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1.
J Infect Chemother ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936771

RESUMO

This severe monkeypox case described a 23-year-old male with advanced HIV-1 disease presenting perirectal abscess, extensive anal ulcerative lesions requiring colostomy, and tecovirimat resistance. Radiologically non-liquefied perirectal abscess presented diagnostic challenges highlighting the complexity of aggressive monkeypox manifestations in immunocompromised individuals.

2.
Aesthet Surg J ; 42(7): NP489-NP500, 2022 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-35148368

RESUMO

BACKGROUND: Costal cartilage is commonly employed as a dorsal implant in Asian rhinoplasty. To achieve better outcomes, it is important to know which types of costal cartilage are most appropriate for dorsal augmentation. OBJECTIVES: The authors investigated how various forms of costal cartilage affect the surrounding tissues and their resorption over time, as well as their clinical appearance, using histomorphological analysis. METHODS: Cartilage samples were collected from the anterior chest wall of 10 rabbits. Four forms of cartilage-2-mm solid block, 1-mm solid block, diced, and crushed-were prepared and inserted into the subcutaneous tissue pockets of the nasal dorsum of each rabbit. The animals were killed 3 and 6 months later, and graft specimens were examined. RESULTS: Histomorphological analysis revealed important findings of the cartilage and surrounding tissues. The thickness of thick cartilage significantly decreased over time, but the thickness of thin cartilage did not significantly change (P = 0.038). Additionally, the thick cartilages showed a lower degree of vascularization than the thin cartilages (P < 0.001). A comparison of the cartilage forms revealed that the diced cartilages had better chondrocyte survival than the solid block cartilages (P < 0.001). Fat tissues were prominently observed surrounding the diced cartilages at 3 months (P = 0.01), and fibrosis was more prominently observed in the crushed cartilage than in the other types of cartilages (P = 0.04 and P = 0.005 at 3 and 6 months, respectively). CONCLUSIONS: This study revealed differences in resorption depending on the thickness of the costal cartilage in rabbits. Among the various forms of costal cartilages, diced and thin solid-block cartilage were the best option for dorsal augmentation when considering long-term graft survival.


Assuntos
Cartilagem Costal , Rinoplastia , Tecido Adiposo/transplante , Animais , Povo Asiático , Cartilagem/transplante , Humanos , Nariz , Coelhos
3.
J Cancer ; 13(3): 869-876, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154455

RESUMO

Purpose: This study aimed to investigate the relationship between DNA damage response (DDR) related protein expression and clinical outcomes of patients with stage II and III gastric cancer undergoing gastrectomy. Materials and Methods: From January 2005 to December 2017, 217 gastrectomized patients with stage II and III gastric cancer were analyzed for disease-free and overall survival (DFS and OS, respectively) based on their DDR expression status. We performed the immunohistochemical assessment of MLH1, MSH2, at-rich interaction domain 1 (ARID1A), poly adenosine diphosphate-ribose polymerase 1 (PARP-1), breast cancer susceptibility gene 1 (BRCA1), and ataxia-telangiectasia mutated (ATM) using formalin-fixed paraffin-embedded (FFPE) samples. Results: Among the 217 patients studied, the most common DDR gene whose expression was suppressed was high PARP-1 (n = 120, 55.3%), followed by ATM (n = 62, 28.6%), ARID1A (n = 45, 20.7%), MLH1 (n = 33, 15.2%), BRCA1 (n = 25, 11.5%), and MSH2 (n = 9, 4.1%). The low-expression PARP-1 group exhibited a significantly shorter 5-year OS rate than the high-expression PARP-1 group (48.1% vs. 62.7%; HR 1.519, 95% CI = 1.011-2.283, P = 0.044). In the multivariate OS analysis, TNM stage (II vs. III) (HR = 5.172, P < 0.001), low PARP-1 expression (HR = 1.697, P = 0.013) and adjuvant chemotherapy (HR = 0.382, P < 0.001) were the only significant prognostic factors. Conclusions: Low PARP-1 expression level could be an indicator of poor prognosis in gastrectomized patients with stage II and III gastric cancer.

4.
BMC Cancer ; 21(1): 1176, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732161

RESUMO

BACKGROUND: According to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who were previously treated with gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to haematological toxicity. There has been limited information on the clinical benefits and toxicity of this regimen in real-world settings. In this study, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure. METHODS: We conducted a single institution, retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80 mg/m2) with 5-FU/LV every 2 weeks. Kaplan-Meier analysis was performed to obtain median progression free survival and median overall survival. The hazard ratio and 95% confidence interval (CI) were estimated using a stratified Cox regression model. A multivariate Cox proportional hazards regression model was used to identify the effects of clinical factors. RESULTS: Fifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% CI 1.8-3.7) and median overall survival was 7.0 months (95% CI 6.0-7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced grade 3 or 4 adverse events, most commonly neutropenia (58.8%). Most non-haematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1-18.4). CONCLUSIONS: Nal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, following gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Nal-IRI plus 5-FU/LV following gemcitabine with nab-paclitaxel is a feasible sequential treatment option in patients with metastatic pancreatic cancer. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Fluoruracila/administração & dosagem , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Albuminas/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/secundário , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Esquema de Medicação , Feminino , Fluoruracila/efeitos adversos , Humanos , Irinotecano/efeitos adversos , Irinotecano/análogos & derivados , Estimativa de Kaplan-Meier , Leucovorina/efeitos adversos , Lipossomos , Masculino , Pessoa de Meia-Idade , Nanoconjugados/administração & dosagem , Nanoconjugados/efeitos adversos , Neutropenia/induzido quimicamente , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Gencitabina
5.
Int J Clin Exp Pathol ; 13(5): 995-1007, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509071

RESUMO

The mTOR signaling pathway has been linked to various cancers, but the contribution of alterations in this pathway to clinicopathological characteristics have not been established in gastric cancer. To investigate PIK3CA mutations and the expression of proteins in the PI3K/Akt/mTOR signaling pathway in sporadic gastric cancer. We analyzed PIK3CA mutation and microsatellite instability as well as immunohistochemical expressions of p-Akt, PTEN, p-mTOR, p-4EBP1, p-S6, p-p70S6, and eIF4E in 368 FFPE (formalin-fixed paraffin embedded) tissue from patients with sporadic gastric cancer. Associations between expression and clinicopathologic parameters and patient survival were evaluated. We found PIK3CA mutations in 4 of 173 cases (2.3%). In immunohistochemical analyses, we detected positive p-Akt expression in 22.0% of cases (81/368), negative PTEN expression in 21.5% of cases (79/368), positive p-mTOR expression in 68.6% of cases (243/354), positive p-4EBP1 expression in 58.2% of cases (202/347), positive p-S6 expression in 42.7% of cases (148/347), positive p-p70S6 expression in 51.1% of cases (179/350), and positive eIF4E expression in 78.3% of cases (275/351). In a clinicopathologic analysis, intestinal type was significantly associated with positive p-4EBP1 expression (P < 0.001). In a Kaplan-Meier survival analysis, PTEN loss (P = 0.002) and pS6 positivity (P = 0.043) are significantly associated with reduced overall survival (OS). PTEN loss (P = 0.001), pS6 positivity (P = 0.009), and eIF4E positivity (P = 0.003) are significantly associated with reduced disease free survival (DFS) (disease free survival). In Cox regression multivariate analysis, PTEN loss was an independent factor of reduced time. Alterations of mTOR pathway protein expression are associated with reduced survival in gastric cancer. Significance was noted in the association of pS6 positivity and eIF4E positivity e with reduced survival in univariate analysis and the association of PTEN loss and reduced DFS in univariate analysis as well as multivariate analysis for DFS.

6.
Prostate ; 77(14): 1438-1445, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28845585

RESUMO

BACKGROUND: Prostate cancer is considered to be highly heterogeneous, with various morphologic features and biologic behaviors. The TMPRSS2-ERG gene fusion is the most frequently observed genetic aberration in prostate cancer. The aim of this study was to elucidate the intrafocal heterogeneity of ERG gene fusion status. METHODS: ERG immunohistochemistry (IHC) was performed in samples from 168 prostate cancer patients who had undergone radical prostatectomy, and 40 cases showing ERG-positive IHC staining were selected for tissue microarray (TMA) construction. Two to six representative cores were selected from each tumor focus. In the cases with heterogeneous ERG IHC staining intensity, the areas showing different intensities were separately selected. Using the TMA blocks, IHC and fluorescence in situ hybridization (FISH) were conducted to evaluate the heterogeneity of ERG protein expression and ERG fusion gene patterns, respectively, in a single tumor focus. Heterogeneity of ERG IHC staining was defined as the simultaneous presence of negative and positive cores in the same tumor focus. Heterogeneity of ERG FISH was defined by the presence of cores with positive and negative FISH signals or cores with break-apart and interstitial deletion FISH signals in the same tumor focus. RESULTS: A total of 202 TMA cores were isolated from 40 ERG-positive cases. Of the 202 total cores, 19 were negative for ERG IHC staining, and 46 showed 1+, 52 showed 2+, and 85 showed 3+ ERG staining intensity. Eleven cores were negative for ERG FISH signal, 119 cores showed ERG break-apart FISH signals, and the remaining 72 cores revealed interstitial deletion. Intrafocal heterogeneity of ERG IHC staining was found in 20% (8/40) of cases, and intrafocal heterogeneity of ERG gene fusion pattern was found in 32.5% (13/40) of cases. CONCLUSIONS: In summary, this study showed significantly frequent intrafocal heterogeneity of ERG protein expression, gene fusion status and fusion pattern. This heterogeneity can be caused by the development of subclones during cancer progression or the intermingling of different tumors.


Assuntos
Proteínas de Fusão Oncogênica/genética , Próstata/patologia , Neoplasias da Próstata , Biomarcadores Tumorais/genética , Progressão da Doença , Heterogeneidade Genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
7.
Pathol Int ; 66(10): 571-577, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27595761

RESUMO

Epithelioid angiomyolipoma (EAML) is considered to be a potentially malignant tumor and requires a differential diagnosis from renal cell carcinoma. In this study, we assessed the clinicopathologic features of renal EAML and evaluated the prognostic significance. Among 78 angiomyolipoma (AML) patients, a total of 5 EAMLs were identified, accounting for 6.4% of the total AML cases. The mean age was 41.4 years, and the average tumor size was 12.7 cm in diameter. Association of tuberous sclerosis complex was identified in two cases. One EAML case showed malignant behavior with local recurrence and distant metastasis. The malignant EAML had a larger tumor size, a higher percentage of epithelioid component and atypical epithelioid cells, ≥2 mitoses per 10 high power fields with atypical mitosis, necrosis, extrarenal extension, and carcinoma-like growth pattern. Furthermore, the malignant case revealed p53 immunoreactivity and decreased membranous E-cadherin expression. Pathologic evaluation of adverse prognostic factors will be helpful for risk stratification and prognosis estimation of EAML patients.


Assuntos
Angiomiolipoma/patologia , Células Epitelioides/patologia , Neoplasias Renais/patologia , Adulto , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
8.
Pathol Res Pract ; 211(11): 824-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26296917

RESUMO

INTRODUCTION: The members of the Tumor Necrosis Factor Superfamily (TNFSF), including A PRoliferation Inducing Ligand (APRIL), have been studied in RCC and other tumors. In this study, we investigated the expression of APRIL in resected clear cell renal cell carcinoma (CCRCC) samples by immunohistochemistry (IHC) and analyzed its association with the clinicopathologic characteristics and prognosis of the patients. METHODS: We examined 206 CCRCC samples from patients who underwent radical or partial nephrectomy at Seoul National University Hospital between 1999 and 2002. Tissue microarray (TMA) blocks were made, and immunohistochemical staining for APRIL expression was performed. RESULTS: We classified the IHC results as high expression or low expression. Of the 206 cases, 89 cases (43.2%) were classified as showing high expression, and 117 cases (56.8%) showed low expression. The high expression of APRIL was significantly correlated with higher Fuhrman nuclear grade and higher pathologic stage (p=0.000 and 0.004), and we observed that the high expression of APRIL was significantly correlated with the overall survival of the patients (p=0.045) and cancer-specific survival (p=0.020), but was not correlated with disease-free survival (p=0.106). In multivariate analysis adjusted for Fuhrman nuclear grade and pathologic stage, the high expression of APRIL was not an independent prognostic factor for CCRCC, as determined by overall survival (p=0.830) and cancer-specific survival (p=0.792). CONCLUSIONS: We found that the high expression of APRIL in CCRCCs was correlated with high Fuhrman nuclear grade, high pathologic stage, and poor overall and cancer-specific survival of the patients. However, it did not correlate with disease-free survival and was not an independent prognostic factor.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/biossíntese , Adulto , Idoso , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise Serial de Tecidos , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/análise , Regulação para Cima
9.
Hum Pathol ; 46(3): 454-60, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25628030

RESUMO

Clear cell renal cell carcinoma (CCRCC) is the most common renal cell carcinoma. It has a relatively unfavorable prognosis compared to other common renal cell carcinomas. Recently, comprehensive molecular studies in CCRCC revealed important genetic alterations, including changes in the VHL, PBRM1, and ARID1A genes. The expression of ARID1A protein is associated with tumor progression and prognosis in many cancers. This study aimed to evaluate the nuclear expression of ARID1A in CCRCC and to assess its expression with the clinical prognosis. The nuclear expression of ARID1A was evaluated in 290 cases of CCRCC by immunohistochemistry. To determine the clinicopathological association with ARID1A, each of the cases was divided into 2 groups, low- and high-expression groups, according to the average proportion of nuclear staining. Decreased ARID1A expression was associated with the higher nuclear grade and higher pTNM stage (P < .001 and P = .013, respectively). The ARID1A low-expression group revealed significantly shorter cancer-specific and progression-free survival times (P = .001 and P < .001, respectively). Furthermore, Cox regression analysis showed that ARID1A expression was an independent prognostic factor for progression-free survival (P = .009). These results suggest that nuclear expression of ARID1A may serve as a new prognostic marker in CCRCC patients.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Renais/química , Neoplasias Renais/química , Proteínas Nucleares/análise , Fatores de Transcrição/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Núcleo Celular/química , Criança , Proteínas de Ligação a DNA , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Sobrevida , Adulto Jovem
10.
Int J Clin Exp Pathol ; 7(9): 6141-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25337262

RESUMO

The long-term mortality risk from prostate cancer increases in lymph node (LN) positive patients. This study was done to assess the effect of lymph node Gleason score (LNGS) on prognosis in patients with LN-positive prostate cancer. Among the 1,415 patients who received pelvic lymph node dissection (PLND), 117 (8.4%) patients had a positive LN. The PGS of the prostate specimens and the LNGS of the positive LNs were assessed by uropathologists. The median age of patients at surgery was 67 years (interquartile range [IQR], 62-71 years) and the median follow-up duration was 44.3 months (IQR, 27.0-78.5 months). Pathologic Gleason scores (PGS) of 6-9 included one (0.9%), 53 (49.5%), 22 (20.6%), and 31 (29.0%) patients. The median total number of retrieved LNs was 9.0 (IQR, 5.3-12.8). The median number of positive LNs was one (IQR, 1-2). Cancer architecture with a Gleason pattern and score were observed in LNs as in ordinary prostate specimens. LNGS 6-9 included nine (8.1%), 57 (51.4%), 31 (27.9%), and 14 (12.6%) patients. The speaman's analysis showed the meaningful correlation between PGS and LNGS (P = 0.249, P = 0.011). The univariate analysis showed that the number of positive LNs and LNGS were significantly associated with prostate cancer-specific survival (P = 0.028; P = 0.005). The same architecture that is seen in the prostate was seen in positive LNs, and LNGS may be a significant prognostic factor in patients with LN-positive prostate cancer.


Assuntos
Adenocarcinoma/secundário , Linfonodos/patologia , Neoplasias da Próstata/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Idoso , Biópsia , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Prostatectomia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
11.
Korean J Pathol ; 47(5): 426-32, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24255630

RESUMO

BACKGROUND: Due to advancements in treatment of metastatic and advanced renal cell carcinoma (RCC), it has become increasingly important to diagnose metastatic RCC and the specific subtype. In this study, we investigated the diverse histologic features of metastatic clear cell renal cell carcinoma (CCRCC) cases in comparison with corresponding primary lesions. METHODS: We identified 119 metastatic CCRCC cases from 81 corresponding primary lesions diagnosed between 1995 and 2010 and evaluated the diverse histologic and immunohistochemical features of these lesions. RESULTS: A total of 44 primary lesions (54.3%) had a non-clear cell component in addition to a typical clear cell component. Of the 119 metastatic lesions, 63 lesions (52.9%) contained a non-clear cell component, and 29 metastatic lesions were composed of a non-clear cell component only. Rhabdoid features were the most frequent non-clear cell histology among the metastatic lesions. Metastatic CCRCCs mainly showed positive CD10 and epithelial membrane antigen staining and negative cytokeratin 7 staining. CONCLUSIONS: Metastatic CCRCC commonly showed a variety of histologic features. If there is a difficulty to diagnose metastatic CCRCC due to a variety of histologic features or small biopsy specimen, histologic review of the primary lesion and immunohistochemical analysis can help determine the correct diagnosis.

12.
Korean J Pathol ; 47(5): 452-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24255633

RESUMO

BACKGROUND: Recently, there have been a few reports of renal cell carcinoma (RCC) cases with anaplastic lymphoma kinase (ALK) gene fusion. In this study, we screened consecutively resected RCCs from a single institution for ALK protein expression by immunohistochemistry, and then we performed fluorescence in situ hybridization to confirm the ALK gene alteration in ALK immunohistochemistry-positive cases. METHODS: We screened 829 RCCs by ALK immunohistochemistry, and performed fluorescence in situ hybridization analysis using ALK dual-color break-apart rearrangement probe. Histological review and additional immunohistochemistry analyses were done in positive cases. RESULTS: One ALK-positive case was found. Initial diagnosis of this case was papillary RCC type 2. This comprises 0.12% of all RCCs (1/829) and 1.9% of papillary RCCs (1/53). This patient was a 44-year-old male with RCC found during routine health check-up. He was alive without evidence of disease 12 years after surgery. The tumor showed a papillary and tubular pattern, and showed positivity for CD10 (focal), epithelial membrane antigen, cytokeratin 7, pan-cytokeratin, PAX-2, and vimentin. CONCLUSIONS: We found the first RCC case with ALK gene rearrangement in Korean patients by ALK immunohistochemistry among 829 RCCs. This case showed similar histological and immunohistochemical features to those of previous adult cases with ALK rearrangement, and showed relatively good prognosis.

13.
Hum Pathol ; 44(10): 2047-54, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23668999

RESUMO

Smad2, Smad3, and Smad4 are components of the transforming growth factor ß signaling pathway associated with tumorigenesis. The expression of these proteins is associated with tumor progression and prognosis of many cancers. This study aimed to evaluate the nuclear expression of Smad2, Smad3, and Smad4 in clear cell renal cell carcinoma and to assess the clinical significance and prognostic value of their expression patterns. The nuclear expression levels of Smads were evaluated in 637 cases of clear cell renal cell carcinomas using immunohistochemistry. To determine the statistical significance of Smad expression in clear cell renal cell carcinoma, each of the cases were divided into 2 groups (low and high expression groups) according to the extent of nuclear staining. Nuclear expressions of Smad3 and Smad4 were inversely correlated with the patient's age, the nuclear grade, the tumor size, and the pTNM stage. The Smad3-low and Smad4-low groups showed significantly shorter cancer-specific and progression-free survival times. Furthermore, multivariate analysis showed that both Smad3 and Smad4 were independent predictors for progression-free survival (P = .008 and P = .022, respectively). However, Smad2 expression was not related to clinicopathologic parameters and patients' survival. These results suggest that nuclear expressions of Smad3 and Smad4 were related to prognosis of clear cell renal cell carcinoma patients and may serve as novel prognostic markers in clear cell renal cell carcinoma patients.


Assuntos
Carcinoma de Células Renais/metabolismo , Núcleo Celular/metabolismo , Neoplasias Renais/metabolismo , Proteínas Smad/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Núcleo Celular/patologia , Feminino , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , República da Coreia/epidemiologia , Taxa de Sobrevida , Adulto Jovem
14.
J Korean Med Sci ; 28(4): 593-601, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23579442

RESUMO

Alpha-internexin (INA) is a proneuronal gene-encoding neurofilament interacting protein. INA is overexpressed mostly in oligodendroglial phenotype gliomas, is related to 1p/19q codeletion, and is a favorable prognostic marker. We studied INA expression in oligodendrogliomas (ODGs) and glioblastomas (GBMs) to verify its association with several molecular phenotypes, 1p/19q codeletion, and epidermal growth-factor-receptor (EGFR) amplification. A total of 230 low- and high-grade ODG and GBM cases was analyzed for INA expression by immunohistochemical staining; and 1p/19q and EGFR gene status was examined by fluorescence in-situ hybridization. INA was positive in 80.3% of ODGs and in 34.3% of GBMs. 1p/19q codeletion was detected in 77.0% of ODGs and 5.5% of GBMs. INA and 1p/19q codeletion were strongly correlated (P < 0.001). The specificity of INA expression for 1p/19q codeletion was 70.8%, while sensitivity was 100%; positive predictive value was 72.5%, and negative predictive value was 29.2% in all 228 tumors. INA expression was correlated with better progression-free survival (PFS) and overall survival (OS) (P = 0.001). In conclusion, INA expression has high specificity and sensitivity to predict 1p/19q codeletion, and it is well correlated with PFS of both ODGs and GBMs. Therefore, INA expression could be a simple, reliable, and favorable prognostic and surrogate marker for 1p/19q codeletion and long term survival.


Assuntos
Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Proteínas de Filamentos Intermediários/metabolismo , Oligodendroglioma/metabolismo , Adulto , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 19 , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Deleção de Genes , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Proteínas de Filamentos Intermediários/genética , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/mortalidade , Oligodendroglioma/patologia , Fenótipo , Valor Preditivo dos Testes , Prognóstico
15.
Korean J Pathol ; 46(5): 423-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23136568

RESUMO

BACKGROUND: Transmembrane protease serine 2-ETS related gene (TMPRSS2-ERG) gene fusion, the most common genetic alternation in prostate cancer, is associated with protein expression of the oncogene ERG. Recently, an immunohistochemical staining method using an anti-ERG antibody was shown to have a strong correlation with altered ERG protein expression. METHODS: We analyzed a total of 303 radical prostatectomy specimens (obtained from Korean prostate cancer cases) using a constructed tissue microarray and ERG immunohistochemical staining. Thereafter, we evaluated the association between ERG expression and clinicopathological factors. RESULTS: The ERG-positive rate was 24.4% (74/303) and significantly higher ERG expression was observed in the subgroup with a lower Gleason score (p=0.004). Analysis of the histologic pattern of prostate adenocarcinomas revealed that tumors with discrete glandular units (Gleason pattern 3) displayed higher frequency of ERG expression (p=0.016). The ERG-positive rate was lower than that found (approximately 50%) in studies involving western populations. Other factors including age, tumor volume, initial protein-specific antigen level, a pathological stage and margin status were not significantly related with the ERG expression. CONCLUSIONS: ERG immunohistochemical staining is significantly higher in tumors with well-formed glands and is associated with a lower Gleason score.

16.
Korean J Pathol ; 46(3): 237-45, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23110009

RESUMO

BACKGROUND: The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines. METHODS: Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines. RESULTS: Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity. CONCLUSIONS: This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.

17.
J Korean Med Sci ; 27(9): 1073-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22969255

RESUMO

This study was conducted to investigate the effects of erythropoietin (Epo) on both acute and chronic limb ischemia (ALI and CLI) and to evaluate the differences in mechanisms according to the method of Epo administration. Hindlimb ischemia was made in BALB/c mice with femoral artery ligation. The mice were divided into four groups: Group 1 (control, no treatment), Group 2 (ALI, early multiple doses), Group 3 (ALI, early single high dose), Group 4 (CLI, late multiple doses). Blood flow ratio significantly increased in Group 2 in 4 weeks. Expression of pAkt and Erythropoietin receptor were significantly higher in Group 2 on postoperative day (POD) 7. The number of CD31- and vascular endothelial growth factor-positive cells were significantly higher in Group 2 on POD 7 and 56. Group 3 and 4 showed a tendency of higher cell counts than the control. The early sustained Epo was effective in improving blood flow through angiogenesis. In chronic phase, weekly multiple dosing of Epo induced angiogenesis, however, the blood flow ratio did not increase significantly. The results of this study suggest that Epo administration during the acute phase followed by maintenance for several days may be important for increasing blood flow and angiogenesis.


Assuntos
Eritropoetina/farmacologia , Membro Posterior/irrigação sanguínea , Isquemia/metabolismo , Doença Aguda , Animais , Doença Crônica , Isquemia/patologia , Fluxometria por Laser-Doppler , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Fisiológica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores da Eritropoetina/metabolismo , Proteínas Recombinantes/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Korean J Pathol ; 46(6): 541-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23323104

RESUMO

BACKGROUND: Clear cell papillary renal cell carcinoma (CCPRCC) is a recently established subtype of renal epithelial tumor. The aim of this study was to identify the diagnostic criteria of CCPRCC with an emphasis on immunohistochemical studies, and to report three cases with concurrent other-type renal cell carcinoma (RCC). METHODS: A total of 515 RCC patients that consecutively underwent surgical resection at Seoul National University Hospital from 1 January 2010 to 31 December 2011 were screened. Each case was reviewed based on the histologic features and was evaluated immunohistochemically. RESULTS: A total of 15 CCPRCCs were identified, which composed 2.9% of the total RCCs. The mean age was 52 years, and the average tumor size was 1.65 cm. All 15 cases showed low nuclear grade, no lymph node metastasis and no distant metastasis. The CCPRCCs showed variable architectural patterns including cystic, trabecular, papillary, and acinar. All of the cases showed moderate to intense immunoreactivity for cytokeratin 7 (CK7). CD10 was negative or showed focal weak positivity. Three cases had concurrent other-type RCC, including a clear cell RCC and an acquired cystic disease-associated RCC. CONCLUSIONS: The strong CK7 and negative or focal weak CD10 expression will be useful for the diagnosis of CCPRCC.

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