Comparison of DNA topoisomerase II alpha expression in small cell and nonsmall cell carcinoma of the lung. In search of a mechanism of chemotherapeutic response.

Abstract

Small cell carcinoma of the lung (SCLC) is distinguished from nonsmall cell carcinoma (NSCLC) by its exquisite initial sensitivity to chemotherapy. Antineoplastic drugs effective against SCLC include doxorubicin, etoposide, and others. Recently, the molecular target of these drugs has been identified as the alpha form of DNA topoisomerase II, which is important in DNA replication and in the separation of chromosomes during normal cellular division. In this study we compared DNA topoisomerase II alpha expression in SCLC and NSCLC by immunohistochemistry. We hypothesized that the sensitivity of SCLC and relative insensitivity of NSCLC to these chemotherapeutic agents stem from different frequencies of DNA topoisomerase II alpha expression. DNA topoisomerase II alpha expression was analyzed in 17 cases of SCLC and 24 cases of NSCLC by immunohistochemistry utilizing a monoclonal antibody recognizing the alpha isoform of DNA topoisomerase II. A topo II index was determined by dividing the number of tumor nuclei expressing DNA topoisomerase II by the total number of tumor nuclei counted. A significantly higher frequency of DNA topoisomerase II alpha expression was identified in SCLC (P < 0.001). The average topo II index for SCLC was 0.60 (range: 0.45-0.76) compared with NSCLC, 0.31 (range: 0.05-0.75). We conclude that DNA topoisomerase II alpha is expressed at a higher frequency in SCLC than in NSCLC, and that this expression is possibly involved in the response of SCLC to chemotherapeutic agents.