title: Expression of Human Endogenous Retrovirus Type K Envelope Protein is a Novel Candidate Prognostic Marker for Human Breast Cancer.
abstract: We previously observed that the HERV type K (HERV-K) envelope (env) protein was expressed in the majority of human breast tumors from a U.S. cohort of women from Texas. We also made the preliminary observation that the expression of HERV-K env transcripts was associated with markers of disease progression. In this follow-up study, env protein expression was evaluated immunohistochemically in an additional 195 paraffin-embedded breast tumors from a second U.S. patient cohort (Baltimore, Maryland) and in 110 tumors from Chinese patients. Moreover, we compared env transcript expression between fresh-frozen normal and cancerous breast tissues. We observed that while env mRNA and protein expression was undetectable in normal breast tissue and in a subset of uninvolved normal-appearing tissue adjacent to the tumor epithelium, it was overexpressed in most tumors. Furthermore, env expression was associated with breast cancer progression. In Baltimore cohort women, HERV-K tumor positivity was significantly associated with disease stage and lymph node metastasis. In Chinese women, HERV-K env positivity was significantly associated with tumor size, TNM stage, and lymph node metastases, which is consistent with the observations in the U.S. cohort. We also found that Chinese breast cancer patients with a high expression of HERV-K had a decreased overall survival compared with patients who had either a moderate or low HERV-K expression in their tumors (P = 0.049, χ(2) log rank test). In conclusion, the HERV-K env gene is expressed in the majority of breast cancers from U.S. or Chinese women but not in normal breast tissue. High expression of HERV-K env protein in breast cancer patients is associated with markers of disease progression and poor disease outcome, indicating that HERV-K env protein is a novel candidate prognostic marker for breast cancer.
authors.affiliation: Cancer Institute and Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Kiera
authors.initials: K
authors.lastname: Rycaj
authors.forename: Shanshan
authors.initials: S
authors.lastname: Geng
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Plummer
authors.forename: Bingnan
authors.initials: B
authors.lastname: Yin
authors.forename: Hong
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authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Xu
authors.forename: Yinchun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Yan
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Glynn
authors.forename: Tiffany H
authors.initials: TH
authors.lastname: Dorsey
authors.forename: Stefan
authors.initials: S
authors.lastname: Ambs
authors.forename: Gary L
authors.initials: GL
authors.lastname: Johanning
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.forename: Feng
authors.initials: F
authors.lastname: Wang-Johanning