Identification of a subtype of poorly differentiated invasive ductal carcinoma of the breast based on vimentin and e-cadherin expression / Identificação de um subtipo pouco diferenciado de carcinoma ductal invasivo de mama, baseado na expressão da vimentina e E-caderina

Abstract Objective The use of molecular markers can identify a subgroup of tumors with distinct recurrence patterns. The present study aimed to characterize the immunohistochemical expression of vimentin (VIM), of E-cadherin (CDH1), and of cytokeratin 5 (CK5) in patients with invasive ductal carcinomas (IDCs). Methods We have constructed a tissuemicroarray (TMA) from87 patients with IDC of the breast. Immunohistochemistry (IHC) was performed to study the expression of estrogen and progesterone receptors (ER and PgR), human epidermal growth factor receptor 2 (HER2), VIM, CDH1, CK5, and Ki67. The tumors were classified as luminal A and B (n = 39), HER2 enriched (n = 25), and triple-negative (TNBC) (n = 23), based on the IHC expression. Results We have observed that luminal A and B tumors lack the VIM+/CDH1-/low phenotype. This phenotype was observed in 16.5% of the HER2+ tumors and in 60% of the TNBC tumors (p = 0.0001). Out of a total of 20 TNBC tumors, the CK5 (basal-like marker) was positive in 11 of them. The VIM+/CDH1-/low phenotype was observed in 5 CK5+ TNBC tumors (45%) and in 7 out of 9 CK5- TNBC tumors (78%) (p = 0.02). The median Ki67 index in the VIM+/CDH1-/low tumors was 13.6 (range: 17.8-45.4) compared with 9.8 (range: 4.1-38.1) in other tumors (p = 0.0007). The presence of lymph nodemetastasis was less frequent in patients with VIM+/CDH1-/low tumors (23% versus 61%; X2 test; p = 0.01). Conclusion Our findings suggest that the expression of VIM and CDH1 can identify a subset of IDCs of the breast with a mesenchymal phenotype associated with poor prognosis, high-grade lesion, and high mitotic index.

Resumo Objetivo O uso de marcadores moleculares pode identificar subtipos tumorais com diferentes taxas de recidiva. O objetivo do presente estudo é caracterizar a expressão imunohistoquímica da vimentina (VIM), da E-caderina (CDH1) e de CK5 em pacientes com carcinoma ductal invasivo (CDI) da mama. Métodos Utilizamos uma matriz de amostras teciduais (TMA, na sigla em inglês) de 87 pacientes com CDI da mama. Para avaliar a expressão dos receptores de estrogênio (RE) e receptores de progesterona (RP), HER2, VIM, CDH1, CK5 e Ki67, utilizamos imunohistoquímica. Os tumores foram classificados como luminal A e B (n = 39), HER2+ (n = 25) e triplo negativo (TNBC) (n = 23). Resultados Foi observado que tumores luminais A e B não expressaram o fenótipo VIM+/CDH1-/low. Este fenótipo foi observado em 16,5% dos tumores HER2+ e em 60% dos tumores TNBC (p = 0,0001). Dos 20 tumores TNBC, a CK5 (marcador de tumor basalóide) foi super expressa em 11 amostras. O fenótipo VIM+/CDH1-/low foi observado em 5 tumores CK5+ TNBC (45%) e em 7 dos 9 tumores CK5- TNBC (78%) (p = 0,02). A expressão média de Ki67 nos tumores VIM+/CDH1-/low foi 13.6 (amplitude de 17,8 a 45,4) comparado com 9,8 (amplitude de 4,1 a 38,1) nos outros tumores (p = 0,0007). A presença demetástase linfonodal foimenor em tumores com fenótipo VIM+/CDH1-/low (23% contra 61%; teste X2; p = 0,01). Conclusão Nossos achados sugerem que a expressão de VIM e CDH1 pode identificar um subtipo de CDI da mama com fenótipo mesenquimal associado a pior prognóstico, lesões de alto grau e alto índice mitótico.

p16INK4a protein is a specific molecular biomarker of breast cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of p16INK4a protein in breast cancer and analyze its clinical significance.</p><p><b>METHODS</b>A total of 132 surgical specimens of primary breast cancer obtained between 2014 and 2015 were examined for expressions of ER, PR, CK5/6, Her-2 and p16INK4a proteins using immunohistochemistry.</p><p><b>RESULTS</b>The breast cancer samples were classified into 5 molecular subtypes, namely Luminal A (58 cases), Luminal B (32 cases), Her-2-positive (21 cases), basal-like (12 cases) and normal-like (9 cases) types. p16INK4a expression was negative in 7/132 (5.30%) cases, weakly positive in 15/132 (11.36%) cases, positive in 40/132 (30.30%) cases, and strongly positive in 70/132 (53.03%) cases. When categorizing negative and weakly positive cases into negative group and the positive and strongly positive cases into positive group, the total negative and positive expression rates of p16INK4a were 16.67% (22/132) and 83.33% (110/132) in the carcinoma tissues. Statistical analysis showed the expression intensity of p16INK4a differed significantly between the age groups (P<0.05) but was not significantly correlated with ER, PR, Her-2, molecular subtypes or metastasis of the tumors.</p><p><b>CONCLUSION</b>The compensatory high expression of p16INK4a is the main mechanism of cell cycle deregulation in invasive breast cancer and can be an important specific molecular marker for invasive breast cancer.</p>

Expression of p63, p40 and CK5/6 in small cell lung cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of squamous cell markers p63, p40 and CK5/6 in small cell carcinoma of lung (SCLC).</p><p><b>METHODS</b>Immunohistochemical study for squamous cell markers (p63, p40 and CK5/6), neuroendocrine markers (chromogranin A, synaptophysin and CD56) and TTF1 was carried out in 283 cases of SCLC. The diagnostic value of these markers was evaluated.</p><p><b>RESULTS</b>The expression rate of p63, p40 and CK5/6 were 20.7% (54/261), 7.9% (5/63) and 0.5% (1/221), respectively in the cases of SCLC studied. Amongst the squamous cell markers, CK5/6 had the lowest rate of positivity (P < 0.01). On the other hand, chromogranin A, synaptophysin and CD56 were positive in 61.8% (170/275), 85.5% (242/283) and 89.2% (248/278), respectively. The positivity rate for chromogranin A was lower than that for synaptophysin and CD56 (P < 0.01). TTF1 was expressed in 77.2% (217/281).</p><p><b>CONCLUSIONS</b>p63 and p40 are expressed in a subset of SCLC. In contrast, CK5/6 is rarely positive in SCLC. An immunohistochemical panel of CK5/6, synaptophysin and CD56 is recommended for differential diagnosis of SCLC.</p>

Value of CK5/6, CK14, ER and PR detection in differential diagnosis of intraductal proliferative lesions of the breast / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of high-molecular-weight keratins CK5/6, CK14, estrogen receptor (ER) and progesterone receptor (PR) in differential diagnosis of simple ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH) and low-grade ductal carcinoma in situ (low-grade DCIS) .</p><p><b>METHODS</b>The clinicopathological data of twenty cases of atypical ductal epithelial hyperplasia (ADH) with focal cancerization changed into low-grade DCIS diagnosed at Tianjin Medical University Cancer Institute and Hospital between January 2013 and February 2014 were reviewed and analyzed. The expressions of CK5/6, CK14, ER and PR were detected by immunohistochemistry.</p><p><b>RESULTS</b>Positive expressions of CK5/6 and CK14 were seen in UDH showing a mosaic pattern, while negative expression in ADH and low-grade DCIS. In addition, CK5/6 and CK14 were positively expressed in the myoepithelial cells of UDH, ADH and low-grade DCIS. Positive expressions of ER and PR were observed in UDH, ADH and low-grade DCIS. But they presented diffuse and homogeneous strong positive expression in ADH and variable positive expression in UDH.</p><p><b>CONCLUSION</b>In the intraductal proliferative lesions of the breast, the use of combined detection of the expression of CK5/6, CK14, ER and PR is of practical significance in the differential diagnosis of UDH, ADH and low-grade DCIS.</p>

Clinicopathologic features of cystic hypersecretory lesion of the breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype and differential diagnosis of cystic hypersecretory lesion (CHL) of the breast.</p><p><b>METHODS</b>Clinicopathologic and follow-up data of six cases of breast CHL in 2010-2013 were collected and reviewed.Immunohistochemical and mucinous staining was performed.</p><p><b>RESULTS</b>All six patients were female, age ranged from 37 to 71 years (average 49.3 years). Three cases were cystic hypersecretory hyperplasia (CHH), the other three cases were cystic hypersecretory carcinoma (CHC). Clinically the lesions presented as either breast mass or mammographic calcification.Grossly, the cystic hypersecretory lesions were poorly circumscribed, with multiple colloid containing cysts on the cut surface. Microscopically, the remarkable feature was numerous enlarged cysts which contained densely eosinophilic homogeneous secretion similar to the colloid seen in thyroid follicles, and calcification was seen in the cyst in one case. The secretion was D-PAS and mucicarmine positive. The lining epithelium of the cysts was uniformly flat, cuboid or columnar, and arranged in a monolayer. The cells may be arranged in turfs, solid or micropapillary patterns in CHH.In cases with dysplasia, the epithelium showed cytological and structural atypia, but the usual morphology of atypical dutal hyperplasia such as arcades, rigid bridges or cribriform pattern was less common. The three CHC included two invasive ductal carcinomas (IDC) and one ductal carcinoma in situ (DCIS).In CHL, there was immunoreactivity to S-100 protein, CK5/6 and CK14.Of the three CHCs, ER and PR were expressed in only one IDC.No HER2 expression was identified in the two invasive CHCs.One patient was lost to follow-up, and the rest were uneventful at 18 months.</p><p><b>CONCLUSIONS</b>CHL of the breast is a rare pathological entity. Multiple colloid-filled cysts is a unique histological feature. The epithelium of CHL may show usual hyperplasia, dysplasia or carcinoma.</p>

Weber-Cockayne Type Epidermolysis Bullosa Simplex Resulting from a Novel Mutation (c. 608T>C) in the Keratin 5 Gene

Epidermolysis bullosa simplex (EBS), an inherited genetic disorder, is most often caused by a dominant-negative mutation in either the keratin 5 (KRT5) or the keratin 14 (KRT14) gene. These keratin mutants result in a weakened cytoskeleton and cause extensive cytolysis. It is important to analyze the KRT5 or KRT14 genes of the patient and their family members by mutational analysis in order to identify genetic defects as well as the need for genetic counseling. In this study, we present a 5-year-old Korean boy who had been developing blisters and erosions on the palms of his hands and soles of his feet since infancy. In addition, while his younger sister and father showed similar clinical manifestation, his mother did not. The patient was diagnosed with EBS based on clinical manifestation, which is characterized by the presence of blisters restricted to the palms and soles, histological findings, and mutational analysis. Mutational analysis of the patient's DNA revealed a thymine-to-cytosine transition at codon 608 in the KRT-5 gene, resulting in a leucine-to-proline substitution in the keratin 5 protein. The same mutation was identified in the paternal, but not maternal, DNA. Here, we report a case of Weber-Cockayne type EBS with vesicles and bullae restricted to the palms and soles with a novel, paternally inherited mutation in KRT5 gene (exon2, c.608T>C).

Basaloid Squamous Cell Carcinoma Manifested as a Solitary Erythematous Nodule / 대한피부과학회지

Basaloid squamous cell carcinoma (BSCC) is a rare malignancy, which has a predilection for the upper aerodigestive tract. A 78-year-old man presented with solitary erythematous nodule on the right neck. The tumor mass was rapidly enlarged for last 5 months and firmly attached to deep soft tissue. Neck computed tomography showed enhanced density in vallecular region and enlarged cervical lymph nodes. Wide excision of the tongue base with modified lymph node dissection, including the solitary erythematous nodule, was performed. Histopathologically, the tongue base and cutaneous lesion displayed closely packed basaloid cells with comedonecrosis and squamous eddy formation. The cells demonstrate a high nuclear to cytoplasmic ratio and abundant mitotic figures. Staining for p63, cytokeratin 5 (CK5) demonstrated diffuse uptake within the tumor and CD56 stain was negative. We diagnosed this case as the first Korean case of metastatic cutaneous BSCC.

Value of T cell receptor gamma alternate reading frame protein and keratin 5 in endometrial carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tumors with different gene expression develop and progress in different ways. To deepen our understanding of the progression in endometrial cancer, and provide a useful tool for accurate diagnosis and prognosis assessment, we identified the new molecular prognostic markers in endometrial carcinoma and analyzed the relationship of them with clinical and pathological features of endometrial carcinoma.</p><p><b>METHODS</b>Ninety-four cases of endometrial endometrioid adenocarcinoma with complete data from the Peking University People's Hospital from 2000 to 2008 and 40 cases of normal endometrium were enrolled. Among these, 30 endometrial endometrioid adenocarcinoma samples of different International Federation of Gynecology and Obstetrics (FIGO) stage were selected for further Agilent genome-wide microarray analysis. Significance analysis of microarrays (SAM) was used to identify genes that are significantly associated with tumor progress. Immunohistochemistry was utilized to identify the genes of interest in endometrial carcinoma and normal endometrium. The relationship between the genes and the age, clinical stage, histological grade, myometrium invaded depth, lymph node metastasis status, and the expression of ER, PR, P53, and PTEN were analyzed by χ(2) test.</p><p><b>RESULTS</b>Analysis between FIGO 1988 stage I and stage III identified a 362-gene "progress signature"; 171 down-regulated and 191 up-regulated genes. Among the alterative genes, TARP (T cell receptor gamma alternate reading frame protein) and KRT5 (keratin 5) decreased 3.57 fold and 5.8 fold in FIGO stage III patients. The expression of TARP in endometrial carcinoma increased compared to normal endometrium, while that of KRT5 decreased (P < 0.05). The expression of TARP and KRT5 decreased when stage, histological grading, myometrium invaded depth increased (P < 0.05). In the cases with lymph node metastasis, the expression of TARP decreased, while the expression of KRT5 did not differ (both P < 0.05) both. The expression of P53 had a negative relationship with the expression of KRT5 (P < 0.05), but not with the expression of TARP (P > 0.05). There was no correlation between the expression of TARP and KRT5 and the expression of ER, PR, PTEN (all P > 0.05). There was no significant difference in TARP and KRT5 expression in patients aged 50 or younger and patients older than 50 (P > 0.05).</p><p><b>CONCLUSION</b>The expression of TARP and KRT5 was correlated with the progress of endometrial cancer and their role needs further study.</p>

Clinicopathologic features and immunohistochemistry of the basal-like subtype of invasive breast carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features and immunohistochemical of the basal-like subtype of invasive breast carcinoma (BLBC), and to discuss the diagnosis standard.</p><p><b>METHODS</b>Immunohistochemistry was performed in 448 cases of breast carcinoma and these cases were categorized into luminal A, luminal B, null subtypes, HER2-overexpressing and basal-like and their clinicopathologic features were observed under light microscope with stains of HE and immunohistochemical InVitrogen staining.</p><p><b>RESULTS</b>Among the breast cancer patients, the incidence of BLBC was 15.4% (69/448). Morphologic features significantly associated with BLBC constituently included nest structure and showing diffuse growth pattern, large scarring areas without cells in tumor, geographic necrosis, pushing margin of invasion, lymphocytic infiltrate in various degree in tumor stroma, syncytial tumor cell without clear boundaries, tumor cell showing vesicular unclear chromatin and nucleolus, markedly elevated mitotic count, metaplasia (all P < 0.01). Meanwhile, most BLBC showed strong immunoreactivity for CK5/6, CK14, CK17 (all P < 0.01).</p><p><b>CONCLUSION</b>BLBC showed distinct morphologic and immunophenotypic features.</p>

Mechanism of psoriasis generation in animal models / 药学学报

Psoriasis is a chronic inflammatory disease related to genome-wide and surroundings, it is important to develop a suitable animal model to research psoriasis pathogenesis and evolve pharmacotherapeutics. With the development of transgenetic technology in the past few years, psoriasis virulence gene animal model become a hotspot. Research of animal model of human psoriasis genes is reviewed in the paper.

Invasive lobular carcinoma of basal-like subtype of breast: a clinicopathologic analysis / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features, clinical progress and prognosis of the basal-like subtype of invasive lobular carcinoma (ILC) of the breast.</p><p><b>METHODS</b>Four cases of ILC were analyzed by detailed histopathologic observation and immunohistochemical staining for E-cadherin, p120 catenin, ER, PR, HER2, CK5/6, EGFR, p63, p53, Ki-67 using MaxVision method. The follow-up and clinical data were analyzed.</p><p><b>RESULTS</b>Morphologically, one case was mixed ILC and three cases were pleomorphic ILC. The tumor cells were negative for E-cadherin except one case with focal membrane positivity, and all showed p120 catenin cytoplasmic positivity except one case with focal membrane positivity. All cases were negative for ER, PR and HER2 (triple negative), and positive for EGFR and CK5/6. Two cases were positive for p63. The cases were partly and weakly positive for p53, and the Ki-67 positive rate was between 30% and 75%. Follow-up data showed that two cases developed chest wall metastases, and in one case, there was progression to liver and abdominal metastases.</p><p><b>CONCLUSIONS</b>ILC of the breast are ER, PR and HER2 "triple negative", CK5/6 and EGFR positive, indicative of basal-like characteristics. Basal-like subtype of ILC are peculiarly prone to metastasis and poor response to chemotherapy, suggesting that it is associated with poor prognosis.</p>

A Case of Epidermolysis Bullosa Simplex (Other Generalized Type) / 대한피부과학회지

The other generalized type of epidermolysis bullosa simplex (EBS) is a genetic blistering skin disease, caused by a mutation of the genes encoding keratin 5 and 14. EBS starts at birth and is characterized by generalized blisters following a minor trauma that heals with hyperpigmentation. A 19-year-old man presented with 19-year history of multiple erythematous vesicles in a herpetiform arrangement on the trunk, axilla, and thigh with post-inflammatory hyper-pigmentations. On light and electron microscopy, the biopsy specimen showed intraepidermal blisters that formed within the basal keratinocyte. The serum from a patient with bullous pemphigoid antibody and laminin 5 antibody showed the linear deposition at the floor of the blister on immunofluorescence mapping study. On the basis of our clinical, microscopic, and immunofluorescence findings, we diagnosed the patient as having a generalized type of EBS. Herein, we report on an interesting case of the other generalized type of EBS.

Pathologic diagnosis and differential diagnosis of low-grade adenosquamous carcinoma of breast and syringomatous adenoma of nipple / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the pathologic and immunohistochemical features, diagnosis and differential diagnosis of low-grade adenosquamous carcinoma of the breast and syringomatous adenoma of the nipple.</p><p><b>METHODS</b>Six cases of low-grade adenosquamous carcinoma of the breast and four cases of syringomatous adenoma of the nipple were examined histologically and immunohistochemically (MaxVision method), and the literature was reviewed.</p><p><b>RESULTS</b>The two types of tumors were similar in morphology, but located in different regions with low-grade adenosquamous carcinoma being present in the deep parenchyma and syringomatous adenoma in nipple. Both types of tumors were composed mainly of well-differentiated glands with angulated, comma shaped or polliwog appearance in a disordered infiltrative pattern. The tumor cells also formed solid tubules, strips or nests, with frequent areas of squamoid differentiation. Mitosis was rare. The interstitial tissue showed abundant spindle cells or sclerotic fibrosis with mixed inflammatory cells infiltration. One case of low-grade adenosquamous carcinoma showed a concomitant malignant adenomyoepithelioma, and another case showed concomitant spindle cell metaplastic carcinoma. One case of syringomatous adenoma involved the deep parenchyma. Immunohistochemistry of low-grade adenosquamous carcinoma showed that CK5/6 and p63 were positive in the outer layer of the glands and the squamoid epithelium, and CD10 was also positive in the outer layer of the glands. ER and HER2 were negative, and PR was also negative except for one case in which the spindle cells were positive for CK5/6, AE1/AE3 and PR focally. Immunostaining of syringomatous adenoma demonstrated that p63 and CK5/6 were positive in the outer layer of the glands and the squamoid epithelium. Calponin, SMA, ER, PR and HER2 were all negative.</p><p><b>CONCLUSIONS</b>Low-grade adenosquamous carcinoma of the breast and syringomatous adenoma of the nipple are similar in morphology and immunohistochemical phenotype, while the biological features are opposite due to different locations. The differential diagnoses include tubular carcinoma, adenosquamous carcinoma, radial sclerosing lesions and others.</p>

Solid variant of mammary adenoid cystic carcinoma with basaloid features: a clinicopathologic and immunohistochemical study / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic and immunohistochemical features as well as the differential diagnoses of the solid variant of mammary adenoid cystic carcinoma with basaloid features.</p><p><b>METHODS</b>Clinical and pathological data were collected in four cases of the solid variant of mammary adenoid cystic carcinoma with basaloid features, and microscopic pathological examination and immunohistochemistry EnVision method were performed. The relevant literature was also reviewed.</p><p><b>RESULTS</b>The four patients were female, with age ranged from 46 - 65 years old (average 56 years) and the maximum tumor diameter ranged from 1.5 to 2.5 cm. Microscopically, the tumors exhibited a predominantly solid architecture with a myxoid or hyalinized stroma. The tumor cells showed moderate to marked nuclear atypia, and a basaloid appearance with scanty cytoplasm and inconspicuous nucleoli, and ≥ 5 mitotic figures per 10 high power fields. Glandular space embedded within tumor islands could be noticed. These spaces were genuine glandular structures and the cells lining these true glandular lumens had more abundant and eosinophilic cytoplasm. Pseudoglandular spaces of cribriform pattern or variable shape were also occasionally seen, and these cysts contained homogenous eosinophilic material. Focal necrosis was found. All cases were negative for ER, PR and HER2. Immunohistochemical staining for CK5/6, CK7 and CK14 was positive in the genuine glandular structures. All cases were positive for CD10, but also positive with varying intensity from weak to strong for vimentin and CD117. Staining for Ki-67 in three patients showed 10% - 50% positive.</p><p><b>CONCLUSIONS</b>The solid variant of mammary adenoid cystic carcinoma with basaloid features is a histologically distinctive and also a rare subset of the mammary adenoid cystic carcinoma. Awareness of its pathological features can help with the diagnosis as well as differential diagnosis. More cases are still needed for accurately assessing the prognosis of this particular tumor.</p>

Histologic morphology and involucrin, filaggrin, and keratin expression in normal canine skin from dogs of different breeds and coat types

The purpose of this study was to measure the thickness of canine epidermis at various anatomical sites according to localization of cornified envelopes (involucrin and filaggrin), keratins (keratin 10, 5), and their mRNA expression. This was done in the skin of five breeds of dogs including seven poodles, six golden retrievers, six Shih Tzus, four pugs, and four Labrador retrievers. Epidermal thickness of the stratum corneum and nucleated epidermal layer was significantly different. The greatest thickness was observed in the digital web area and the thinnest epidermis was in the axilla. Epidermal thickness was also significantly different between the breeds (p < 0.05). Immunohistochemical staining scores revealed significant decreases of involucrin, filaggrin, and keratin 10 in the ventral and weight-bearing sites, and a relative increase of keratin 5 (p < 0.05). q-PCR analysis showed that their the levels of mRNA were positively correlated with expression of the corresponding proteins in skin samples (p < 0.05). The present study is the first to report the relationship between epidermal gene expression and histologic morphology of the skin in normal dogs. Further studies will be essential to fully understand the pathogenesis of skin barrier dysfunctions in canines.

Clinicopathologic features of endolymphatic sac tumor at cerebellopontine angle / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and immunophenotype of endolymphatic sac tumor (ELST) and normal endolymphatic sac.</p><p><b>METHODS</b>The clinical and histologic features were evaluated in 5 cases of ELST. Eight cases of choroid plexus papilloma at cerebellopontine angle and 2 cases of normal endolymphatic sac were used as controls. Immunohistochemical study for vimentin, AE1/AE3, CK8/18, CK5/6, EMA, GFAP, synaptophysin, S-100 protein, CEA, TTF-1, VEGF, D2-40, calponin, calretinin and Ki-67 was carried out.</p><p><b>RESULTS</b>The age of onset of ELST ranged from 23 to 35 years (median = 24 years). The male-to-female ratio was 2:3. The clinical presentation was tinnitus, otalgia, hearing loss, otorrhagia with effusion and headache. The duration of symptoms ranged from 6 months to 10 years. Local recurrences were noted in 3 cases. Radiologically, the tumors were located at cerebellopontine angle and demonstrated petrous bone destruction. Histologic examination showed that the tumors had a papillary-glandular pattern. The papillae were covered by a single layer of low cuboidal cells. The tumor cells had distinct cell borders and contained eosinophilic to clear cytoplasm. The nuclei were slightly atypical and sometimes apically located. Focal dilated glandular structures with colloid-like material were also identified. The surrounding stroma was vascularized. All of the 5 cases had dural or petrous bone infiltration. Immunohistochemical study showed that all of the 5 cases were positive for AE1/AE3, CK8/18, CK5/6 and VEGF, 4 cases for EMA, 3 cases for calponin (focal), 2 cases for vimentin, 2 cases for S-100 protein, 1 case for GFAP and 1 case for synaptophysin (focal and weak). The Ki-67 index measured less than 1%. The staining for D2-40, calretinin, CEA and TTF-1 was negative. The 2 cases of the normal endolymphatic sac were positive for AE1/AE3 and CK8/18, and negative for CK5/6, EMA, S-100 protein, GFAP and synaptophysin. The 8 cases of choroid plexus papilloma were positive for synaptophysin. Seven cases were also positive for S-100 protein, 2 cases for GFAP and 1 case for D2-40. All of the 8 cases were negative for EMA, CK5/6 and calponin.</p><p><b>CONCLUSIONS</b>ELST is a rare slow-growing and potentially malignant tumor with a tendency of bone invasion and local recurrence. Distant metastasis is not observed. It must be distinguished from choroid plexus papilloma occurring at cerebellopontine angle. Correlation with clinical, radiologic and immunohistochemical findings would also be helpful.</p>

Clinicopathologic and immunohistochemical study of 187 cases of intraductal papillary neoplasm of breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the diagnostic approach and criteria for intraductal papillary neoplasms of breast.</p><p><b>METHODS</b>According to the criteria of 2003 WHO classification, 187 cases of intraductal papillary neoplasm of breast were identified and enrolled into the study. The clinical and histologic features were reviewed and immunohistochemical study for CD10, p63, CK14, CK5/6, CK7, MGB1 and p53 were carried out on 53 cases.</p><p><b>RESULTS</b>Amongst the 187 cases studied, there were 128 cases of intraductal papilloma, 16 cases of atypical intraductal papilloma and 43 cases of intraductal papillary carcinoma. They showed a spectrum of morphologic features including epithelial and stromal hyperplasia and secondary changes. The expression of myoepithelial markers, including CD10 and p63, significantly decreased in ascending order from intraductal papillomas, atypical intraductal papillomas and intraductal papillary carcinomas (P < 0.001). The expression of basal cell markers, including CK5/6 and CK14, showed a mosaic pattern in benign lesions and significantly decreased or was absent in atypical and carcinomatous lesions (P < 0.001). In contrast, the luminal cell marker CK7 expressed in the three groups with no statistically significant difference (P = 0.06). On the other hand, the expression of MGB1 in intraductal papillary carcinomas was much lower than that in the other two groups (P = 0.002 and P = 0.007). The staining for p53 was negative in all of the three groups.</p><p><b>CONCLUSIONS</b>Intraductal papillary neoplasms of breast represent a heterogeneous group of lesions with various morphologic appearances. Correlation with immunostaining results for myoepithelial markers, basal-type cytokeratins and luminal epithelial markers are helpful in arriving at a definitive diagnosis.</p>

Mutation analysis of keratin 5 and keratin 14 genes in a family with epidermolysis bullosa simplex with mottled pigmentation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify keratin 5 (K5) and keratin 14 (K14) gene mutations in a family affected with epidermolysis bullosa simplex with mottled pigmentation.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples obtained from eleven patients from the family and controls. All the exons of K5 and K14 genes were amplified using polymerase chain reaction (PCR) and directly sequenced.</p><p><b>RESULTS</b>By DNA sequence analysis, a missense mutation in K5 gene (c.237C>T) was detected. The same mutation was not found in non-affected members from the family and normal controls.</p><p><b>CONCLUSION</b>Mutation in K5 gene (c.237C>T) may be responsible for the development of disease in this family.</p>

Clinicopathlogic and Immunohistochemical Characteristics of Triple Negative Invasive Lobular Carcinoma

PURPOSE: Our study is performed to find out clinicopathlogic and immunohistochemical (IHC) characteristics of triple negative invasive lobular carcinoma (ILC), as has been demonstrated in their invasive ductal counterparts. MATERIALS AND METHODS: Retrospective analysis of variable clinicopathlogic parameters and IHC stains for androgen receptor, estrogen receptor, progesterone receptor, p53, c-kit, galectin-3, cytokeratin 5 (CK5), CK5/6, vimentin, E-cadherin, epidermal growth factor receptor, and HER2 were performed in 117 cases of ILC. RESULTS: Eight cases (6.8%) were triple negative carcinoma (TNC), which showed higher incidence of high histologic grade than non-TNC (p = 0.019). Galectin-3 was expressed with higher incidence in tumor cells of TNC (62.5%) than those of non-TNC (7.3%) (p = 0.000). In contrast, galectin-3 was expressed with higher incidence in stromal cells of non-TNC (53.2%) than those of TNC (12.5%) (p = 0.029). CK5 and CK5/6 were not expressed in all ILCs. CONCLUSION: TNC in ILC showed distinct clinicopathologic and IHC characteristics such as higher histologic grade and increased expression of galectin-3, compared to non-TNC in ILC. TNC in ILC was less frequent and did not show CK5 and CK5/6 expression when compared to TNC in invasive ductal carcinoma.

Relationship between breast cancer molecular subtypes with clinicopathological characteristics and prognosis / 中华病理学杂志

<p><b>OBJECTIVES</b>This study try to subclassify breast cancer into different prognostic subgroups according to immunohistochemical algorithm and discuss the relationship between subtypes and biological and clinical behavior and prognosis.</p><p><b>METHODS</b>One hundred and twenty-eight cases of infiltrative ductal carcinoma were studied using immunohistochemical staining with an antibody panel of ER, PR, HER2 and CK5/6 and subclassified referring to previous reports, and the 9 cases of HER2 positive subtype were tested using FISH.</p><p><b>RESULTS</b>The expression of ER, PR, HER2, and CK5/6 was detected in 67%, 45%, 27% and 27% cases, respectively. All cases were subclassified into five subgroups, with luminal A (55%), luminal B (20%), HER2 positive (7%), basal-like (10%) and unclassified cases (8%). Nine HER2 positive cases all showed amplification of HER2 gene. It was demonstrated that the luminal A group was associated with the best prognosis but the basal-like group worst by univariate analysis. Multivariate analysis demonstrated that both the clinical stage and immunohistochemical subtypes of tumor were related to overall survival. Menses status were different among these subtypes.</p><p><b>CONCLUSION</b>According to the expression of ER, PR, HER2 and CK5/6, infiltrative ductal carcinoma could be subclassified into five subgroups with different biological features and outcome, having a role in evaluating the prognosis and guiding the clinical treatment.</p>