregular among floating epithelial sheets of PV. IgG4 was also demonstrated in a punctuated fashion on the cell border among floating epithelial sheets, which was nearly identical to the immunohistochemical profile of Dsg3. In addition to being detected in the epithelial part, IgG4 signals were prominently localized in plasma cells scattered in the granulation tissue, where ratios of IgG4-positive (+) plasma cells to IgG+ cells were extraordinarily higher (mean 28%) than those in normal mucosa. DISCUSSION: These findings confirmed for the first time that autoantibodies against Dsg3 are mainly composed of IgG4 in oral PV and that the combined immunohistochemistry for Dsg3 and IgG4 can be a valuable aid in confirming a histopathological diagnosis of PV.


Assuntos
Autoanticorpos/imunologia , Desmogleína 3/imunologia , Imunoglobulina G/imunologia , Pênfigo/imunologia , Adulto , Idoso , Biópsia , Desmogleína 3/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Pênfigo/diagnóstico , Pênfigo/patologia
16.
Lab Invest ; 94(11): 1260-72, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25264705

RESUMO

Milk fat globule--epidermal growth factor (EGF)--factor VIII (MFG-E8) is a secreted glycoprotein that promotes clearance of apoptotic cells by bridging phosphatidylserine on apoptotic cells and integrin αvß3/5 on phagocytes. High expression of MFG-E8 has been reported in various types of cancer in humans. Apoptotic figures are frequently found in the surgical samples of oral squamous cell carcinoma (SCC) and carcinoma in situ, and we have often observed apoptotic carcinoma cells engulfed by macrophages or even by neighboring carcinoma cells. Thus we hypothesized that MFG-E8 might promote engulfment of apoptotic carcinoma cells by living carcinoma cells and that MFG-E8 expressed by carcinoma cells could contribute to tumor progression. The aim of this study was to elucidate the biological role of MFG-E8 in oral SCC. Fifty-three surgical specimens of oral SCC were used for immunohistochemistry for MFG-E8, and the expression profiles were correlated with clinicopathological properties. Also, we examined the MFG-E8 expression patterns and functions using three human oral SCC cell lines. Most of the cases had MFG-E8-positive SCC cells, and the expression of MFG-E8 was correlated with such clinicopathological features as tumor size, pathological stage, locoregional recurrence, scattering invasion pattern, and SCC cell figures engulfing apoptotic SCC cells. The MFG-E8 staining was enhanced in apoptotic SCC cells, some of which were apparently engulfed by the neighboring SCC cells. ZK-1 cells showed high MFG-E8 expression, and its localization was found in the cytoplasm and the cell surface. Transient MFG-E8 knockdown by siRNA in ZK-1 decreased cell proliferation and invasiveness and increased cell death. Thus we have demonstrated that MFG-E8 promotes tumor progression in oral SCC and that it might be involved in the clearance of apoptotic SCC cells by living SCC cells.


Assuntos
Antígenos de Superfície/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas do Leite/metabolismo , Neoplasias Bucais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Adulto Jovem
17.
Pathol Res Pract ; 210(12): 1123-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25086676

RESUMO

We report a rare case of radiation-induced undifferentiated high-grade pleomorphic sarcoma (UPS) (malignant fibrous histiocytoma, MFH) in the right mandible of a 44-year-old woman. The patient had suffered from osteomyelitis of the same region of the mandible for several years, which was considered to be due to radiotherapy for a malignant lymphoma in her right neck 19 years before. The tumor appeared as an exophytic and invasive growth in the molar region of the mandible. Histopathologically, the tumor consisted of an interlacing proliferation of vimentin-immunopositive spindle-shaped fibroblastic cells with bizarre nuclei with high Ki-67 labeling scores, and tumor cells showed storiform patterns mixed with pleomorphic cells. Taking the history of radiation into consideration, we diagnosed the lesion as radiation-induced MFH/UPS. Including the present case, there have been only 14 documented cases of radiation-induced UPS in the jawbone, and this is the first UPS case arising in the follow-up period of long-standing osteomyelitis.


Assuntos
Histiocitoma Fibroso Maligno/etiologia , Histiocitoma Fibroso Maligno/patologia , Mandíbula/patologia , Neoplasias Induzidas por Radiação/patologia , Osteomielite/patologia , Adulto , Feminino , Humanos , Gradação de Tumores , Osteomielite/complicações , Osteomielite/diagnóstico , Radioterapia/efeitos adversos
18.
Biomed Res Int ; 2014: 823968, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25050372

RESUMO

BACKGROUND: Local recurrence remains a challenging clinical issue for the treatment of oral squamous cell carcinoma (SCC). We analyzed retrospectively how effective the frozen section technique (FS) was against recurrences of oral SCC. METHODS: We screened 343 surgical samples from 236 patients who had oral SCC, carcinoma in situ (CIS), or epithelial dysplasia, and we followed up their clinical outcomes for at least 5 years. Histopathological states of surgical margins were compared between FS and surgical materials in relapse and relapse-free groups, respectively. RESULTS: Among the 236 patients, 191 were classified into the relapse-free group, and 45 into the relapse group. FS was more frequently performed in the relapse-free group (128/191) than in the relapse group (83/152). Histopathologically, moderate dysplasia or CIS (borderline malignancies) and SCC were recognized in 55 samples of the relapse-free group and in 57 of the relapse group. For those surgical margins with borderline malignancies, additional incisions were performed in 38 of the 55 relapse-free cases, which reduced to 20 from the 38 margins with borderline malignancies (47.4% reduction), and in 39 of the 57 relapse cases, which reduced to only 3 of 39 (7.7% reduction). CONCLUSIONS: The intraoperative assessment of surgical margins by FS is essential in preventing recurrences of oral mucosal malignancies.


Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Secções Congeladas , Cuidados Intraoperatórios , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Prognóstico , Resultado do Tratamento , Adulto Jovem
19.
J Oral Pathol Med ; 43(10): 778-84, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24931829

RESUMO

BACKGROUND: We have reported that neutrophilic infiltration was associated with round-shaped dyskeratosis foci, a kind of keratin pearl, of oral carcinoma in situ and that those inflammatory cells are recruited from intra-epithelially entrapped blood vessels. Based on these lines of evidence, we have formulated a hypothesis that keratin pearls are terminally degraded by neutrophils. To confirm this hypothesis, we investigated immunohistochemically stepwise degradation of keratin pearls in oral squamous cell carcinoma (SCC) to clarify any other type scavenger cells in addition to neutrophils are involved in this particular degradation process. METHODS: Neutrophils (neutrophil elastase) and macrophage subpopulations (CD68, CD163 and CD204) were immunohistochemically localized in 30 cases of oral SCC with typical round-shaped keratin pearls. SCC cells were revealed by immunohistochemistry for keratin (K) 17, and blood vessels were demonstrated by CD31. RESULTS: Keratin pearl degradation process was divided into four steps: (i) intact stage: no macrophage infiltration but minimal neutrophils were found in keratin pearls; (ii) neutrophil recruit stage: no macrophage infiltration but focal neutrophilic infiltration within the pearls; (iii) neutrophil predominant stage: dense neutrophil infiltration with minimal macrophages and segregated keratinized cancer cells strongly positive for K17; and (iv) macrophage predominant stage: dense infiltration of CD68-, CD163 (mononuclear)- and CD204 (multinucleated)-positive macrophages engulfing detached keratinized SCC cells. CONCLUSION: Keratin pearl degradation in oral SCC is strictly regulated by two types of scavenger cells: neutrophils, which perform initial tasks, and macrophages, which reciprocally take over from neutrophils the role to finalize the degradation processes.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Queratinas/metabolismo , Macrófagos/metabolismo , Neoplasias Bucais/metabolismo , Neutrófilos/metabolismo , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Carcinoma de Células Escamosas/patologia , Humanos , Queratina-17/análise , Elastase de Leucócito/análise , Ativação de Macrófagos/fisiologia , Macrófagos/classificação , Neoplasias Bucais/patologia , Infiltração de Neutrófilos/fisiologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Proteólise , Receptores de Superfície Celular/análise , Receptores Depuradores/análise , Receptores Depuradores Classe A/análise
20.
J Oral Pathol Med ; 43(8): 627-36, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24697873

RESUMO

BACKGROUND: We have demonstrated the induction of perlecan-rich stroma of oral squamous cell carcinoma (SCC) on and after its start of invasion. However, it remains unknown how such a neoplastic stroma is actually arranged in tumor tissues. METHODS: To this end, tissue microarray samples, in which keratin and perlecan were contrastively labeled by immunohistochemistry, were three-dimensionally analyzed using digital images and image analysis software to demonstrate the relationship between SCC foci and the perlecan-positive stromal space or that between carcinoma in situ (CIS) and invasive SCC foci. RESULTS: The three-dimensional (3D) reconstruction demonstrated three kinds of perlecan profiles for inside (I) and outside (O) areas of the carcinoma cell focus: mode 1, I(+)/O(-) ; mode 2, I(+)/O(+) ; and mode 3, I(-)/O(+). Mode 1 was seen in CIS as well as SCC tumor massifs in the surface part. Mode 2 was seen in small SCC foci, which seemed isolated in 2D sections but were mostly continuous with the tumor massif in 3D reconstructions. Mode 3 was limited to small SCC foci, which were truly segregated from the tumor massif. CONCLUSIONS: The results indicated that the 2D SCC focus isolation could not be regarded as invasion but that the SCC foci surrounded by perlecan-positive stroma (modes 2 and 3) could be regarded as a more objective measure for invasion of SCC. This is the first 3D tissue-level demonstration of the neoplastic stroma space induced with oral SCC invasion, the presence of which we have predicted based on our previous 2D and tissue culture evidence.


Assuntos
Carcinoma de Células Escamosas/química , Proteoglicanas de Heparan Sulfato/química , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Neoplasias da Língua/química , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/química , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Tecido Conjuntivo/química , Tecido Conjuntivo/patologia , Epitélio/química , Epitélio/patologia , Feminino , Humanos , Imuno-Histoquímica , Queratina-13/análise , Queratina-17/análise , Queratina-19/análise , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Lesões Pré-Cancerosas/química , Lesões Pré-Cancerosas/patologia , Análise Serial de Tecidos , Neoplasias da Língua/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...