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.