Metallothionein expression in patients with small cell carcinoma of the lung - Correlation with other molecular markers and clinical outcome

BACKGROUND. Patients with small cell carcinoma of the lung (SCLC) are known to have an extremely poor prognosis, with a 5-year survivor rate of only 5 %. Chemotherapeutic drug resistance is a major obstacle to curative therapy in patients with SCLC. METHODS. The authors evaluated retrospectively the expression of metallothi onen (MT), proliferating cell nuclear antigen (PCNA), p53, and retinoblasto ma gene product (RBGP) in biopsy samples from 58 patients with SCLC prior t o standard chemotherapy. The objective was to study the correlation between MT and other molecular markers in SCLC and correlate these data with the c linical outcome of patients. The authors studied 28 short-term survivors (S TS; survival < 24 months) and 30 long-term survivors (LTS; survival > 24 mo nths). RESULTS. In line with expectations, the authors found a strong inverse asso ciation between stage and survival. Of 58 patients with SCLC, 26 patients ( 45%; 17 STS and 9 LTS) showed MT expression, 55 patients (94%; 28 STS and 2 7 LTS) were positive for PCNA, 28 patients (48%; 16 STS and 12 LTS) were po sitive for p53, and only 6 patients (10%; 1 STS and 5 LTS) showed positivit y for RBGP. On comparing the percent positivity of various markers in the t wo survivor groups, there was greater frequency of expression of MT, PCNA, and p53 and lower RBGP expression in the STS group compared with the LTS gr oup. However, only the difference in expression of MT between the two survi vor groups was statistically significant (Fisher exact test; P = 0.034). Mu ltivariable analysis using a logistic regression model showed a significant association between MT expression and patient survival after adjusting for disease stage (chi-square test; P = 0.022). There was also a statistically significant association between MT expression and p53 expression (chi-squa re test; P = 0.001). CONCLUSIONS. In this study, of the molecular markers studied, the authors d emonstrated that only MT overexpression was independently predictive of sho rt-term survival in patients with SCLC undergoing chemotherapy. (C) 2001 Am erican Cancer Society.