Clinical significance of apoptotic index in non-small cell lung cancer: correlation with p53, mdm2, pRb and p21WAF1/CIP1 protein expression.
OBJECTIVE
The aim of this study was to assess the prognostic relevance of apoptotic index (AI), considered alone or together with expression of several proteins controlling G1 check point (p53, mdm2, pRb and p21WAF1/CIP1) in non-small cell lung cancer (NSCLC) patients.


METHODS
Study group included 50 NSCLC patients who underwent curative pulmonary resection. Apoptosis was detected with the use of TUNEL technique and AI was defined as the number of apoptotic cells per 1,000 tumor cells. The expression of p53, mdm2, pRb and p21WAF1/CIP1 was assessed immunohistochemically.


RESULTS
The mean and median AI calculated for all 50 patients was 14 and 9, respectively. Patients with lower (<14) and higher (> or =14) AI constituted 35 (70%) and 15 (30%) of cases, respectively. AI was not correlated with patient clinical characteristics, and expression of p53, pRb and p21WAF1/CIP1 . However, lower AI was correlated with over-expression of mdm2 protein (P=0.04). Median survival for patients with lower and higher AI was 43 months and 22 months, respectively, and 5-year survival probability-60 and 25%, respectively (P=0.03). In multivariate analysis, the only variable associated with shortened survival was AI (P=0.03, HR=2.9, 95% CI 1.95-3.86).


CONCLUSIONS
These results suggest that AI correlates with mdm2 protein expression and influences survival in NSCLC.
Dworakowska
D
D
Department of Internal Medicine, Endocrinology and Haemostatic Disorders, Medical University of Gdańsk, Gdańsk, Poland. ddw@amg.gda.pl
Jassem
E
E
Jassem
J
J
Karmoliński
A
A
Dworakowski
R
R
Wirth
T
T
Gruchała
M
M
Rynkiewicz
A
A
Skokowski
J
J
Yla-Herttuala
S
S
Jaśkiewicz
K
K
Czestochowska
E
E
D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D016019:Survival Analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2