[1192] Multiple Molecular Pathways in the Development of Uterine Serous Carcinoma

AD Tabrizi, CB Gilks. Tabriz University of Medical Science, Tabriz, East Azarbyjan, Islamic Republic of Iran; University of British Columbia, Vancouver, BC, Canada

Background: A pathway for development of frankly invasive uterine serous carcinoma through endometrial glandular dysplasia (EmGD) to intraepithelial and invasive serous carcinoma has been proposed.
Design: We present histologic and immunohistochemical findings in 26 cases of endometrial serous carcinoma and their putative precursor lesions, based on a study of cases of serous carcinoma of the endometrium involving endometrial polyps. Immunostaining for six markers (p53, PTEN, Ki67, p16, ER, and PR) were performed in selected sections of these cases.
Results: In five cases EmGD, characterised by glands lined by atypical cells but not showing a sufficient degree of cytological atypia or mitotic activity to warrant a diagnosis of endometrial intraepithelial carcinoma (EIC), was present adjacent to the EIC and invasive serous carcinoma, and in these cases all three components showed identical immunostaining patterns for, PTEN, p16, ER and PR for a given case, and the results for P53 and Ki 67 showed increasing score from EmGD to EIC. In four cases, hyperplastic glands showing crowded architecture, and lined by cells with low grade atypia, similar to that seen in atypical hyperplasia of the endometrium, were present adjacent to the serous carcinoma. These cases showed ER positivity and PTEN negativity in the hyperplasitic areas, with at least focal p53 positivity. In the remaining 17 cases no EmGD or atypical hyperplastic lesions were identified. As a control group we examined 8 cases of atypical endometrial hyperplasia with no associated carcinoma. All 8 these cases were negative for P53 and positive for ER, PR and showed at least one focus of PTEN null glands.
Conclusions: This study suggests that there are different molecular pathways leading to development of uterine serous carcinoma, i.e. through EmGD, with p53 mutation in nonhyperplastic glands, in cells that lack expression of hormone receptors and do not have loss of PTEN expression, or through atypical hyperplasia of the endometrium, with p53 mutation occurring in cells that express hormone receptors and show loss of PTEN expression.
Category: Gynecologic & Obstetrics

Monday, March 22, 2010 2:15 PM

Platform Session: Section C, Monday Afternoon

 

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