Mouse Mammary Tumor Virus (MMTV)-Like env Sequence in Brazilian Breast Cancer Samples: Implications in Clinicopathological Parameters in Molecular Subtypes

Abstract

<b>Background:</b> Breast cancer (BC) is a complex disease in which susceptibility and clinical course depend on multiple factors. Evidence suggests that a mouse mammary tumor virus (MMTV)-homolog may be present in human BCs; however, little is known about its clinical implications. <b>Methods:</b> MMTV-like <i>env</i> nucleotide-sequence was searched in tumor and tumor-adjacent tissues from 217 Brazilian BC patients through nested-PCR and confirmed through PCR-sequencing. Blood samples were also tested for patients with MMTV-like <i>env</i> gene-positive tumors. Correlations with clinicopathological parameters were evaluated. <b>Results:</b> MMTV-like <i>env</i> sequence was detected in tumor and tumor-adjacent tissue samples from 41/217 and 30/196 patients, respectively. In blood, MMTV-like was detected in 17/32 patients. In Luminal-B tumors, MMTV-like in tumor tissue was negatively correlated with tumor size and disease stage, whereas in HER2 tumors it anti-correlated with lymph node metastasis (LNM) and disease stage. Considering blood, MMTV-like <i>env</i> gene positivity negatively correlated with age in general BC, while in Luminal-A tumors it positively correlated with Ki67 but negatively correlated with age and LNM. The associations with decreased LNM frequency were independent of other prognostic factors. <b>Conclusion:</b> MMTV-like <i>env</i> positivity is associated with better prognostic parameters in BC subtypes, which might be explainable by its anti-metastatic potential and by putative activation of immune milieu.