Esslimani-Sahla Majida, Thezenas Simon, Simony-Lafontaine Joelle, Kramar Andrew, Lavaill Roselyne, Chalbos Dany, Rochefort Henri
Endocrinologie Moléculaire et Cellulaire des Cancers (U540), Institut National de la Santé et de la Recherche Médicale (INSERM), 34090 Montpellier, France.
Int J Cancer. 2007 Jan 15;120(2):224-9. doi: 10.1002/ijc.22202.
Progestins 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.
在更年期激素治疗中，孕激素会增加患乳腺癌的风险，而孕激素受体诱导的脂肪酸合酶（FAS）是乳腺癌潜在的治疗靶点。为了初步确定孕激素可能作用于哪些有乳腺癌风险的病变，我们比较了乳腺浸润前病变和相邻“正常”乳腺组织中孕激素受体（PR）和FAS的表达。我们使用了116例患者的存档石蜡包埋组织，其中有164个病变，其组织学风险从非增殖性“良性”乳腺疾病（BBD）到原位乳腺癌逐渐增加。使用我们的FAS抗体和Dako公司的PR抗体进行免疫染色，通过计算机辅助图像分析将其量化为连续变量。FAS水平在所有病变中均升高（通过Kruskal-Wallis检验，p<10⁻³），从非增殖性BBD开始，在原位癌中最高。PR阳性细胞的百分比从非增殖性BBD开始增加，在增殖性异型增生中更高（p<10⁻³）。在对应于可能不同致癌途径的高级别导管原位癌中其水平非常低。在正常腺体中，FAS和PR之间有正相关的趋势。然而，在BBD中这两种标志物独立增加，而在原位癌中呈负相关。在BBD中，FAS和PR与Ki67呈正相关。乳腺致癌前阶段PR水平的升高表明对孕激素的反应性早期增加。FAS表达在与乳腺癌风险增加平行的病变中升高，这提示需要进一步研究以开发高危病变的新标志物并预防乳腺癌。
