p53-regulated GML gene expression in non-small cell lung cancer: a promising relationship to cisplatin chemosensitivity

The GML gene (glycosylphosphatidylinositol-anchored molecule-like protein g ene) is a novel gene specifically induced by wild-type p53. which may parti cipate in cell cycle control or the cell apoptotic pathway. Recent experime nts suggest that the expression of this never gene in cancer cells is close ly associated with sensitivity to certain anticancer drugs. To elucidate th e role of the gene expression in cisplatin (CDDP) chemosensitivity of non-s mall cell lung cancer (NSCLC), 30 surgically resected materials were examin ed by reverse transcriptase-polymerase chain reaction (RT-PCR). GML gene ex pression was detected in 9 (30%) samples. Its incidence was significantly h igher in immunohistochemically p53-negative (P = 0.040) or wild-type p53 ti ssues (P = 0.041). On in vitro chemosensitivity testing using 29 primary ti ssues, six samples with GML gene expression showed good sensitivity to CDDP . In particular, in tissues with immunohistochemically p53-negative accumul ation. those with GML gene expression showed significantly better in vitro sensitivity to CDDP (P = 0.012). Clinically a good response to CDDP-based c hemo(thermo)therapy for NSCLC patients with tumour residue or recurrence, w as observed only in those with p53-negative accumulation and GML gene expre ssion, in agreement with br vitro results. Thus. although the number of tes ted samples was small, GML gene expression is commonly detected in immunohi stochemically p53-negative NSCLCs in close association with good sensitivit y to CDDP. GML gene expression analysis may serve as a predictor of CDDP-ba sed chemotherapy for patients with NSCLC. (C) 2000 Elsevier Science Ltd. Al l rights reserved.