The role of four oestrogen-responsive genes, pLIV1, pS2, pSYD3 and pSYD8, in predicting responsiveness to endocrine therapy in primary breast cancer

Eur J Cancer. 1993;29A(10):1462-8. doi: 10.1016/0959-8049(93)90021-7.

Abstract

The expression of four oestrogen-responsive genes in 118 immunohistochemically defined primary breast tumours has been determined by northern analysis. While all the genes are induced by oestrogen in oestrogen receptor (ER)-positive cell lines, their behaviour is different in breast tumour biopsies. This behaviour can be divided into two groups; the first containing the genes, pLIV1 and pLIV2 (pS2), which both show a significant association with ER status (P = 0.001) and a corresponding inverse relationship with epidermal growth factor receptors (EGFR) (P = 0.01 and P = 0.08, respectively). In addition, the mRNA levels of both pLIV1 and pS2 are greater in ER-positive compared to ER-negative disease (P = 0.001). While a small number of ER-negative tumours were positive for either pLIV1 (12%) or pS2 (9%), we failed to observe co-expression of pLIV1 and pS2 in ER-negative disease. In ER-positive disease, four tumour populations were identified; ER+pLIV1-pS2-, ER+pLIV1-pS2+, ER+pLIV1+pS2- and ER+pLIV1+pS2+. Interestingly, the levels of pLIV1 and pS2 when co-expressed were significantly greater in ER+pLIV1+pS2+ tumours compared to either of the ER+pLIV1+pS2- (P = 0.03) or ER+pLIV1-pS2+ (P = 0.01) mixed phenotypes. Unlike pLIV1 and pS2, pSYD3 and pSYD8 belong to a group of genes which are expressed in the majority of tumours regardless of ER and EGFR status. However, lower pSYD8 mRNA levels were detected in moderately EGFR-positive disease (P = 0.06) while both pSYD3 positivity (P = 0.01) and mRNA levels (P = 0.001) were increased in highly proliferating tumours as shown by Ki67 immunostaining. These genes provide additional markers which, in conjunction with other parameters, may help to determine the likelihood of a given tumour to respond to endocrine therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Blotting, Northern
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • ErbB Receptors / analysis
  • Estrogens / therapeutic use*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ki-67 Antigen
  • Neoplasm Proteins / analysis
  • Nuclear Proteins / analysis
  • Oncogenes*
  • RNA, Neoplasm / analysis
  • Receptors, Estrogen / analysis

Substances

  • Biomarkers, Tumor
  • Estrogens
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Nuclear Proteins
  • RNA, Neoplasm
  • Receptors, Estrogen
  • ErbB Receptors