GENETIC ALTERATIONS IN PATIENTS WITH ESOPHAGEAL CANCER WITH SHORT-TERM AND LONG-TERM SURVIVAL RATES AFTER CURATIVE ESOPHAGECTOMY

Objective The objective of this study was to ascertain the exact relat ion between specific oncogenes and long-and short-term survival rates in patients with esophageal cancer. Summary Background Data Recent dev elopments in molecular biology have shown that several oncogenes and s uppressor genes are involved in the development of esophageal cancer. However, the role of these genes still is unknown. Methods The clinica l outcome of 84 cases of RO-resected esophageal carcinomas (from 1986- 1993) and the molecular and biologic characteristics of these tumors w ere studied. The patients studied were divided into three groups, whic h were designated as follows: shortest term survivors (up to 6 months) , short-term survivors (7-12 months), and long-term survivors (>5 year s). These groups included 23, 17, and 44 subjects, respectively, For t he genomic analysis, CyclinD1, int-2, murine double minute 2 (MDM2), r etinoblastoma, p53, adenomatous polyposis coli (APC), deleted in color ectal carcinoma (DCC), and human papillomavirus were studied in these patients. The regrowth capability of primary cultures and the clinicop athologic characteristics of these patients also were analyzed. Result s The CyclinD1 and int-2 genes, which are located in the 11q13 chromos ome, and the MDM2 gene were related to short survival. However, the p5 3 mutation and human papillomavirus infection were not related to shor t-term survival. The average ratio of genomic abnormalities to genes e xamined was higher in the shortest and short-term survival groups than in the long-term survival group. Regrowth capability in primary cultu res also was related to short-term survival. Among the long-term survi val patients, 7 (16%) of 44 cases suffered further cancer after esopha gectomy. Conclusions These results suggest that the 11q13 amplicon and MDM2 may play an important role in the progression of esophageal canc er, and an accumulation of genomic abnormalities may result in poor pr ognosis. Careful follow-up testing for double cancer is needed in long -term survivors of esophageal cancer.