[Correlation analysis among expression of ERCC-1, metallothionein, p53 and platinum resistance and prognosis in advanced non-small cell lung cancer].
OBJECTIVE
The molecular predictor for cisplatin sensitivity in advanced non-small cell lung cancer (NSCLC) is still an open question at present. The purpose of this study was to evaluate the relationship of the cisplatin sensitivity/prognosis with the expression of excision repair cross complement-1 (ERCC-1), metallothionein (MT), and p53 in the paraffin-embedded tissue of advanced non-small cell lung cancer (NSCLC).


METHODS
From January 1994 to December 2001, 51 pathologically confirmed advanced NSCLC patients were included. All patients received cisplatin contained regimen chemotherapy (Gemzar + DDP or NVB + DDP) as the first line treatment. At the same time, the tumor samples were collected and the expression of ERCC-1, MT, and p53 in the tumor samples were examined by immunohistochemical method. The response rates and survival data were analyzed according to the over-expression or not of these three parameters (negative group/over-expression group). The response rates were compared by Chi(2) test. Kaplan-Meier method and Cox proportional hazards model were used for survival analysis.


RESULTS
In these 51 patients, the expression rates of ERCC-1, MT, and p53 were 42.8%, 57.5%, and 37.8%, respectively. The response rates in negative group/over-expression group of ERCC-1, MT, and p53 were 33.3%/16.7%, 35.3%/27.3%, and 21.4%/35.3%, respectively (1.99, 1.29, and 0.61 times, respectively, P >0.05). The response rate in both ERCC-1 and MT negative group was 37.5%. In both ERCC-1 and MT over-expression (co-expression) group, the response rate was 14.3%. The former was 2.6 times of the latter (P >0.05). The average survival time in negative group/over-expression groups were 621/523 days (for ERCC-1), 556/479 days (for MT), 599/416 days (for p53), respectively. ERCC-1, MT, or p53 over-expression group showed poorer prognosis than those of negative group by Kaplan-Meier analysis. But in multivariate analysis, only p53 over-expression was an independent poor prognostic factor of survival time (Cox regression, P=0.009).


CONCLUSIONS
Whether over-expression of ERCC-1 and MT can be used as a molecular marker of cisplatin resistance in advanced NSCLC patients need further study. Over-expression of p53 predicates poor prognosis for patients with advanced NSCLC.
Huang
Pei-Yu
PY
Department of Medical Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, P.R.China.
Liang
Xiao-Man
XM
Lin
Su-Xia
SX
Luo
Rong-Zhen
RZ
Hou
Jing-Hui
JH
Zhang
Li
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D008668:Metallothionein; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin