Evaluation of E6 and E7 mRNA expression in HPV DNA positive breast cancer

Several studies have suggested a possible role for HPV in the pathogenesis of the breast cancer. We investigated the presence of the HPV DNA in breast cancers and non malignant disease breast tissues by the use of a standard HPV detection method (INNO-Lipa HPV), in order to detect HPV DNA in metastatic nodes, to investigate a possible cervical HPV co-infection, and to evaluate the E6/E7 mRNA expression in HPV DNA positive breast cancer tissues. The rate of HPV infection was significantly higher in the cancer group than in controls (9/31 vs 0/12, p = 0.04). One out of eight metastatic axillary nodes was positive for HPV infection; 2/3 of the positive HPV breast cancer patients were co-infected at the cervical site. The role of the virus in breast oncogenesis is still unclear, since our analysis failed in demonstrating the expression of viral E6 and E7 in positive HPV positive breast tumor tissues.

Breast cancer; E6; E7; HPV; HPV 16

[1] AIRTUM; I tumori in Italia: Rapporto 2006. www.registritumori. it/incidenza1998 -2002/gruppi.html.

[2] Zhi-Ming Z., Backer C.C.: “Papillomavirus genome structure, expression, and post-transcriptional regulation”. Front. Biosci., 2006, 11, 2286.

[3] Stanley M.: “Prophylactic HPV vaccines: prospects for eliminating ano-genital cancer”. Br. J. Cancer, 2007, 96, 1320.

[4] de Villiers E.M., Sandstrom R.E., zur Hausen H., Buck C.E.:“Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast”. Breast Cancer Res., 2005, 7, R1.

[5] Mendizabal-Ruiz A.P., Morales J.A., Ramirez-Jirano L.J., Padilla-Rosas M., Morán-Moguel M.C., Montoya-Fuentes H.: “Low frequency of human papillomavirus DNA in breast cancer tissue”. Breast Cancer Res. Treat., 2009, 114, 189.

[6] Di Leonardo A., Venuti A., Marcante M.L.: “Human papilloma virus in breast cancer”. Breast Cancer Res. Treat., 1992, 21, 95.

[7] Wrede D., Luqmani Y.A., Coombes R.C., Vousden K.H.: “Absence of HPV 16 and 18 DNA in breast cancer”. Br. J. Cancer, 1992, 65, 891.

[8] Gopalkrishna V., Singh U.R., Sodhani P., Sharma J.K., Hedau S.T., Mandal A.K., Das B.C.: “Absence of human papillomavirus DNA in breast cancer as revealed by polymerase chain reaction”. Breast Cancer Res. Treat., 1996, 39, 197.

[9] Yu Y., Morimoto T., Sasa M., Okazaki K., Harada Y., Fujiwara T., Irie Y., Takahashi E., Tanigami A., Izumi K.: “HPV 33 DNA in premalignant and malignant breast lesions in Chinese and Japanase population”. Anticancer Res., 1999, 19, 5057.

[10] Liu Y., Klimberg V.S., Andrews N.R., Hicks C.R., Peng H., Chiriva-Internati M. et al.: “Human papillomavirus DNA is present in a subset of unselected breast cancers”. J. Hum. Virol., 2001, 4, 329.

[11] Li T., Lu Z.M., Guo M., Wu Q.J., Chen K.N., Xing H.P. et al.: “p53 codon 72 polymorphism (C/G) and the risk of human papillomavirus-associated carcinomas in China”. Cancer, 2002, 95, 2571.

[12] Damin A.P., Karam R., Zettler C.G., Caleffi M., Alexandre C.O.: “Evidence for an association of human papillomavirus and breast carcinomas”. Breast Cancer Res. Treat., 2004, 84, 131.

[13] Widschwendter A., Brunhuber T., Wiedemair A., Mueller-Holzner E., Marth C.: “Detection of human papillomavirus DNA in breast cancer of patients with cervical cancer history”. J. Clin. Virol., 2004, 31, 292.

[14] Kan C.Y., Iacopetta B.J., Lawson J.S., Whitaker N.: “Identification of human papillomavirus DNA gene sequences in human breast cancer”. Br. J. Cancer, 2005, 93, 946.

[15] Tsai J.H., Tsai C.H., Cheng M.H., Lin S.J., Xu F.L., Yang C.C.: “Association of viral factors with non-familial breast cancer in Taiwan by comparison with non-cancerous, fibroadenoma, and thyroid tumor tissues”. J. Med. Virol., 2005, 75, 276,

[16] Gumus M., Yumuk P.F., Salepci T., Aliustaoglu M., Dane F., Ekenel M. et al.: “HPV DNA frequency and subset analysis in human breast cancer patients’ normal and tumoral tissue samples”. J. Exp. Clin. Cancer Res., 2006, 25, 515.

[17] Kroupis C., Markou A., Vourlidis N., Dionyssiou-Asteriou A., Lianidou E.S.: “Presence of high-risk human papillomavirus sequences in breast cancer tissues and association with histopathological characteristics”. Clin. Biochem., 2006, 39, 727.

[18] Lindel K., Forster A., Altermatt H.J., Greiner R., Gruber G.: “Breast cancer and human papillomavirus (HPV) infection: no evidence of a viral etiology in a group of Swiss women”. Breast (Edinburgh, Scotland), 2007, 16, 172.

[19] Yavuzer D., Salepci T., Karadayi N., Baloglu H., Kucukodaci Z.: “Human papillomavirus is not associated with breast carcinoma”. Breast Cancer Res. Treat., 2010, 122, 899.

[20] Khan N.A., Castillo A., Koriyama C., Kijima Y., Umekita Y., Ohi Y. et al.: “Human papillomavirus detected in female breast carcinomas in Japan”. Br. J. Cancer, 2008, 99, 408.

[21] Pett M., Coleman N.: “Integration of high-risk human papillomavirus: a key event in cervical carcinogenesis?”. J. Pathol., 2007, 212, 356.