Prognostic relevance of TTF-1 and MMP-9 expression in advanced lung adenocarcinoma.
BACKGROUND
The thyroid transcription factor-1 (TTF-1) is a tissue-specific transcription factor that could play an important role in cell differentiation and morphogenesis of lung tumors. Matrix metalloproteinase-9 (MMP-9) is a protease commonly expressed in non-small cell lung cancer, conferring angiogenic and metastatic potential.


METHODS
We assessed TTF-1 and MMP-9 tumor expression by immunohistochemistry in 51 patients with lung adenocarcinoma, stage IIIB or IV, treated with platinum regimens. A bicategorical prognostic model was obtained using the Kaplan-Meier method, Cox regression, and conjunctive consolidation.


RESULTS
The median expression of TTF-1 was 30.0% (range: 0-85.9%). All tumors expressed MMP-9 (median: 78.7%; range: 15.2-96.1%). Median survival was 41.6 weeks, with estimated 1- and 2-year survival rates of 45.0% and 22.0%, respectively. Poor performance status (Karnofsky scale) - hazards ratio (HR): 1.03, 95% confidence interval (CI): 1.01-1.06; low TTF-1 expression (<40%) - HR: 4.00, 95% CI: 1.75-9.09; and high MMP-9 expression (> or =80%) - HR: 2.82, 95% CI: 1.30-6.08 were independent prognostic factors. Patients could be stratified in three death risk groups according to markers expression: low risk (high TTF-1 and low MMP-9; median survival: 127.6 weeks), intermediate risk (low TTF-1 or high MMP-9; median survival: 39.0 weeks); and high risk (low TTF-1 and high MMP-9; median survival: 16.4 weeks).


CONCLUSIONS
TTF-1 and MMP-9 tumor expression as detected by immunohistochemistry may allow identification of different, clinically meaningful, prognostic groups of advanced lung adenocarcinoma patients treated with platinum regimens.
Martins
Sandro J
SJ
Pulmonary Division, School of Medicine, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar 255, 05403-000 São Paulo, Brazil. sjmartins@yahoo.com
Takagaki
Teresa Y
TY
Silva
Alecsander G P
AG
Gallo
Célia P
CP
Silva
Fernando B A
FB
Capelozzi
Vera L
VL
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014157:Transcription Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C504003:TTF1 protein, human; D014157:Transcription Factors; D020780:Matrix Metalloproteinase 9