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 abnormalities have been closely associated with resistance or sensitivity of cancer cells to some chemotherapeutic agents. We examined the association 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 immunohistochemically evaluated, and in vitro chemosensitivity to 5-fluorouracil (5-Fu), cisplatin (CDDP), mitomycin C (MMC), etoposide (VP-16), doxorubicin hydrochloride (ADM), and vindesine sulfate (VDS) was examined by a collagen gel-droplet embedded culture drug sensitivity test (CD-DST, Int J Oncol, 1997;11:449). Results Sixty-five of 146 materials (45%) showed immunohistochemically abnormal p53 protein accumulation 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% positive immunostaining cancer cells were detected. By CD-DST, the incidence 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 of p53+ materials (N=65) was 20%(N=13), 6%(N=4), and 74%(N=48), respectively, showing that p53− materials were significantly more sensitive to 5-Fu than p53+ materials (P=0.011), especially in the adenocarcinoma 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 detected p53 protein status in NSCLC patients may be a promising indicator in determining in vitro chemosensitivity to some anticancer drugs, especially 5-Fu and ADM. J. Surg. Oncol. 1998;68:19–24. © 1998 Wiley-Liss, Inc.