Prognostic significance of mucin and p53 expression in stage IB non-small cell lung cancer: a laboratory companion study to CALGB 9633.
BACKGROUND
Cancer and Leukemia Group B 9633 was a phase III trial that randomized patients with stage IB non-small cell lung cancer to observation or four cycles of carboplatin and paclitaxel. A statistically significant effect in favor of adjuvant chemotherapy was seen for disease-free survival (DFS) and overall survival (OS) in the subgroup of patients with tumors > or =4 cm. A laboratory companion study was conducted to see whether molecular and clinical factors could provide additional prognostic information.


METHODS
Formalin-fixed, paraffin-embedded blocks were obtained for 250 of the 344 patients enrolled. Immunohistochemical staining for bcl-2, p53, blood group antigen A, and mucin was correlated with DFS and OS.


RESULTS
The prevalence of the markers was bcl-2, 17%; p53, 47%; blood group antigen A, 25%; and mucin, 45%. Univariate analysis for DFS showed a statistically significant effect for the presence of mucin (p = 0.0005) and p53 (p = 0.05) and for OS showed a significant effect for mucin (p = 0.0005). In the multivariate Cox model, there was a statistically significant association between shorter DFS and presence of mucin (p = 0.002; hazard ratio [HR] 2.05) and p53 (p = 0.003; HR 1.95) and between shorter OS and presence of mucin (p = 0.004; HR 2.03) and p53 (p = 0.0005; HR 2.30). Of the clinical factors, male gender and larger tumor volume were also significant adverse prognostic factors (p 0.05).


CONCLUSIONS
A statistically significant association between shorter DFS and OS was seen for the patients with p53 protein expression, mucin expression, male gender, and larger tumors in this cohort of patients with stage IB non-small cell lung cancer treated on Cancer and Leukemia Group B 9633.
Graziano
Stephen L
SL
Department of Medicine, State University of New York Upstate Medical University, Syracuse, New York 13210, USA. grazians@upstate.edu
Gu
Lin
L
Wang
Xiaofei
X
Tatum
Arthur H
AH
Vollmer
Robin T
RT
Strauss
Gary M
GM
Kratzke
Robert
R
Dudek
Arkadiusz Z
AZ
Vokes
Everett E
EE
Green
Mark R
MR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis; D018572:Disease-Free Survival; D004720:Endonucleases / Q000032:analysis; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000032:analysis*; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D004268:DNA-Binding Proteins; D009077:Mucins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C071447:ERCC1 protein, human; D004720:Endonucleases