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.
Highlights
Breast cancer (BC) is a serious public health issue, considering the number of women who are diagnosed and deaths that occur annually from this disease worldwide [1], and its clinical course and outcome vary from patient to patient depending on a complex series of factors [2,3,4,5,6].BC can be stratified though the expression of molecular markers, such as estrogen receptors (ER), progesterone receptors (RP), and human epidermal growth factor receptor 2 (HER2) overexpression or amplification, classifying the disease into four major molecular subtypes: Luminal A (LA; ER/PR + HER2-), Int
mammary tumor virus (MMTV)-like env gene was detected in 18.9% (41/217) of tumor tissues analyzed (Table 2)
26 were sequenced and compared to sequences deposited on the NCBI nucleotide bank through the BLAST algorithm, confirming the amplification of MMTV-like env gene
Summary
Breast cancer (BC) is a serious public health issue, considering the number of women who are diagnosed and deaths that occur annually from this disease worldwide [1], and its clinical course and outcome vary from patient to patient depending on a complex series of factors [2,3,4,5,6].BC can be stratified though the expression of molecular markers, such as estrogen receptors (ER), progesterone receptors (RP), and human epidermal growth factor receptor 2 (HER2) overexpression or amplification, classifying the disease into four major molecular subtypes: Luminal A (LA; ER/PR + HER2-), Int. Breast cancer (BC) is a serious public health issue, considering the number of women who are diagnosed and deaths that occur annually from this disease worldwide [1], and its clinical course and outcome vary from patient to patient depending on a complex series of factors [2,3,4,5,6]. Blood samples were tested for patients with MMTV-like env gene-positive tumors. Results: MMTV-like env sequence was detected in tumor and tumor-adjacent tissue samples from 41/217 and 30/196 patients, respectively. 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. 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
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