ANDROGEN RECEPTOR EXPRESSION IN TRIPLE NEGATIVE BREAST CANCER AND ITS RELATIONSHIP TO PROGNOSTIC FACTORS / Expressão de receptor de androgênio em câncer de mama triplo negativo e sua relação com fatores prognósticos

Objective: Triple negative breast cancer (TNBC) is a subset of tumors with an aggressive intrinsic biology, resulting in poor prognosis. Androgen receptor (AR) is currently one of the most studied biomarkers in TNBC, playing a role in the genesis and development of breast cancer. Methods: In this cross-sectional study, we retrospectively reviewed the medical records of all patients with TNBC who received care from 2012 to 2014 at a single health center in southern Brazil. Histological material from breast tumors was analyzed by immunohistochemistry for AR expression and related to age, histological grade, tumor-infiltrating lymphocytes (TILs), and Ki-67. Results: Of 34 TNBC cases identified, 23 (67.6%) were AR negative and 11 (32.4%) were AR positive. The average age of the patients was 51.9 years (range: 30­82 years). Among positive cases, AR was weakly expressed in 6 and strongly expressed in 5 cases. Most patients (n=28; 82.0%) had poorly differentiated tumors. Mean Ki-67 expression was 65.0% in AR-negative and 43.6% in AR-positive cases (p<0.05). There was a significant association between age and AR expression (p<0.005), which was associated with mean age 70.8 years in the strongly AR-positive group and 42.3 years in the weakly AR-positive group. The mean percentage of TILs was 38.6% in AR-positive and 39.1% in AR-negative cases (p=0.391). Conclusion: There was no significant association between AR expression and histological grade or TILs. AR positivity in TNBC was associated with older age and tumors with lower Ki-67 expression, indicating two subgroups with distinct phenotypes in patients with TNBC.

Objetivo: O câncer de mama negativo triplo (triple negative breast cancer ­ TNBC) é um subtipo de tumores com biologia intrínseca agressiva, resultando em pior prognóstico. O receptor de andrógeno (androgen receptor ­ AR) é atualmente um dos biomarcadores mais estudados em TNBC, desempenhando papel na gênese e no desenvolvimento do câncer de mama. Métodos: Neste estudo transversal, revisamos retrospectivamente os registros médicos de todos os pacientes com TNBC que receberam atendimento de 2012 a 2014 em um único centro no sul do Brasil. O material histológico dos tumores de mama foi analisado por imuno-histoquímica para a expressão de AR e relacionado a idade, grau histológico, linfócitos infiltrantes de tumores (TILs) e Ki-67. Resultados: Dos 34 casos identificados de TNBC, 23 (67,6%) eram AR negativos e 11 (32,4%), AR positivos. A idade média foi de 51,9 anos (30­82 anos). Entre os casos positivos, AR foi fracamente expresso em 6 e fortemente expresso em 5 casos. A maioria dos pacientes (n=28, 82,0%) apresentou tumores pouco diferenciados. A expressão média de Ki-67 foi de 65,0% em AR-negativo e 43,6% em AR-positivo (p<0,05). Houve associação significativa entre a idade e a expressão de AR (p<0,005), associada à idade média de 70,8 anos no grupo com AR fortemente positivo e de 42,3 anos no grupo com AR fracamente positivo. A porcentagem média de TILs foi de 38,6% em AR-positivo e de 39,1% em AR-negativo (p=0,391). Não houve associação significativa entre expressão AR e grau histológico ou TILs. Conclusão: A positividade de AR em TNBC foi associada com idade mais avançada e tumores com menor expressão de Ki-67, indicando dois subgrupos com fenótipos distintos em pacientes com TNBC.

Expression analysis of transglutaminase 2 in premalignant lesions of the cervix

Background: The medical management of low-grade squamous intraepithelial lesions (LSIL) is variable, thus a biomarker could assist with the clinical conduct. Type 2 transglutaminase (TG2) has been proposed as a cellular-interfering factor in HPV infection and carcinogenesis. Therefore, this study has the objective of evaluating TG2 expression in LSIL and highgrade squamous intraepithelial lesions (HSIL) and of relating it to the different HPV viral types. Methods: This study included 146 patients with suspected LSIL or HSIL detected in routine conventional Papanicolaou tests. The presence of HPV DNA and viral typing was defined by the polymerase chain reaction method (PCR). TG2 Immunohistochemistry (IHC) was conducted according to the manufacturer's instructions; IHC was carried out in an Autosteiner-Link 48 Dako equipment. IHC quantitation was performed by relative expression and by using the software Image J. Qualitative variables, such as frequencies and proportions, were compared by using the χ2 test for independent samples. For comparison of the qualitative to the quantitative data, nonparametric Mann-Whitney test was used. Results: The association between histopathological examination and TG2 was statistically significant (p <0.05). Results showed that patients with normal cervical histopathology and LSIL are locally associated with TG2 expression levels >50% (p <0.05), and patients with HSIL are associated with no TG2 expression (p <0.05). The analysis of the samples with the Image J software shows a significant (p <0,001) decrease in TG2 immunostaining in HSIL if compared to normal and to LSIL samples. This demonstrates a correlation between the relative quantification and the results provided by Image J. Analysis of HPV types showed a significant association with HPV11 (p = 0.031). This indicates that patients with HPV type 11 had higher TG2 values than patients with different types. Image J analysis showed no significant association between TG2 and HPV viral types. Conclusion: The present data suggest that TG 2 has a high expression in LSIL and normal tissues, and decreased in HSIL. We also observed that its expression is associated with HPV11 (AU)

Leiomioma atípico / Atypical leiomyoma

Os autores relatam o caso de um leiomioma atípico ocasionalmente identificado em uma mulher de 45 anos submetida a histerectomia por sangramento uterino anormal. O leiomioma atípico, também conhecido como leiomioma bizarro ou simplástico, é um tumor pouco comum, sendo responsável por 0,5% a 1,0% das neoplasias mesenquimais uterinas. É caracterizado pela presença de células gigantes com múltiplos núcleos pleomórficos e cromatina grumosa. O seu comportamento biológico depende do seu índex mitótico e da presença de necrose tumoral. Paralelamente ao relato do caso, são discutidos os achados histopatológicos e clínicos do leiomioma atípico e a importância do seu diagnóstico diferencial com neoplasias malignas uterinas como o leiomiossarcoma.

The authors report a case of atypical leiomyoma occasionally identified in a woman of 45 who underwent hysterectomy for abnormal uterine bleeding. Atypical leiomyoma, also known as symplastic or bizarre leiomyoma, is an uncommon tumor accounting for 0.5-1.0% of uterine mesenchymal neoplasms. It is characterized by the presence of giant cells with multiple pleomorphic nuclei and granular chromatin. Its biological behavior depends on their mitotic index and the presence of tumor necrosis. Parallel to the case report we discuss the clinical and histopathological findings of atypical leiomyoma and the importance of its differential diagnosis with malignant uterine neoplasms such as leiomyosarcoma.

Alterações histopatológicas em placentas humanas relacionadas às síndromes hipertensivas / Histopathological changes in human placentas related to hypertensive disorders

OBJETIVO: determinar a prevalência de alterações histopatológicas em placentas humanas, relacionadas às síndromes hipertensivas. MÉTODOS: estudo de corte transversal, que comparou as alterações histopatológicas identificadas em 43 placentas oriundas de gestantes do grupo de hipertensas (GrHip) com as de 33 placentas de gestantes do grupo de normotensas (GrNor). Foram analisados o peso, volume e ocorrência macro e microscópica de infartos, coágulos, hematomas, aterose (obliteração parcial, espessamento de camadas e presença de vasos hialinizados) e alterações de Tenney-Parker (ausentes, discretas e proeminentes), bem como a localização de infartos e coágulos (central, periférico ou associação de ambos). Para a análise estatística foram usados os testes do χ2 e t de Student, bem como médias, desvios padrões e percentuais. Considerou-se como significante um p<0,05. RESULTADOS: o estudo macroscópico revelou que as placentas do GrHip, se comparadas às do GrNor, apresentaram menor peso (461,1 versus 572,1 g) e volume (437,4 versus 542,0 cm³) e percentuais aumentados de infartos (51,2 versus 45,5 por cento; p<0,05; OR=1,15) e de coágulos (51,2 versus 15,1 por cento; p<0,05; OR=5,4). Nos GrHip e GrNor, os infartos microscópicos ocorreram em 83,7 e 45,5 por cento; p<0,05; OR=4,3, respectivamente. A aterose e as alterações de Tenney-Parker associaram-se estatisticamente às síndromes hipertensivas (p<0,05). CONCLUSÕES: os dados obtidos permitem associar menor peso e volume placentário, maior percentual de infartos macro e microscópicos, coágulos, aterose e alterações de Tenney-Parker às placentas relacionadas com gestações que cursaram com síndromes hipertensivas.

PURPOSE: to determine the prevalence of histopathological changes, in human placentas, related to hypertensive syndromes. METHODS: a transversal study that compares histopathological changes identified in 43 placentae from hypertensive pregnant women (HypPr), with the ones from 33 placentae from normotensive pregnant women (NorPr). The weight, volume and macroscopic and microscopic occurrence of infarctions, clots, hematomas, atherosis (partial obliteration, thickness of layers and presence of blood vessels hyalinization) and Tenney-Parker changes (absent, discreet and prominent), as well as the locating of infarctions and clots (central, peripheral or the association of both) have been analyzed. The χ2 and t Student tests have been used for the statistical analysis, as well as medians, standard deviations and ratios. It has been considered as significant, p<0.05. RESULTS: the macroscopic study of HypPr placentae have presented lower weight (461.1 versus 572.1 g) and volume (437.4 versus 542.0 cm³), higher infarction (51.2 versus 45.5 percent; p<0.05: OR=1.15) and clots (51.2 versus 15.1 percent; p<0.05; OR=5.4) ratios, as compared to the NorPr's. In the HypPr and NorPr, microscopic clots have occurred in 83.7 versus 45.5 percent (p<0.05; OR=4.3), respectively. Atherosis and Tenney-Parker changes have been statistically associated to the hypertensive syndromes (p<0.05). CONCLUSIONS: the obtained data allow us to associate lower placentary weight and volume, higher ratio of macro and microscopic infarction, clots, atherosis and Tenney-Parker changes to placentae of gestations occurring with hypertensive syndromes.