title: Lack of correlation between P-glycoprotein and chemotherapy resistance in nasal NK/T-cell lymphomas.
abstract: Thirty patients with nasal natural killer (NK)/T-cell lymphoma, who underwent systemic chemotherapy with or without involved-field radiotherapy between 1993 and 1998, were retrospectively reviewed to determine the clinical significance of P-glycoprotein immunohistochemically identified in tumor specimens. Eighty percent of previously untreated patients expressed P-glycoprotein. According to P-glycoprotein immunoreactivity, all patients with nasal NK/T-cell lymphoma were divided into 2 groups; (a) P-glycoprotein-negative group (N = 6) and (b) P-glycoprotein-positive group (N = 24). There was no significant difference in clinical profiles between both groups. Regardless of the P-glycoprotein expressions, Epstein-Barr virus genomes were almost identically detected in patients of the 2 groups. Contrary to our expectations, however, P-glycoprotein expressions were not found to be a strong predictor of chemotherapy resistance. Although 2 (33%) of 6 P-glycoprotein-negative patients and 10 (42%) of the 24 P-glycoprotein-positive patients showed a favorable response to systemic chemotherapy, 4 (67%) of 6 P-glycoprotein-negative patients did not achieve complete response (CR) to chemotherapy, which led to an early death, whereas 4 (17%) of the 24 P-glycoprotein-positive patients achieved CR to chemotherapy despite positive P-glycoprotein immunoreactivity. Overall, there were no significant differences in either CR rate or the response rate of patients in the two groups. Overall 5-year actuarial survival and disease-free survival for all patients were 44% and 47%, respectively, but no differences in survival rates were observed between 2 groups. (5-year actuarial survival rate: 33% for the P-glycoprotein-negative, 50% for the P-glycoprotein-positive) (P = 0.7093, log-rank). On univariate and multivariate analyses, P-glycoprotein expressions by immunohistochemical study were not found to be an important prognostic factor. Given these observations, we conclude that the molecular mechanisms of resistance to chemotherapy in nasal NK/T-cell lymphoma patients are not entirely dependent on P-glycoprotein, and that other complex mechanisms of drug action and resistance may be likely to be involved.
authors.affiliation: Department of Radiation Oncology, Brain Korea 21 Project for Medical Science, Yonsei University, College of Medicine, Yonsei Cancer Center, Seoul, Korea. gekim@yumc.yonsei.ac.kr
authors.forename: Gwi Eon
authors.initials: GE
authors.lastname: Kim
authors.forename: Woo-Ick
authors.initials: WI
authors.lastname: Yang
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Lee
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
authors.forename: Joo Hang
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Cho
authors.forename: Chang Ok
authors.initials: CO
authors.lastname: Suh
authors.forename: Nae Choon
authors.initials: NC
authors.lastname: Yoo
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Roh
authors.forename: Jee-Sook
authors.initials: JS
authors.lastname: Hahn
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D000368:Aged; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1