Thyroid Transcription Factor-1 Expression Correlates with Predominant Histologic Subtypes and Recurrence in Stage I Lung Adenocarcinoma Patients
Kyuichi Kadota, Jun-Ichi Nitadori, Kei Suzuki, Camelia S Sima, Akihiko Yoshizawa, Valerie W Rusch, William D Travis, Prasad S Adusumilli. Memorial Sloan-Kettering Cancer Center, New York
Background: The majority of lung adenocarcinoma express thyroid transcription factor-1 (TTF-1), but lack of TTF-1 expression correlates with worse prognosis. We investigated whether TTF-1 expression can correlate with a newly proposed IASLC/ATS/ERS lung adenocarcinoma classification and further stratify prognosis of histologic subtypes in stage I lung adenocarcinoma.
Design: H&E stained slides of 506 stage I lung adenocarcinoma patients (1995-2005) were reviewed. Tumors were classified into histologic subtypes according to the IASLC/ATS/ERS classification. We constructed a tissue microarray and performed immunohistochemistry for TTF-1. In all, 459 cases with adequate cores were available for TTF-1 expression analysis. Intensity of staining was scored as 0 (no expression), 1 (mild), 2 (intermediate), and 3 (strong). According to the intensity score, TTF-1 expression was divided into two groups: low (0-1) or high (2-3). Log-rank test was used to analyze the association between histologic variables and recurrence-free probability (RFP).
Results: High TTF-1 expression was identified in 100% (8/8) of adenocarcinoma in situ and minimally invasive adenocarcinoma, 96% (25/26) of lepidic predominant, 88% (113/129) of papillary, 87% (188/215) of acinar, 75% (9/12) of micropapillary, 77% (44/57) of solid, 44% (4/9) of invasive mucinous, and 33% (1/3) of colloid adenocarcinoma. High TTF-1 expression was more frequent in tumors with low architectural grade (p<0.001). The 5-year RFP of tumors with low TTF-1 expression (n=67, 69%) was lower than high TTF-1 expression (n=392, 85%, p=0.001). Among tumors with the acinar subtype, low TTF-1 expression (n=27) was associated with lower RFP (5-year RFP: 70%) compared to high TTF-1 expression (n=188, 86%, p=0.013). Among patients with other each histologic subtype, there was no significant difference of RFP between low and high TTF-1 expression.
Conclusions: TTF-1 expression was significantly correlated with architectural grade based on histologic subtype. In addition, TTF-1 expression correlated with recurrence, and further stratified the acinar predominant tumors into two prognostically distinct subsets.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 309, Tuesday Afternoon