Significance of c-kit Expression in Breast Ductal Carcinoma
D Bautista, ML Bernal, A Jimenez, I Arranz, S Luna. Hospital Carlos Haya, Malaga, Spain; DG Innovacion Sanitaria, Sistemas y Tecnologias, Sevilla, Spain
Background: The c-kit gene encodes a transmembrane tyrosine kinase growth factor receptor (CD117) involved in certain neoplasms. Conflicting results concerning c-kit expression have been reported in malignant breast lesions. Using immunohistochemical approaches, c-kit expression is lost in most breast neoplasms. However, an increase of c-kit expression has been associated with aggressiveness and poor outcome. Flt3 (CD135), a tyrosine kinase receptor expressed in normal breast epithelial cells, has been found to interact with c-kit by heterodimerization. This study has tried to characterize c-kit expression changes within the spectrum of breast ductal carcinoma.
Design: One hundred and twenty eight cases of invasive ductal carcinoma were selected from our local Tumor Bank. Expression of c-kit gene was analyzed by quantitative real-time PCR using cytokeratin 18 as expression reference for breast epithelial cells in both, normal and tumor samples. In parallel, c-kit protein expression was evaluated by immunohistochemistry using the polyclonal rabbit anti-human CD117 antibody from Dako and the Bond Polymer Refine Detection from Leica Microsystems. The same method was used to analyze Flt3 protein expression in normal and tumor breast samples using a polyclonal rabbit anti-human antibody from Abcam.
Results: c-kit was expressed at both mRNA and protein levels in normal breast epithelial cells. However, the analysis of tumor regions with different methodologies gave somewhat discordant results. Protein expression was lost in most invasive breast cancers (89,84%) and only maintained in a subset of tumors with high proliferative activity at advance stage (>2cm). mRNA expression was maintained at normal levels in many neoplasms (51,72%) and no relation was found with protein expression. Surprisingly, a decrease of gene expression was statistically associated with large tumor size. We found Flt3 to be expressed in most in situ and infiltrative breast cancers, and no related with c-kit status.
Conclusions: c-kit plays an important role in the maintenance of normal mammary epithelium and neoplastic transformation leads to its lost. The significance of c-kit protein expression in a minority of advanced, highly proliferative breast ductal carcinomas keeps still unexplained since no relation with gene activation or interaction with Flt3 have been found.
Monday, March 9, 2009 1:00 PM
Poster Session II # 52, Monday Afternoon