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 ORCID: https://orcid.org/0000-0001-6483-2015, 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:	18 Oct 2022 14:19
URI:	https://orca.cardiff.ac.uk/id/eprint/17130

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