Expression of DNA topoisomerase IIα and topoisomerase IIβ genes predicts survival and response to chemotherapy in patients with small cell lung cancer

摘要: Drug resistance is a major problem in patients with small cell lung cancer; fact, most die of resistant disease, despite an initial response. Several markers drug have been described preclinical models, but the mechanism cancer remains unknown. The objective this study was to evaluate role expression number resistance, proliferation, and apoptosis relation response chemotherapy survival cancer. Tumor samples were derived from 93 previously untreated who randomized Phase III receive cyclophosphamide, epirubicine, etoposide or epirubicine vincristine alternating carboplatin etoposide. Paraffin-embedded samples, primary tumor site prior chemotherapy, analyzed by immunohistochemistry for implicated [topoisomerase (topo) IIα, topo IIβ, multidrug resistance-associated protein], (p53, p21, bcl-2), proliferation (Ki67). Response prediction χ 2 test logistic regression analysis; overall disease-free curves compared log-rank Cox analysis. Shorter observed extensive disease ( P = 0.037) poorer performance status 0.028) whose tumors expressed high IIα levels 0.01) Ki67 0.024). By multivariate analysis, following factors found be predictive worse survival: Ki67, bcl-2; male sex; disease. High IIβ lower complete rate. No relationship between apoptotic pathway MRP observed. In conclusion, survival, rates. Furthermore, probability bcl-2-positive tumors. Immunohistochemical assessment these diagnostic biopsies may give important prognostic information help selecting categories new therapeutic strategies.