GLUCOSE-TRANSPORTER-TYPE-I-GENE AMPLIFICATION CORRELATES WITH SIALYL-LEWIS-X SYNTHESIS AND PROLIFERATION IN LUNG-CANCER

Increased glucose transport is a common characteristic of most tumors. To examine the role of elevated glucose uptake in lung cancer, we per formed PCR amplification of 2 facilitative glucose transporter genes ( GLUT1 and GLUT3) and immunohistochemical staining for GLUT1, prolifera ting cell nuclear antigen (PCNA), and sialyl Lewis x (sLe(x)) on tumor specimens from 327 patients with lung cancer who underwent surgical r esection from 1980 to 1993. To evaluate the relationship between GLUT, alpha-2,3-sialyltransferase (ST), and alpha-1,3-fucosyltransferase (F uc-T) genes, PCR amplification of the ST3N and Fuc-TYII also was perfo rmed. Amplification of GLUT1 was significantly greater than that of GL UT3. GLUT1 and GLUT3 amplification correlated with PCNA staining (p < 0.01). In addition, GLUT1 amplification correlated with the grading of sLe(x) staining as well as with the grading of GLUT1 staining (p < .0 3, p < 0.01). GLUT1 was co-amplified with ST3N and Fuc-TVII genes, whi ch are involved in the synthesis of sLe(x) (p < 0.01). The survival of patients whose tumors showed GLUT1 amplification was significantly sh orter than that of patients whose tumors did not (p < 0.01). In a mult ivariate analysis of survival, GLUT1 remained a statistically signific ant prognostic factor. Our results suggest that GLUT1 amplification ma y participate in sLe(x) synthesis as well as in proliferation, and may be of prognostic value in lung cancer. (C) 1997 Wiley-Liss, Inc.