Bovine leukemia virus presence in breast tissue of Argentinian women. Its association with cell proliferation and prognosis markers.

Abstract

Introduction: Bovine leukemia virus (BLV) causes enzootic bovine leukemia, and is closely related to human T-lymphotropic virus type 1. It expresses microRNAs of unknown function and codes Tax, the protein that mediates malignant transformation. BLV is capable of infecting Band T-lymphocytes, endothelial cells, and mammary epithelial cells of cattle. Several studies demonstrated the presence of BLV DNA in human tissue, and it is significantly associated with breast cancer in case-control studies using in situ Polymerase Chain Reaction (PCR), a highly sensitive and specific technique. The current study was the first report of BLV DNA detection by in situ PCR in tissue from Argentinian females with a diagnosis of breast cancer. Methods: In situ PCR was done to detect BLV DNA in 85 human FFPE breast cancer tissue samples. The association of BLV DNA and expression of Ki67 and Her-2 was assessed. Results: BLV DNA presence could be determined in 22.6% of the analyzed samples, and its presence was associated with an increase of the expression and prognostic markers Ki67 (P=0.009) and HER-2 (P=0.044) determined by conventional immunohistochemistry. No statistical significance was observed between the presence or absence of hormonal receptors and the presence of BLV DNA. Conclusions: The obtained results support the idea that BLV might play a role in malignant tissue transformation.

High positivity values for bovine leukemia virus in human breast cancer cases from Minas Gerais, Brazil

“…In humans BLV has been associated with breast cancer, but the results are still contradictory. Some authors have failed to find evidence of this relationship [10,13], while others claim that such an association exists [5][6][7][8][9]. Our results show a high occurrence of the BLV (provirus) genome in tumor mammary parenchyma samples: 95.9% (47/49), against 59% (23/39) in healthy control tissues, demonstrating a high association of BLV with human breast cancer in the studied population, corroborating most of the results published.…”

“…However, the small number of tumor tissues negative for BLV (n = 2) did not generate good statistical support for this type of analysis. Other studies that analyzed this correlation did not find significant values [7,9]. This suggests that BLV is not related to the prognosis of the disease and consequent patient survival.…”

“…Some viruses have been found in the human breast parenchyma such as Mouse mammary tumor virus (MMTV), Epstein-Barr virus (EBV), and Human papillomavirus (HPV) in both healthy and cancerous samples [4]. Recently, some reports have associated Bovine leukemia virus (BLV) with breast cancer in humans due to a higher prevalence of BLV-provirus in cancerous tissues compared to healthy ones [5][6][7][8][9]. In the USA, 59% of breast tumor tissues have been BLV positive versus 29% for control tissues [5].…”

Bovine leukemia virus relation to human breast cancer: Meta-analysis

“…In some of the studies, there is a clear upward gradient of bovine leukemia virus presence from control to cancerous patients. STUDY Breast Cancer Will Develop Control Country Buehring 2015 [ 15 ] 59% 38% 29% USA Schwingel 2019 [ 20 ] 30.5% 13.9% Brazil Ceriani 2018 [ 24 ] 22.6% Argentina Buehring 2017 [ 22 ] 80% 74.2% 41% Australia Giovanna 2013 [ 26 ] 35.8% 45% Colombia …”

“…According to Ceriani et al, BLV was present in 22.6% of 85 Argentinian breast cancer samples using PCR and the presence of BLV was associated with increases in the cancer biomarkers Ki67 and Her-2 [ 24 ]. They report that their results support that BLV could play a role in malignant tissue creation.…”