Immunohistochemical demonstration of apoptosis-regulated proteins, Bcl-2 and Bax, in resected non-small-cell lung cancers.
OBJECTIVE
Bcl-2 and Bax proteins regulate apoptosis independently, cooperatively, or both in vitro. The purpose of this study was to clarify the association between their expression with spontaneous apoptosis and various clinicopathologic features in patients with non-small-cell lung cancer (NSCLC).


METHODS
Bcl-2 protein, Bax protein, and spontaneous apoptosis were evaluated retrospectively in 70 resected specimens from NSCLC patients. Immunohistochemical (IHC) tests were used to assess the expression of Bcl-2 and Bax in the samples. The apoptotic index (AI) was also measured in these samples by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. We then evaluated the clinicopathologic features of all 70 samples and their relationships with malignancy.


RESULTS
Bcl-2 overexpression was significantly associated with male sex and squamous cell carcinoma (SCC). Bax overexpression was not associated with any clinicopathologic features. AI was significantly associated with SCC and negative nodal metastasis. No clear associations were found among Bcl-2 expression, Bax expression, and AI. Bcl-2/Bax ratios were not associated significantly with AI. Bcl-2, Bax, Bcl-2/Bax ratio, and the grading of AI did not have prognostic values.


CONCLUSIONS
Bcl-2 overexpression was significantly associated with SCC. Spontaneous apoptosis was significantly associated with SCC and with negative nodal metastasis. Apoptosis-regulated proteins, Bcl-2 and Bax, and AI lack significant associations with each other and prognostic values in patients with resected NSCLC.
Department of Surgery, Shinshu University School of Medicine, Asahi, Matsumoto, Japan. kyung@dl.dion.ne.jp
Takaomi
T
Hanaoka
Jun
J
Nakayama
Masayuki
M
Haniuda
Taka-Aki
TA
Sato
D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein