TTF1 Expression Is Increased with Progression to Endometrioid Carcinoma: A Tissue Microarray Analysis
RH Finck, O Dorigo, SM Dry, M Wadehra, J Braun, D Seligson, PS Sullivan. University of California, Los Angeles, Los Angeles, CA
Background: Thyroid transcription factor-1 (TTF-1) is a transcription factor expressed in lung and thyroid tissues. Its expression by a tumor is often considered a reliable marker of origination from these tissues. However, its expression has been reported in various uterine neoplasms ranging from 22% in endometrioid carcinomas to 82% in carcinosarcomas (Zhang et al, 2009), suggesting its role as a marker of aberrancy with less differentiated neoplasms. We sought to determine the expression of TTF-1 in an “early” progression array of normal endometrium, hyperplasia, and endometrioid endometrial carcinoma.
Design: A tissue microarray was constructed from formalin-fixed paraffin-embedded endometrial specimens, composed of 119 endometrioid carcinomas (EC), 87 complex atypical hyperplasia (CAH), 50 complex hyperplasia (CH), 27 simple atypical hyperplasia (SAH), 138 simple hyperplasia (SH), and 336 normal endometrial controls. Specimens were sampled mostly in triplicate as 1.1 mm cores. 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 (a scale of 0-3) and percentage of endometrial glandular cells expressing TTF-1. A positive result was considered for cases with at least 1+ nuclear staining in 10% of cells.
Results: 132 (17.4%) of a total of 757 samples were considered positive. TTF-1 expression was generally nuclear and 1+ in intensity with several cases staining 2+ or more. The percentage of cases expressing TTF-1 was as follows: normal 11.3%, SH 10.8%, SAH 18.5%, CH 26%, CAH 26.4%, and carcinoma 31.9%. Statistically significant differences were found in TTF-1 expression between normal and SH to CH (p=0.004), CAH (p=0.0003), and EC (p<0.0001, all Chi-squared tests).
Conclusions: TTF-1 nuclear expression is seen in benign endometrium, hyperplasia, and endometrioid carcinoma. Its expression appears to increase with complex hyperplasia with and without atypia, and carcinoma, suggesting it may be associated with progression to hyperplasia and carcinoma. Nuclear expression is seen in up to 31.9% of endometrioid carcinomas (as supported by previous studies, Zhang 2009, Siami 2007, Alkushi 2003). This finding is significant as it may render the evaluation of possible metastatic lesions difficult, particularly in the case of a lung mass in a patient with a history of endometrioid adenocarcinoma.
Category: Gynecologic & Obstetrics
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 153, Monday Morning