Thyroid transcription factor-1 expression in normal gynecologic tissues and its potential significance

Thyroid transcription factor-1 (TTF-1) is a 38-kd nuclear protein, and a member of the NKx2 family of homeodomain transcription factors. It is highly expressed in normal and neoplastic thyroid and lung tissues, and is considered a reliable marker for lung adenocarcinoma and thyroid carcinoma. Recently, expression of TTF-1 has also been reported in ovarian, endometrial, and endocervical epithelial neoplasms. Little is known about TTF-1 immunoreactivity in normal gynecologic tissues. In this study, TTF-1 expression in various non-neoplastic gynecologic tissues was investigated by standard immunohistochemistry. One hundred and eight samples of benign gynecologic tissues from adult patients who had no known history of neoplastic condition were collected. Twenty-eight endometria (12 proliferative, 11 secretory, and 5 inactive), 26 fallopian tubes, 28 cervixes (14 endocervical and 14 ectocervical), 14 myometria, and 12 ovaries were studied. In addition, 4 normal fallopian tubes and 2 ovaries from 5 pediatric patients (aged from 3 mo to 11-yr old) were evaluated. Variable TTF-1 nuclear reactivity was identified in 25 of 26 (96%) fallopian tubes (extent of positivity ranged from 2% to 60%, median 25%), 15 of 28 (54%) endometria (1% to 10%, median 5%), and 6 of 14 (43%) endocervical samples (<5%). TTF-1 was also identified in 2 of 4 (50%) pediatric fallopian tubes with 5% and 20% of the tubal epithelium being positive, respectively. No TTF-1 expression was detected in ovarian tissue (neither epithelial nor stromal tissue; neither adult nor pediatric samples), ectocervical squamous epithelium or myometrium, nor in stromal tissue in endometrium, tube, or cervix. TTF-1 reactivity was detected in both proliferative and secretory endometrium, but not in 5 inactive endometria. TTF-1 is frequently expressed in normal/non-neoplastic tubal, and less frequently in functional endometrial and endocervical epithelia, but not in ovarian surface epithelium. TTF-1 might have a functional and developmental role in normal fallopian tube and endometrium, as it is highly expressed in tubal epithelium of both adults and young children, and in functional endometrium but not in inactive endometrium. The high TTF-1 expression in tubal epithelium but not in normal ovarian surface epithelium suggests that some TTF-1-positive ovarian tumors might be related to the tubal epithelium.