PMID- 29868468 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220317 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 8 DP - 2018 TI - Association of Mouse Mammary Tumor Virus With Human Breast Cancer: Histology, Immunohistochemistry and Polymerase Chain Reaction Analyses. PG - 141 LID - 10.3389/fonc.2018.00141 [doi] LID - 141 AB - PURPOSE: The purpose of this study is to determine whether mouse mammary tumor virus (MMTV)-associated human breast cancer has the same or similar histology to MMTV-associated mouse mammary tumors. Such associations may indicate a role for MMTV in human breast cancer. METHODS: Immunohistochemical techniques (using antibodies directed against the signal peptide p14 of the envelope precursor protein of MMTV) and polymerase chain reaction (PCR) analyses were used to identify MMTV proteins and MMTV-like envelope gene sequences in a series of breast cancers from Australian women. The histological characteristics of these human breast cancer specimens were compared with MMTV positive mouse mammary tumors. The same methods were used to study benign breast tissues which 1-11 years later developed into breast cancer. RESULTS: MMTV p14 proteins were identified in 27 (54%) of 50 human breast cancers. MMTV env gene sequences were identified by PCR in 12 (27%) of 45 human breast cancers. There was a significant correlation between the presence of MMTV (identified by p14 immunohistochemistry) in human breast cancers and histological characteristics similar to MMTV positive mouse mammary tumors (p = 0.001). There was a non-significant correlation between the presence of MMTV env gene sequences (identified by PCR) in human breast cancers and histological characteristics similar to MMTV positive mouse mammary tumors (p = 0.290). MMTV p14 proteins were identified in 7 (54%) of 13 benign breast specimens that later developed into human breast cancers. MMTV by PCR was identified in two benign specimens one of whom later developed MMTV positive breast cancer. DISCUSSION: These observations offer evidence that MMTV may be associated with characteristic human breast cancer histology. p14-based immunohistochemistry appears to be a more reliable technique than PCR for the identification of MMTV in human breast cancer. Identification of MMTV-associated p14 proteins in benign breast tissues confirms prior PCR-based studies that MMTV infection occurs before the development of MMTV positive breast cancer. CONCLUSION: Many MMTV positive human breast cancers have similar histology to MMTV positive mouse mammary tumors. MMTV infection identified in benign breast tissues precedes development of MMTV positive human breast cancer. When considered in the context of prior studies, these observations indicate a likely role for MMTV in human breast cancer. FAU - Lawson, James S AU - Lawson JS AD - University of New South Wales, Sydney, NSW, Australia. FAU - Mazzanti, Chiara AU - Mazzanti C AD - Fondazione Pisana per la Scienza Onlus, Pisa, Italy. FAU - Civita, Prospero AU - Civita P AD - Fondazione Pisana per la Scienza Onlus, Pisa, Italy. FAU - Menicagli, Michele AU - Menicagli M AD - Fondazione Pisana per la Scienza Onlus, Pisa, Italy. FAU - Ngan, Christopher C AU - Ngan CC AD - University of New South Wales, Sydney, NSW, Australia. FAU - Whitaker, Noel J AU - Whitaker NJ AD - University of New South Wales, Sydney, NSW, Australia. FAU - Hochman, Jacob AU - Hochman J AD - Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Braitbard, Ori AU - Braitbard O AD - Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Yosufi, Benafsha AU - Yosufi B AD - Douglass Hanly Moir Pathology, Macquarie Park, NSW, Australia. FAU - Glenn, Wendy K AU - Glenn WK AD - University of New South Wales, Sydney, NSW, Australia. LA - eng PT - Journal Article DEP - 20180507 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC5950654 OTO - NOTNLM OT - breast cancer OT - histology OT - immunohistochemistry OT - mouse mammary tumor virus OT - mouse mammary tumor virus p14 OT - mouse mammary tumor virus signal peptide OT - mouse mammary tumors OT - polymerase chain reaction EDAT- 2018/06/06 06:00 MHDA- 2018/06/06 06:01 PMCR- 2018/01/01 CRDT- 2018/06/06 06:00 PHST- 2018/01/30 00:00 [received] PHST- 2018/04/18 00:00 [accepted] PHST- 2018/06/06 06:00 [entrez] PHST- 2018/06/06 06:00 [pubmed] PHST- 2018/06/06 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2018.00141 [doi] PST - epublish SO - Front Oncol. 2018 May 7;8:141. doi: 10.3389/fonc.2018.00141. eCollection 2018.