Bcl-2 and β1-integrin predict survival in a tissue microarray of small cell lung cancer.
BACKGROUND
Survival in small cell lung cancer (SCLC) is limited by the development of chemoresistance. Factors associated with chemoresistance in vitro have been difficult to validate in vivo. Both Bcl-2 and β(1)-integrin have been identified as in vitro chemoresistance factors in SCLC but their importance in patients remains uncertain. Tissue microarrays (TMAs) are useful to validate biomarkers but no large TMA exists for SCLC. We designed an SCLC TMA to study potential biomarkers of prognosis and then used it to clarify the role of both Bcl-2 and β(1)-integrin in SCLC.


METHODS
A TMA was constructed consisting of 184 cases of SCLC and stained for expression of Bcl-2 and β(1)-integrin. The slides were scored and the role of the proteins in survival was determined using Cox regression analysis. A meta-analysis of the role of Bcl-2 expression in SCLC prognosis was performed based on published results.


RESULTS
Both proteins were expressed at high levels in the SCLC cases. For Bcl-2 (n=140), the hazard ratio for death if the staining was weak in intensity was 0.55 (0.33-0.94, P=0.03) and for β(1)-integrin (n=151) was 0.60 (0.39-0.92, P=0.02). The meta-analysis showed an overall hazard ratio for low expression of Bcl-2 of 0.91(0.74-1.09).


CONCLUSIONS
Both Bcl-2 and β(1)-integrin are independent prognostic factors in SCLC in this cohort although further validation is required to confirm their importance. A TMA of SCLC cases is feasible but challenging and an important tool for biomarker validation.
Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
M H
MH
Lawson
N M
NM
Cummings
D M
DM
Rassl
S L
SL
Vowler
M
M
Wickens
W J
WJ
Howat
J D
JD
Brenton
G
G
Murphy
R C
RC
Rintoul
D000368:Aged; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000032:analysis*; D008175:Lung Neoplasms / Q000737:chemistry / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D055752:Small Cell Lung Carcinoma / Q000737:chemistry / Q000401:mortality*; D046888:Tissue Array Analysis
D019012:Integrin beta1; D019253:Proto-Oncogene Proteins c-bcl-2