Lack of Correlation Between P-glycoprotein and Chemotherapy Resistance in Nasal NK/T-cell Lymphomas

• Published in: Leukemia & lymphoma Vol. 45; no. 9; pp. 1857 - 1864
• Main Authors: Kim, Gwi Eon, Yang, Woo-Ick, Lee, Sang-Wook, Rha, Sun Young, Chung, Hyun Cheol, Kim, Joo Hang, Cho, Jae Ho, Suh, Chang Ok, Yoo, Nae Choon, Roh, Jae Kyung, Hahn, Jee-Sook
• Format: Journal Article
• Language: English
• Published: United States Informa UK Ltd 01.09.2004; Taylor & Francis
• Subjects: Adult; Aged; ATP Binding Cassette Transporter, Subfamily B, Member 1 - immunology; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Chemotherapy; Drug Resistance, Neoplasm; Epstein-Barr virus; Female; Humans; Immunohistochemistry; Killer Cells, Natural - pathology; Lymphoma, T-Cell - drug therapy; Lymphoma, T-Cell - metabolism; Lymphoma, T-Cell - mortality; Lymphoma, T-Cell - pathology; Male; MDR; Middle Aged; NK/T-cell lymphomas; P-glycoprotein; Prognosis; Survival Rate
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428190410001693524

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.