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 metallothionen (MT), proliferating cell nuclear antigen (PCNA), p53, and retinoblastoma gene product (RBGP) in biopsy samples from 58 patients with SCLC prior to standard chemotherapy. The objective was to study the correlation between MT and other molecular markers in SCLC and correlate these data with the clinical outcome of patients. The authors studied 28 short-term survivors (STS; survival < 24 months) and 30 long-term survivors (LTS; survival > 24 months).


RESULTS
In line with expectations, the authors found a strong inverse association 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 27 LTS) were positive for PCNA, 28 patients (48%; 16 STS and 12 LTS) were positive for p53, and only 6 patients (10%; 1 STS and 5 LTS) showed positivity for RBGP. On comparing the percent positivity of various markers in the two 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 group. However, only the difference in expression of MT between the two survivor groups was statistically significant (Fisher exact test; P = 0.034). Multivariable 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-square test; P = 0.001).


CONCLUSIONS
In this study, of the molecular markers studied, the authors demonstrated that only MT overexpression was independently predictive of short-term survival in patients with SCLC undergoing chemotherapy.
Joseph
M G
MG
Department of Pathology, University of Western Ontario, London, Ontario, Canada. mariamma.joseph@sjhc.london.on.ca
Banerjee
D
D
Kocha
W
W
Feld
R
R
Stitt
L W
LW
Cherian
M G
MG
D000328:Adult; D000368:Aged; D015415:Biomarkers; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D015415:Biomarkers; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D008668:Metallothionein