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

Manning, D. L., McClelland, Richard Andrew, Gee, Julia Margaret Wendy, Chan, C. M. W., Green, C. D., Blamey, R. M. and Nicholson, Robert Ian 1993. The role of four oestrogen-responsive genes, pLIV1, pS2, pSYD3 and pSYD8, in predicting responsiveness to endocrine therapy in primary breast cancer. European Journal of Cancer 29 (10) , pp. 1462-1468. 10.1016/0959-8049(93)90021-7

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Publisher: Elsevier
ISSN: 0014-2964
Last Modified: 12 Jun 2019 02:09
URI: http://orca-mwe.cf.ac.uk/id/eprint/17130

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