No abstract

Purpose: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin.This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. Experimental Design: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. Results:Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. Conclusions: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished.Cancers of the uterus and ovary together account for 10% of new cancer cases and 7% of cancer deaths in women in the United States (1). Similarities in their histologic appearance have led to classification schemes that include serous, endometrioid, clear cell, and mucinous subtypes for both organs. However, the question of whether the presence of parallel subtypes in ovarian and endometrial cancer reflects common pathogenetic processes has not been clarified.The development of endometrial cancer is thought to involve two pathways. The classic or type I pathway occurs in the setting of estrogen excess, is associated with atypical hyperplasia as a precursor, and generally develops at an earlier age at a low stage and grade. In contrast, the alternative or type II pathway involves atrophic endometrium, proceeds through a precursor known as endometrial intraepithelial carcinoma, and presents in older patients and at a higher stage and grade (reviewed in ref.2). The first pathway is associated with endometrioid histopathology, whereas the second is linked to the serous subtype. Molecular evaluations have supported the distinction between the two types of endometrial cancer, showing that type I tumors tend to have frequent PTEN and ras mutations, be es...

CorrectionsMEDICAL SCIENCES. For the article ''Initiating oncogenic event determines gene-expression patterns of human breast cancer models,''