COMPARISON OF DNA TOPOISOMERASE II-ALPHA EXPRESSION IN SMALL-CELL ANDNONSMALL CELL-CARCINOMA OF THE LUNG - IN SEARCH OF A MECHANISM OF CHEMOTHERAPEUTIC RESPONSE

BACKGROUND. Small cell carcinoma of the lung (SCLC) is distinguished f rom non-small cell carcinoma (NSCLC) by its exquisite initial sensitiv ity to chemotherapy. Antineoplastic drugs effective against SCLC inclu de doxorubicin, etoposide, and others. Recently, the molecular target of these drugs has been identified as the alpha form of DNA topoisomer ase II, which is important in DNA replication and in the separation of chromosomes during normal cellular division. In this study, we compar ed DNA topoisomerase II alpha expression in SCLC and NSCLC by immunohi stochemistry. We hypothesized that the sensitivity of SCLC and relativ e insensitivity of NSCLC to these chemotherapeutic agents stem from di fferent frequencies of DNA topoisomerase II alpha expression. METHODS. DNA topoisomerase II alpha expression was analyzed in 17 cases of SCL C and 24 cases of NSCLC by immunohistochemistry utilizing a monoclonal antibody recognizing the alpha isoform of DNA topoisomerase II. A top o II index was determined by dividing the number of tumor nuclei expre ssing DNA topoisomerase II by the total number of tumor nuclei counted . RESULTS. A significantly higher frequency of DNA topoisomerase II al pha 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). CONCLUSIONS. We conclude that DNA topoisomerase II alpha is expressed at a higher frequency in SCLC than in NSCLC, and t hat this expression is possibly involved in the response of SCLC to ch emotherapeutic agents. (C) 1996 American Cancer Society.