Increased expression of fatty acid synthase and progesterone receptor in early steps of human mammary carcinogenesis

International Journal of Cancer - Tập 120 Số 2 - Trang 224-229 - 2007
Majida Esslimani‐Sahla1,2, Simon Thézenas3, Thierry Chardès1, Andrew Kramar3, Roselyne Lavaill1, Dany Chalbos2, Henri Rochefort2
1Department of Pathology, Cancer Center Val d'Aurelle, Montpellier, France
2Endocrinologie Moléculaire et Cellulaire des Cancers (U540), Institut National de la Santé et de la Recherche Médicale (INSERM), 34090 Montpellier, France
3Department of Biostatistics, Cancer Center Val d'Aurelle, Montpellier, France

Tóm tắt

AbstractProgestins increase the risk of breast cancer in the hormone therapy of menopause, and progesterone receptor‐induced fatty acid synthase (FAS) is a potential therapeutical target of breast cancer. In a first attempt to specify in which lesions at risk of breast cancer progestins might be acting, we have compared the progesterone receptor (PR) and FAS expression in preinvasive breast lesions and in adjacent “normal” mammary glands. We used archive paraffin‐embedded tissues from 116 patients, with 164 lesions of increasing histological risk from nonproliferative “benign” breast disease (BBD) to in situ breast carcinomas. Immunostaining using our FAS antibody and a PR antibody from Dako was quantified as continuous variables by computer‐assisted image analysis. FAS level increased (p < 10−3 by the Kruskall–Wallis test) in all lesions, starting from nonproliferative BBD, and was maximal in in situ carcinoma. The % of PR‐positive cells increased from nonproliferative BBD and was higher in proliferative atypia (p < 10−3). It was very low in high‐grade DCIS corresponding to a likely different carcinogenesis pathway. There was a trend for a positive correlation between FAS and PR in normal glands. However, the 2 markers increased independently in BBD and were negatively correlated in in situ carcinomas. FAS and PR were positively correlated with Ki67 in BBD. The increased PR level in premalignant steps of mammary carcinogenesis suggests an early increased responsiveness to progestins. The increased FAS expression, in lesions parallel to their increased breast cancer risk, suggests further studies to develop new markers of high‐risk lesions and to prevent breast cancer. © 2006 Wiley‐Liss, Inc.

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Thông tin
Thông tin xuất bản

International Journal of Cancer

Tập 120 Số 2

224-229

Thông tin tác giả