Transcription factor expression aids stage I lung cancer prognosis

By Liam Davenport, medwireNews Reporter

Expression of thyroid transcription factor-1 (TTF-1) is an independent predictor for recurrence of stage I lung adenocarcinoma and allows intermediate-grade tumors to be split into two prognostic subsets, scientists have found.

Prasad Adusumilli, from Memorial Sloan-Kettering Cancer Center in New York, USA, and colleagues also report that TTF-1 expression correlates with the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) tumor classification.

They write in Cancer: "One limitation to using the IASLC/ATS/ERS classification is that the majority of patients are classified as having intermediate-grade tumors. Therefore, it is necessary to recognize poor prognostic factors for this group of patients."

They add: "Since the morphologic assessment of H&E [hematoxylin and eosin]-stained slides and immunohistochemical analysis have become routine in clinical practice,prognostic stratification using the IASLC/ ATS/ERS classification and TTF-1 immunohistochemistry can be readily implemented in the treatment of patients with lung adenocarcinoma."

The team reviewed medical records for 452 patients diagnosed with pathologic stage I solitary lung adenocarcinoma who underwent surgical resection between 1995 and 2005 and found that 73 patients had disease recurrence, while102 without documented recurrence. The median follow-up period for patients without recurrence was 57.3 months.

TTF-1 expression was recorded in 92% of patients. The rate of positivity significantly differed between IASLC/ATS/ERS low- (adenocarcinoma in situ, minimally invasive adenocarcinoma, or lepidic-predominant), intermediate- (papillary-predominant or acinar-predominant) , and high-grade (micropapillary-predominant, solid-predominant, colloid-predominant, or invasive mucinous) tumors, at 100%, 95%, and 80%, respectively.

Thirty-four tumors had a TTF-1 expression score of 0, 32 had a score of 1, 195 had a score of 2, and 191 had a score of 3. The 5-year cumulative incidence of recurrence (CIR) was significantly higher for patients with a TTF-1 expression score of 0 than for those with scores of 1, 2, or 3, at 40% versus 19%, 17%, and 12%, respectively.

The 5-year CIR for patients negative for TTF-1 expression was 40%, significantly higher than the 15% calculated for TTF-1-positive patients. Among patients with intermediate-grade tumors, negative TTF-1 expression conferred a significantly greater 5-year CIR than positive expression, at 45% versus 15%.

On multivariate analysis, TTF-1 expression was associated with a significant increased risk for disease recurrence, at a hazard ratio of 2.25. TTF-1 expression was an independent predictor for recurrence in intermediate-grade tumors, at a hazard ratio of 3.84.

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