A Large-Scale Gene Expression Comparison of Microdissected, Small-Sized Endometrial Cancers with or without Hyperplasia Matched to Same-Patient Normal Tissue

Purpose: Type I endometrial cancer is accompanied by hyperplasia and type II endometrial cancer is not. The purpose of our study is to identify genes involved in carcinogenesis of endometrial cancer, especially those differentially expressed by type I and type II cancers. Experimental Design: Using a cDNA array technique, we examined expression of 1176 cancer-related genes in endometrial cancer cells sampled from 21 tumors with a diameter of <10 mm, and we compared the expression patterns of the tumor cells with expression patterns of corresponding normal endometrial cells. Of these, 10 cases were type I cancers, and 11 cases were type II cancers. Laser capture microdissection directed precise separation of cells of interest from stromal cells. In cancer cells relative to normal cells, we identified genes that were commonly up- and down-regulated. Then we identified genes differentially expressed by the two types of cancer. Finally, in situ protein expression of some of these gene products was examined using immunohistochemistry. Results: Of 1176 genes examined, 32 genes were upregulated, and 58 were down-regulated in cancer cells (P < 0.05). Between the two types of cancer, 45 genes were highly expressed in type I cancers, and 24 were highly expressed in type II. Immunohistochemistry confirmed that P-cadherin expression was cancer specific, and vascular endothelial growth factor-C and MLH1 expression were limited to type I and type II cancers, respectively. Conclusions: A more accurate way of assessing gene expression during endometrial carcinogenesis shows evidence of providing candidate genes for use in conquering endometrial carcinoma.