IMMUNOHISTOCHEMICAL P53 PROTEIN STATUS IN NONSMALL CELL LUNG-CANCER IS A PROMISING INDICATOR IN DETERMINING IN-VITRO CHEMOSENSITIVITY TO SOME ANTICANCER DRUGS

Background and Objectives: The tumor suppressor oncogene p53 abnormali ties have been closely associated with resistance or sensitivity of ca ncer cells to some chemotherapeutic agents. We examined the associatio n between p53 protein status in nonsmall cell lung cancer (NSCLC) and in vitro chemosensitivity to several chemotherapeutic agents. Methods: Using 146 surgically resected specimens of NSCLC, p53 status was immu nohistochemically evaluated, and in vitro chemosensitivity to 5-fluoro uracil (5-Fu), cisplatin (CDDP), mitomycin C (MMC), etoposide (VP-16), doxorubicin hydrochloride (ADM), and vindesine sulfate (VDS) was exam ined by a collagen gel-droplet embedded culture drug sensitivity test (CD-DST, Int J Oncol, 1997; 11:449). Results: Sixty-five of 146 materi als (45%) showed immunohistochemically abnormal p53 protein accumulati on in >10% of cancer cells within the tumor tissue, being regarded as p53+, whereas 81 (55%) were to p53-, in which no or less than 10% posi tive immunostaining cancer cells were detected. By CD-DST, the inciden ce of chemosensitive, borderline, and resistant p53-materials (N = 81) to 5-Fu was 37%(N = 30), 14%(N = 11), and 49%(N = 40), whereas that o f p53+ materials (N = 65) was 20%(N = 13), 6%(N = 4), and 74%(N = 48), respectively, showing that p53-materials were significantly more sens itive to 5-Fu than p53+ materials (P = 0.011), especially in the adeno carcinoma type. As similar borderline association between p53 protein status and in vitro chemosensitivity was also shown in ADM (P = 0.078) , but not in other chemoagents. Conclusions: Immunohistochemically det ected p53 protein status in NSCLC patients may be a promising indicato r in determining in vitro chemosensitivity to some anticancer drugs, e specially 5-Fu and ADM. (C) 1998 Wiley-Liss, Inc.