Kondi-Pafiti Agatha, Arkadopoulos Nikolaos, Gennatas Constantinos, Michalaki Vassiliki, Frangou-Plegmenou Matrona, Chatzipantelis Paschalis
Department of Pathology, Aretaieion Hospital, University of Athens Medical School, Athens, Greece.
Tumori. 2010 Nov-Dec;96(6):978-84.
c-kit (CD117) is a transmembrane tyrosine kinase that acts as a type III receptor for mast cell growth factor. In recent years, the role of c-kit in the development of preinvasive and invasive breast carcinomas has been investigated. The aim of our study was to detect c-kit expression in the entire spectrum of common benign and malignant breast lesions in correlation with a well-studied myoepithelial or stem-cell like marker (p63).
We evaluated 270 cases of benign and malignant breast lesions including fibrocystic disease, fibroadenoma, sclerosing adenosis, atypical ductal hyperplasia, ductal/lobular carcinoma in situ, and ductal/lobular/mixed type carcinoma. C-kit staining was evaluated in the cytoplasm/cell membrane in epithelial and myoepithelial cells and p63 in the nuclei of myoepithelial cells.
c-kit was highly expressed (85.3%) in benign lesions (fibrocystic disease, sclerosing adenosis, fibroadenoma), and p63 expression was 95.5% in the aforementioned lesions. c-kit distribution in preinvasive and invasive lesions was as follows: ductal/lobular carcinoma in-situ, 43%/35%; ductal/lobular carcinoma, 36%/39%; and mixed type carcinoma, 20%. c-kit was highly expressed in myofibroblast/fibroblast cells only in grade III ductal/lobular carcinomas. c-kit was totally absent in stromal cells in benign lesions and in situ carcinomas whereas expression was weak in grade I and II carcinomas.
Combined overexpression of c-kit and p63 is indicative of benign breast lesions. In contrast, there is reduced expression of c-kit in in situ and invasive breast carcinomas, with simultaneous overexpression in the stromal cells. This suggests that c-kit may play a role in breast cancer progression.
c-kit（CD117）是一种跨膜酪氨酸激酶，作为肥大细胞生长因子的III型受体发挥作用。近年来，已对c-kit在乳腺原位癌和浸润性癌发生发展中的作用进行了研究。我们研究的目的是检测常见的乳腺良恶性病变全谱中c-kit的表达情况，并与一种经过充分研究的肌上皮或干细胞样标志物（p63）进行相关性分析。
我们评估了270例乳腺良恶性病变，包括纤维囊性疾病、纤维腺瘤、硬化性腺病、非典型导管增生、导管/小叶原位癌以及导管/小叶/混合型癌。对上皮细胞和肌上皮细胞的细胞质/细胞膜中的c-kit染色以及肌上皮细胞核中的p63进行评估。
c-kit在良性病变（纤维囊性疾病、硬化性腺病、纤维腺瘤）中高表达（85.3%），上述病变中p63的表达为95.5%。c-kit在原位癌和浸润性病变中的分布如下：导管/小叶原位癌，43%/35%；导管/小叶癌，36%/39%；混合型癌，20%。仅在III级导管/小叶癌的肌成纤维细胞/成纤维细胞中c-kit高表达。c-kit在良性病变和原位癌的基质细胞中完全缺失，而在I级和II级癌中表达较弱。
c-kit和p63的联合过表达提示乳腺良性病变。相反，乳腺原位癌和浸润性癌中c-kit表达降低，而基质细胞中同时过表达。这表明c-kit可能在乳腺癌进展中发挥作用。
