ObjectiveTo evaluate the diagnostic and prognostic value of the immunohistochemical expression of WT1, p53 and p16 in low- (LGSOCs) and high-grade serous ovarian carcinomas (HGSOCs).ResultsHGSOC had a significantly higher proportion of advanced stage disease, higher CA125 levels, higher proportion of post-surgery residual disease and higher recurrence or disease progression. WT1 was expressed in 71.4% of LGSOCs and in 57.1% of HGSOCs (p = 0.32). Focal and/or complete absence of p53 expression with negative p16 expression was found in 90.5% of LGSOCs, in contrast to the 88.1% of HGSOCs with diffuse or complete absence of p53 expression with positive p16 expression (<0.001). The IHC p53/p16 index and the morphological classification were closely matched (k = 0.68). In the univariate analysis, FIGO stage, post-surgery residual disease and histological grade were significantly associated with progression-free survival (PFS) and overall survival (OS). The IHC p53/p16 index was associated only with PFS. WT1 was not associated with PFS or OS. According to the multivariate analysis, advanced FIGO stage and presence of post-surgery residual disease remained independent prognostic factors for worst PFS, however these features had only a trend association with OS.Methods21 LGSOC and 85 HGSOC stage I–IV cases were included. The morphological classification was assessed according to the World Health Organization (WHO) criteria. Immunohistochemistry (IHC) was performed in tissue microarray slides. IHC p53/p16 index was compared with the morphological classification.ConclusionsThe IHC p53/p16 index was a good marker for the differentiation of LGSOC and HGSOC, but the morphologic classification showed a better association with survival. FIGO stage and post-surgery residual disease remained the only independent prognostic factors for survival.

Second-harmonic generation microscopy represents an important tool to evaluate extracellular matrix collagen structure, which undergoes changes during cancer progression. Thus, it is potentially relevant to assess breast cancer development. We propose the use of second-harmonic generation images of tumor stroma selected on hematoxylin and eosin-stained slides to evaluate the prognostic value of collagen fibers analyses in peri and intratumoral areas in patients diagnosed with invasive ductal breast carcinoma. Quantitative analyses of collagen parameters were performed using ImageJ software. These parameters presented significantly higher values in peri than in intratumoral areas. Higher intratumoral collagen uniformity was associated with high pathological stages and with the presence of axillary lymph node metastasis. In patients with immunohistochemistry-based luminal subtype, higher intratumoral collagen uniformity and quantity were independently associated with poorer relapse-free and overall survival, respectively. A multivariate response recursive partitioning model determined 12.857 and 11.894 as the best cut-offs for intratumoral collagen quantity and uniformity, respectively. These values have shown high sensitivity and specificity to differentiate distinct outcomes. Values of intratumoral collagen quantity and uniformity exceeding the cut-offs were strongly associated with poorer relapse-free and overall survival. Our findings support a promising prognostic value of quantitative evaluation of intratumoral collagen by second-harmonic generation imaging mainly in the luminal subtype breast cancer.

Association between age at first sexual intercourse and subsequent human papillomavirus infection: results of a Brazilian screening program CeCília Maria roteli-Martins 1 adheMar longatto Filho 2 luCiano serpa haMMes 3 sophie Françoise MauriCette derChain 4 paulo naud 5 Jean Carlos de Matos 6 daniela etlinger 7 luis sarian 8 renata CleMentino gontiJo 9 Marina Yoshiê sakaMoto Maeda 10 kari Juhani sYrJänen 11 Artigos originais Resumo ObjetivO: descrever a idade de início da atividade sexual (sexarca) e a sua associação com a idade das mulheres com a infecção por papilomavírus humano (HPV) e com as alterações citológicas no exame de papanicolaou. MétOdOs: mulheres da população geral foram recrutadas para participar de um estudo de rastreamento de câncer cervical e lesões pré-malignas. Após a aplicação de questionário comportamental, foram submetidas ao rastreamento com gia cervical e teste para DNA de HPV de alto risco, por meio de Captura Híbrida 2. Este projeto faz parte do Latin American Screening Study, que envolve mulheres do Brasil e da Argentina, e os dados aqui apresentados referem-se aos centros brasileiros nas cidades de Porto Alegre, São Paulo e Campinas. ResultadOs: de 8.649 mulheres entrevistadas, 8.641 relataram atividade sexual prévia e foram incluídas na análise. A média de idade no momento da entrevista foi de 38,1±11,04 anos, com início da atividade sexual em média aos 18,5±4,0 anos. Identificamos que a idade do início da atividade sexual aumenta de acordo com o aumento da faixa etária no momento da entrevista, isto é, mulheres mais novas relataram sexarca mais precoce que mulheres mais velhas (p<0,001). Em relação à infecção por HPV de alto risco, do total de mulheres que haviam iniciado as relações sexuais, 3.463 foram testadas, com 17,3% de positividade para HPV. Notadamente, em todos os centros, as mulheres com idade ao início da atividade sexual abaixo da média da população entrevistada apresentaram positividade maior para HPV (20,2%) do que as mulheres com sexarca em idade acima da média (12,5%)-Odds Ratio (OR)=1,8 (IC95%=1,5-2,2; p<0,001). Em relação à citologia, mulheres com sexarca abaixo da média de idade apresentaram também maior percentual de citologia alterada ≥ ASC-US (6,7%) do que mulheres com sexarca em idade maior que a média (4,3%)-OR=1,6 (IC95%=1,3-2,0; p<0,001). COnClusões: a infecção por HPV e a presença de alterações citológicas identificadas no rastreio de lesões cervicais em uma população assintomática estiveram significativamente associadas à idade mais precoce no início das relações sexuais. Ademais, identificamos também que as mulheres desta amostra apresentaram diminuição da idade ao início da atividade sexual, nas últimas décadas, sugerindo importante causa para o acréscimo da prevalência de HPV e as lesões decorrentes desta infecção.

It is well known that persistent infection with high-risk HPV (hr-HPV), mostly HPV-16 and 18, is the main cause of cervical cancer development. Manganese superoxide dismutase (MnSOD or SOD2) are highly expressed in different neoplasia. The present study investigated SOD2 protein expression and the presence of hr-HPV types in 297 cervical samples including non-neoplastic tissue, cervical intraepithelial neoplasia grade 3 (CIN3), squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Strong SOD2 expression was significantly higher in ADC (82%) than CIN3 (52%) or SCC (64%). There was no association between SOD2 expression and HPV 16 and/or 18 detection for every lesion analyzed. Binary Logist Regression revealed that strong SOD2 expression (OR: 27.50, 6.16-122.81) and HPV 16 and/or HPV 18 (OR: 12.67, 4.04-39.74) were independently more associated with CIN3 than non-neoplastic cervix. Strong SOD2 expression (OR: 3.30, 1.23-8.86) and HPV 16 and/or HPV 18 (OR: 3.51, 1.03-11.87) were independently more associated with ADC than SCC. Similar findings for SOD2 expression were observed by the Cochran Mantel-Haenszel test, controlling for HPV-16 and/or HPV 18. In conclusion, the expression of SOD2 was increased in CIN3 and SCC, and more increased in cervical ADC than in SCC. Strong SOD2 expression was statistically independent of the presence of HPV 16 and/or 18. These findings suggest that the mitochondrial antioxidant system and HPV infection could follow independent pathways in the carcinogenesis of cervical epithelium and in the differentiation to SCC or ADC of the cervix.

Herein it was evaluated the impact of PD-L1 immunohistochemical expression and stromal tumor-infiltrating lymphocyte (sTIL) counts in pretreatment needle core biopsy on response to neoadjuvant chemotherapy (NACT) for patients with breast carcinomas (BC). In 127 paired pre- and post-NACT BC specimens, immunohistochemical expression of PD-L1 was evaluated in stroma and in neoplastic cells. In the same samples sTILs were semi-quantified in tumor stroma. Post-NACT specimens were histologically rated as having residual cancer burden (RCB of any degree), or with complete pathological response (pCR). PD-L1 expression and higher sTIL counts were associated with histological grade 3 BC. PD-L1 expression was also associated with the non-luminal-HER2+ and triple negative immunohistochemical profiles of BC. Pathological complete response was associated with histological grade 3 tumors, and with the non-luminal-HER2+ and triple negative profiles. Additionally, our results support an association between PD-L1 expression and pCR to NACT. It was also observed that there is a trend to reduction of sTIL counts in the post-NACT specimens of patients with pCR. Of note, PD-L1 was expressed in half of the hormone receptor positive cases, a finding that might expand the potential use of immune checkpoint inhibitors for BC patients.