Absence of TTF-1 in Benign Endometrium and Simple Hyperplasia Is Associated with Progression to Cancer.
Peggy S Sullivan, Erin Maresh, Lee Goodglick, Madhuri Wadehra, Oliver Dorigo. UCLA David Geffen School of Medicine, Los Angeles, CA
Background: Thyroid transcription factor-1 (TTF-1) is thought to be specific for tissues of thyroid and lung origin. Its expression may be seen in Mullerian tissue; the significance of this is unknown. Recent studies show TTF-1 may inhibit the epithelial mesenchymal transition in lung adenocarcinomas (Saito, 2009) and that it may be a favorable prognostic factor in ovarian neoplasms (Fujiwara, 2010). We wanted to examine its role in early endometrioid carcinoma progression.
Design: Archived formalin fixed paraffin embedded endometrial tissues were obtained from 535 cases in 207 patients who either did or did not progress to carcinoma. Specimens were sampled mostly in triplicate as 1.1 mm cores for tissue microarray construction. Immunoperoxidase staining of TTF-1 antibody (Dako, Carpinteria, CA) was performed using a Dako autostainer. Scoring was performed by a single pathologist blinded to diagnosis and was recorded by intensity (0 to 3+) and percentage of glandular cells expressing TTF-1. A positive result was considered in any case with 1+, 1% or more cells with TTF-1 nuclear expression. Patients who developed non-endometrioid carcinoma, did not have a follow-up surgical case, and did not have informative TTF-1 information (e.g., no lesional epithelium for evaluation) were excluded from the analysis.
Results: 392 cases from 134 patients composed of benign endometrium (n=216), simple and complex hyperplasia (n=45), simple and complex atypical hyperplasia (n=25), and endometrioid carcinoma (n=106) were examined for TTF-1 nuclear expression. Significant differences of expression were noted in benign endometrium versus adenocarcinoma and non-atypical hyperplasia versus carcinoma (p=0.0007 and p=0.0530, respectively, Mann-Whitney U test). Absence of TTF-1 expression in benign endometrium and simple hyperplasia cases was associated with progression to cancer (p=0.00018, log-rank test). This association was not significant in hyperplasia alone, with or without atypia, although the numbers were small. TTF-1 was further shown to be an independent predictor of progression to cancer in multivariate analysis including cancer family history, diabetes, hypertension, body mass index, cancer diagnosis age, and age of menopause (p=0.0004, HR=0.089, 95% CI 0.023-0.339).
Conclusions: The absence of TTF-1 expression in benign endometrium and simple hyperplasia is an independent early predictor of endometrioid carcinoma suggesting that TTF-1 expression may play a protective role in benign and “early” endometrial lesions. The role of TTF-1 in advanced endometrial lesions remains to be elucidated.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 143, Wednesday Afternoon