Expression and prognostic implications of apoptosis-related proteins in locally unresectable non-small cell lung cancers.
BACKGROUND
Apoptosis related proteins in early staged NSCLC seem to have prognostic value. We studied the value of a combination of eight of those proteins in advanced NSCLC.


METHODS
Bronchoscopically procured tumor biopsies of NSCLC patients were stained immunohistochemically and rated for expression of eight different cellular proteins. Patients were treated with 60 Gy radiotherapy with or without carboplatin as radiosensitizer.


RESULTS
Apoptotic proteins in tumors that showed positive staining were the highest for Bax (99%), Fas (92%), FasL (87%), Rb (87%), p21(WAF1) (73%), and p53 (70%), and the lowest for c-myc (58%) and Bcl-2 (58%). In the Cox regression analysis Bcl-2 positivity (RR = 0.61, 95% CI, 0.37-0.98, p = 0.04) was predictive for overall survival. Only Bcl-2 staining percentage (RR(10) (RR associated with an increase in stained cells of 10%) = 0.93, 95% CI, 0.89-0.99), p53 (RR(10) = 0.94, 95% CI, 0.89-0.99) and FasL (RR(10) = 0.92, 95% CI, 0.86-0.99) were predictive for a longer progression-free survival. No specific constellation of apoptotic proteins was associated with tumor response.


CONCLUSIONS
Bcl-2 expression in tumor tissue of patients with unresectable NSCLC predicts a better overall survival, while Bcl-2, p53, and FasL expressions predict for a longer progression-free survival.
Fokkema
Eelco
E
Department of Pulmonary Diseases, University Medical Center Groningen, The Netherlands.
Timens
Wim
W
de Vries
Elisabeth G E
EG
de Jong
Steven
S
Fidler
Vaclav
V
Meijer
Coby
C
Groen
Harry J M
HJ
D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001706:Biopsy; D001999:Bronchoscopy; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D011013:Pneumonectomy; D011379:Prognosis; D012720:Severity of Illness Index; D015996:Survival Rate
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor