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

Abstract

Background: 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. Methods: MMTV-like env 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 env gene-positive tumors. Correlations with clinicopathological parameters were evaluated. Results: MMTV-like env 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 env 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. Conclusion: MMTV-like env 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.

Mouse Mammary Tumor Virus (MMTV) and MMTV-like Viruses: An In-depth Look at a Controversial Issue

“…BC discovered during pregnancy or lactation is known to be very aggressive and of poor prognosis, probably because of the effect of hormones on the stimulation of cellular growth [ 143 , 144 ]. However, in contrast with the previous reports, although triple-negative BC (TNBC) is considered one of the most aggressive ones among the molecular subtypes of BC [ 145 , 146 ], Gupta et al [ 147 ] unexpectedly found that MMTVels were present in only 7% of TNBC samples from a Croatian cohort, and similar findings (4%) came from a Brazilian TNBC cohort [ 148 ].…”

Presence of high-risk HPVs, EBV, and MMTV in human triple-negative breast cancer

“…In the present study, we found that the MMTV-like virus gene is present in only 7% of TNBC samples from the Croatian cohort, similar to findings from a Brazilian TNBC cohort (4%). 98 Moreover, MMTV-like virus was detected in 19%, 17%, and 14% of breast cancer samples in Brazilian, 98 Chinese, 101 and Tunisian 100 populations. Another study by Liu et al 108 isolated a complete provirus from human breast cancer samples, while a study by Lawson et al 45 detected MMTV-like antigens and sequences in benign lesions that developed to breast cancer in women during later years.…”

“…However, similar to other studies, in this study, we did not find any association between the presence/co-presence of HPVs, EBV, and MMTV-like virus and clinicopathological characteristics. 94 , 116 However, de Sousa Pereira et al found a correlation between MMTV-like virus and clinicopathological features in Luminal B and HER2-positive samples, 98 thus indicating that MMTV-like presence may display subtype-specific effects in breast cancer. Thus, further studies are needed to evaluate the role of the MMTV-like virus in a larger breast cancer cohort.…”

MMTV Prevalence in Breast Cancer Samples in Romania- Do Major Geographical Differences Exist in the World Population?

“…MMTV-related breast cancers tend to be less aggressive as well. [36] Other virus infections have been proposed as well as causative agents of breast cancer, the most studied being bovine leukemia virus (BLV). [37] Breast cancer remains one of the most mysterious human cancers, since most cases cannot be linked to specific risk factors.…”