Cell blocks allow reliable evaluation of expression of basal (CK5/6) and luminal (CK8/18) cytokeratins and smooth muscle actin (SMA) in breast carcinoma

Objective:Gene expression studies have revealed several molecular subtypes of breast carcinoma with distinct clinical and biological behaviours. DNA microarray studies correlated with immunohistochemical profiling of breast carcinomas using cytokeratin (CK) markers, Her2/neu, oestrogen receptor (ER), and basal myoepithelial cell markers have identified five breast tumour subtypes: (i) luminal A (ER+; Her2/neu-), (ii) luminal B (ER+; Her2/neu+), (iii) Her2 overexpression (ER-; Her2/neu+), (iv) basal-like (ER-; Her2/neu-, CK5/6 and 14+), and (v) negative for all markers. Luminal carcinomas express cytokeratins in a luminal pattern (CK8/18), and the basal-like type expresses CK5/6 and CK14 or basal epithelial cell markers. CK5/6, CK8/18, and smooth muscle actin (SMA) expression were assessed in cell blocks and compared with expression in surgical specimens.Methods:Sixty-two cases of breast carcinoma diagnosed by fine needle aspiration cytology with cell blocks and available surgical specimens were included. Cell blocks containing at least 10 high-power fields each with at least 10 tumour cells and surgical specimens were immunostained for CK5/6, CK8/18 and SMA.Results:Percentage sensitivity, specificity, positive predictive value, negative predictive value and accuracy were, respectively, 77, 100, 100, 92 and 94 for CK5/6; 98, 66, 96, 80 and 95 for CK8/18; and 92, 96, 85, 98 and 95 for SMA.Conclusion:The identification of CK5/6, CK8/18 and SMA by immunohistochemistry in cell blocks can be a reliable method that yields results close to those obtained in surgical specimens, and can contribute to the classification of breast carcinomas with luminal and basal expression patterns, providing helpful information in the choice of treatment and in the evaluation of prognostic and predictive factors.

Imunoexpressão do c-erbB-2 nas lesões epiteliais proliferativas intraductais da mama de mulheres

OBJETIVOS: Alterações genéticas são relacionadas à gênese e progressão do câncer. Neoplasias de vários órgãos expressam o oncogene c-erbB-2. Nas proliferações intraductais da mama tem sido avaliado como fator de risco para o desenvolvimento de câncer. Foram avaliadas a imunoexpressão do c-erbB-2 em lesões epiteliais proliferativas intraductais e as possíveis correlações com características anatomopatológicas do carcinoma ductal in situ (CDIS). MÉTODOS: Foi utilizado material de arquivo, amostras teciduais fixadas em formalina e incluídas em blocos de parafina de 88 mulheres. Destas, 51 com CDIS e 37 com hiperplasia ductal sem atipias (HDT). A idade variou de 35 a 76 anos. Revisados todos os casos, verificou-se: o grau nuclear, a presença de necrose, o subtipo histológico predominante e sua extensão. Obteve-se material suficiente para o estudo imunohistoquímico do c-erbB-2 de 84 sujeitos do estudo. RESULTADOS: Não foi observada a expressão do oncogene nas hiperplasias sem atipias e nos tecidos adjacentes a todas amostras teciduais. A expressão do c-erbB-2 foi verificada em nove (19,1%) dos CDIS (p= 0,0001). A imunoexpressão não se relacionou à extensão das lesões. A imunoexpressão do c-erbB-2 no CDIS correlacionou-se com subtipo histológico (p=0,019), com a presença de necrose (p=0,0066), com o grau nuclear (p=0,0084) e com a Classificação de Van Nuys (p=0,039). CONCLUSÕES: A expressão do c-erbB-2 foi estatisticamente significante nas lesões proliferativas de risco (CDIS) e correlacionou-se com características histopatológicas: alto grau nuclear, presença de necrose, subtipo comedo. Não houve expressão nas hiperplasias sem atipias e tecidos adjacentes.

Carcinoma de Meibômio como segundo tumor em portadores de retinobastoma: relato de dois casos

O retinoblastoma pode acometer um ou os dois olhos, ocorrendo de forma hereditária ou esporádica. O portador dessa doença pode desenvolver, a longo prazo, outros tipos de tumores não oculares. Relatamos dois pacientes: o filho, portador de cavidade anoftálmica bilateral após remoção dos olhos devido ao retinoblastoma, que apresentou segundo tumor palpebral unilateral, afetando a pálpebra superior; e o pai, portador de cavidade anoftálmica unilateral também por remoção de retinoblastoma e que apresentou tumoração de crescimento rápido na pálpebra superior ipsilateral ao olho enucleado. O exame imuno-histoquímico de ambas as lesões excisadas revelou que se tratava de carcinoma de glândulas sebáceas. Os pacientes evoluíram bem após a remoção do tumor palpebral e, até o momento, não apresentam sinais de recidiva ou metástase.

Edema de Reinke: estudo da imunoexpressão da fibronectina, da laminina e do colágeno IV em 60 casos por meio de técnicas imunoistoquímicas

Edema de Reinke é doença crônica da laringe na qual a camada superficial da lâmina própria é expandida por muco espesso conferindo-lhe aspecto gelatinoso. Relaciona-se ao tabagismo e acomete, preferencialmente mulheres, as quais apresentam a voz mais grave. Suas características histológicas nem sempre conseguem diferenciá-lo das demais lesões benignas da laringe, havendo necessidade de técnicas histológicas adicionais. OBJETIVOS: Estudar a imunoexpressão da fibronectina, do colágeno IV e da laminina no edema de Reinke por meio de técnicas imunoistoquímicas. Estudo prospectivo. MATERIAL E MÉTODOS: Blocos histológicos de 60 casos cirúrgicos de edema de Reinke foram resgatados, submetidos a novos cortes e às reações imunoistoquímicas para fibronectina, laminina e colágeno IV pelo método da Avidina Biotina Peroxidase. Todos os pacientes eram fumantes e adultos, sendo 50 mulheres e 10 homens. RESULTADOS: As análises da imunoexpressão da fibronectina, do colágeno IV e da laminina foram mais expressivas no endotélio dos vasos (68,33%, 76,66%, 73,33%, respectivamente), e menos relevantes na membrana basal (25,0%, 5,0% e 3,3%, respectivamente). CONCLUSÕES: No edema de Reinke, a imunoexpressão da fibronectina, da laminina e do colágeno IV na membrana basal não apresentam relevância, havendo predomínio desses anticorpos no endotélio do vasos.

Matrix metalloproteinase-9 expression in pterygium

OBJETIVO: Avaliar a expressão da metaloprotease de matriz (MMP)-9 nos pterígios. MÉTODOS: Foi realizado na Faculdade de Medicina de Botucatu estudo prospectivo, aleatório, com o intuito de avaliar a expressão da metaloprotease de matriz na cápsula de Tenon normal e de pterígios primários e recidivados, usando o método da imuno-histoquímica e o sistema computadorizado de análise de imagem. Os resultados foram avaliados estatisticamente. RESULTADOS: A expressão da metaloprotease de matriz foi semelhante na cápsula de Tenon normal e nos pterígios primários e recidivados. CONCLUSÃO: A expressão da metaloprotease de matriz na cápsula de Tenon normal e nos pterígios primários ou recidivados é semelhante, o que nos leva a concluir que esta metaloprotease de matriz não esteja envolvida na gênese ou na recidiva do pterígio.

Human bcl-2 expression, cleaved caspase-3, and KSHV LANA-1 in Kaposi sarcoma lesions

We aimed to evaluate the frequency of Kaposi sarcoma (KS)-associated herpesvirus (KSHV) infection in KS lesions in patients from Brazil. In addition, expression of human bcl-2, cleaved caspase-3, and KSHV latency-associated nuclear antigen (LANA)-1 in tumors was evaluated using inummohistochemical analysis. We studied 64 KS cases, classified as follows: classical, 20 (31 %); iatrogenic, 2 (3 %); AIDS-associated, 25 (39%); and not otherwise specified (lack of information about HIV status), 17 (27%). KSHV was detected by polymerase chain reaction (PCR) in 61 cases (95%); 40 cases (63%) were KSHV+ by PCR and immunohistochemical analysis for LANA-L Immunoexpression of bcl-2 was detected in 47 cases (73%). Only a few cells in 15 cases (23%) of KS had demonstrable immunostaining for cleaved caspase-3. These results further support the association of KSHV with all KS forms. Cleaved caspase-3 in KS tumors was infrequent, which may reflect the inhibition of apoptosis owing to bcl-2 overexpression observed in the majority of KS tumors.

Immunohistochemistry of small blue round cell tumors

Small blue round cell tumors (SBRCTs) are a set of malignancies that have a particular proclivity for the pediatric age group. These tumors are notoriously difficult to distinguish by histologic evaluation alone, and in recent years a number of new immunohistochemical markers have emerged that can aid in the correct categorization of these lesions. Myogenin, a muscle-restricted nuclear transcription factor, has been demonstrated to be a highly sensitive and specific marker of rhabdomyosarcoma, and is superior to previous markers such as myoglobin, muscle actins, and desmin. The FlI-1 gene product is expressed as part of the EWS/FLI-1 novel chimeric protein that results from the t(11;22)(q24;q12) translocation that occurs in approximately two-thirds of cases of PNET/Ewings sarcoma. Immunohistochemical detection of the FLI-1 gene product can thus complement detection of CD99/MIC2 for the positive identification of PNET/Ewings sarcoma. Markers of neuroblastoma include neural markers, such as chromogranin A, neurofilaments, and synaptophysin. Desmoplastic small round cell tumor (DSRCT) is a tumor with an unusual immunophenotype, including co-expression of cytokeratin, vimentin, and desmin; recent studies have also documented the use of antibodies to the WT-1 gene product as a marker of the chimeric EWS/WT-1 protein formed as a result of the t(11;22)(p13;q12) translocation that characterizes this unique tumor. In summary, there now exists a panel of antibodies defining immunohistochemical markers of individual SBRCTs that can identify rhabdomyosarcoma, PNET/Ewings sarcoma, neuroblastoma, and DSRCT with high sensitivity and specificity.

Pseudoangiomatous hyperplasia of mammary stroma associated with gynaecomastia

Aims-To evaluate the prevalence of pseudoangiomatous hyperplasia of mammary stroma in gynaecomastia and its immunohistochemical profile in this setting.Methods-Eighty eight cases of gynaecomastia recovered from the files of the department of pathology, Botucatu School of Medicine from 1976 to 1996 were studied. In the cases associated with pseudoangiomatous hyperplasia of mammary stroma, immunoreactivity for cytokeratins (CAM 5.2), vimentin, CD34, factor VIII related antigen, and the oestrogen and progesterone receptors were studied.Results-Pseudoangiomatous hyperplasia of mammary stroma was found in 21 of 88 cases of gynaecomastia (23.8%). In all cases, the cells lining the spaces were positive for vimentin, whereas CAM 5.2 and factor VIII related antigen were consistently negative. Nineteen of the 21 cases showed immunoreactivity for CD34. Ductal epithelial cells were positive for both the oestrogen receptor and the progesterone receptor, whereas stromal cells were negative.Conclusions-Pseudoangiomatous hyperplasia of mammary stroma was present in approximately one quarter of the cases of gynaecomastia. This immunohistochemical study confirms the mesenchymal origin of the stromal cells that line the pseudovascular spaces, as has been found in female cases of pseudoangiomatous hyperplasia of mammary stroma.

Modifying Effects of Lemongrass Essential Oil on Specific Tissue Response to the Carcinogen N-Methyl-N-Nitrosurea in Female BALB/c Mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of Carcinogenic Potential of Diuron in a Rat Mammary Two-Stage Carcinogenesis Model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mate attenuates DNA damage and carcinogenesis induced by diethylnitrosamine and thermal injury in rat esophagus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Evaluation of estrogen receptor alpha and beta and progesterone receptor expression and correlation with clinicopathologic factors and proliferative marker Ki-67 in breast cancers

To elucidate the molecular profile of hormonal steroid receptor status, we analyzed ER-alpha, ER-beta, and PGR mRNA and protein expression in 80 breast carcinomas using reverse transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR, and immunohistochemical analysis. Qualitative analysis revealed positive expression of ER-alpha, ER-beta, and PGR mRNA in 48%, 59%, and 48% of the breast carcinomas, respectively. ER-alpha, ER-beta, and PGR transcript overexpression was observed in 51%, 0%, and 12% of the cases, respectively, whereas moderate or strong protein expression was detected in 68%, 78%, and 49% of the cases, respectively. Tumor grade was negatively correlated with transcript and protein levels of ER-alpha (P = .0169 and P = .0006, respectively) and PGR (P = .0034 and P = .0005, respectively). Similarly, proliferative index Ki-67 was negatively associated with transcript and protein levels of ER-alpha (P = .0006 and P < .0001, respectively) and PGR (P = .0258 and P =. 0005, respectively). These findings suggest that ER-alpha and PGR expression are associated with well-differentiated breast tumors and less directly related to cell proliferation. A significant statistical difference was observed between lymph node status and ER-beta protein expression (P = .0208). In ER-alpha-negative tumors, we detected a correlation between ER-beta protein expression and high levels of Ki-67. These data suggest that ER-beta could be a prognostic marker in human breast cancer. (C) 2008 Elsevier B.V. All rights reserved.

Perineural Invasion in Aggressive Skin Carcinomas of the Head and Neck

Introduction: Perineural invasion is a well-recognized form of cancer dissemination. However, it has been reported only in few papers concerning cutaneous carcinomas ( basal cell, BCC, and squamous cell, SCC). Moreover, the incidence is considered to be very low. Niazi and Lambert [Br J Plast Surg 1993; 46: 156-157] reported only 0.18% of perineural invasion among 3,355 BCCs. It is associated with high-risk subtypes, as morphea-like, as well as with an increased risk of local recurrence. No paper was found in the literature looking for perineural invasion in very aggressive skin cancers with skull base extension, with immunohistochemical analysis. Methods: This is a retrospective review, including 35 very advanced skin carcinomas with skull base invasion (24 BCCs and 11 SCCs, operated on at a single institution from 1982 to 2000). Representative slides were immunohistochemically evaluated with antiprotein S-100, in order to enhance nerve fibers and to detect perineural invasion. The results were compared to 34 controls with tumors with a good outcome, treated in the same time frame at the same Institution. Results: Twelve (50.0%) of the BCCs with skull base invasion had proven perineural invasion, as opposed to only 1 (4.6%) of the controls, and this difference was statistically significant (p < 0.001). Regarding SCCs, 7 aggressive tumors (63.6%) showed perineural invasion compared to only 1 (10.0%) of the controls, but this difference did not reach significance (p=0.08), due to the small number of cases. Conclusions: In this series, it was demonstrated that immunohistochemically detected perineural invasion was very prevalent in advanced skin carcinomas. In addition, it was statistically associated with extremely aggressive BCCs with skull base invasion. Copyright (c) 2008 S. Karger AG, Basel

Effects of lycopene, synbiotic and their association on early biomarkers of rat colon carcinogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Adenocarcinoma of the parotid salivary gland in a cow

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)