BackgroundGastric cancer is usually diagnosed in an advanced stage of disease and treatment options are sparse. Trastuzumab was recently approved for metastatic or locally advanced carcinomas arising in the stomach or in the gastroesophageal junction in patients with HER2-positive tumors. However, data on the frequency of HER2-positive cases among Brazilian patients are limited. Our aim was to characterize HER2 protein and gene status in a series of Brazilian patients with gastric cancer and to evaluate its association with clinicopathological data.MethodsHistological slides from 124 primary gastrectomies were reviewed and their pathological reports were retrieved from the files at a Brazilian university hospital. Automated immunohistochemistry for HER2 was performed on whole-tissue sections from each tumor. HER2-equivocal cases by immunohistochemistry were submitted to automated dual in situ hybridization for gene amplification evaluation. HER2 status was confronted with clinicopathological parameters in order to assess statistically significant associations.ResultsImmunohistochemistry analysis revealed that 13/124 cases (10.5 %) were HER2 positive (3+), 10/124 cases (8.1 %) were equivocal (2+) and 101/124 cases (81.4 %) were negative, being 7 cases 1+. None of the equivocal cases showed gene amplification. The overall HER2 positivity rate was 10.5 %. There was an association between HER2 expression and Laurén’s intestinal histological subtype (P = 0.048), well to moderately differentiated tumors (P = 0.004) and presence of lymphovascular invasion (P = 0.031). No association was found between HER2 status and tumor topography.ConclusionsConfronted with data published by other authors, the lower percentage of HER2-positive cases found in our series might be partially explained by the lower frequency of tumors arising at the gastroesophageal junction in comparison with distal gastric carcinomas in Brazilian patients. This could also account for the lack of statistically significant association between HER2 status and tumor topography in our study.

Bovine leukemia virus (BLV) is a retrovirus that causes lymphoma in cattle worldwide and has also been associated with breast cancer in humans. The mechanism of BLV infection in humans and its implication as a primary cause of cancer in women are not known yet. BLV infection in humans may be caused by the consumption of milk and milk-products or meat from infected animals. Breast cancer incidence rates in Brazil are high, corresponding to 29.5% a year of cancer cases among women. In 2020, an estimated 66,280 new cases of breast cancer are expected, whereas in 2018 breast cancer has led to 17,572 deaths, the highest incidence and lethality among cancers in women in this country that year. BLV infection occurrence ranges from 60 to 95% in dairy herds. In addition, there are some regions, such as the Minas Gerais State, southeastern Brazil, where the population traditionally consume unpasteurized dairy products. Taken together, this study aimed to verify if there is a higher association between breast cancer and the presence of BLV genome in breast tissue samples within this population that consumes raw milk from animals with high rates of BLV infection. A molecular study of two BLV genes was carried out in 88 breast parenchyma samples, between tumors and controls. The amplified fragment was subjected to BLV proviral sequencing and its identity was confirmed using GenBank. BLV proviral genes were amplified from tumor breast parenchyma samples and healthy tissue control samples from women, revealing a 95.9% (47/49) and 59% (23/39) positivity, respectively. Our results show the highest correlation of BLV and human breast cancer found in the world to date within the population of Minas Gerais, Brazil.

Follistatin is a potent native activin antagonist that is expressed in the normal mammary gland and in different breast proliferative diseases. Despite experimental evidence that follistatin can modulate the breast cancer cell cycle, the clinical significance of follistatin expression in these tumors is unknown. The aim of this study was to correlate the intensity of follistatin expression in invasive breast cancer with some of its clinical and pathologic features, such as the disease stage and the hormonal receptor status. Paraffin blocks of tumor samples that had been fixed in buffered formalin were obtained from 154 women subjected to surgery for breast cancer between 2008 and 2012. Sections from all paraffin blocks were cut and processed together by immunohistochemistry using a commercial monoclonal antibody to human follistatin. The intensity of follistatin staining was unrelated to the menopausal status, the disease stage, the grade, progesterone receptor expression, and local or systemic recurrence. However, follistatin immunoreactivity was significantly stronger in estrogen receptor (ER)-negative tumors than in ER-positive tumors. These findings suggest that follistatin expression in invasive breast cancer is unrelated to the disease severity and the risk of recurrence, but is more intense in ER-negative tumors.

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There was very good agreement among the five anti-HER2 antibodies. CB11 was the most specific antibody, but showed more false negative cases. A0485, SP3, 4B5 and HercepTest were highly sensitive and specific, but showed more false positive cases.