食管癌患者根治性食管切除术后短期和长期生存率的基因改变。
Genetic alterations in patients with esophageal cancer with short- and long-term survival rates after curative esophagectomy.
作者信息
Shimada Y, Imamura M, Shibagaki I, Tanaka H, Miyahara T, Kato M, Ishizaki K
机构信息
Department of Surgery & Surgical Basic Science Graduate School of Medicine, Kyoto University, Japan.
出版信息
Ann Surg. 1997 Aug;226(2):162-8. doi: 10.1097/00000658-199708000-00007.
OBJECTIVE
The objective of this study was to ascertain the exact relation between specific oncogenes and long- and short-term survival rates in patients with esophageal cancer.
SUMMARY BACKGROUND DATA
Recent developments in molecular biology have shown that several oncogenes and suppressor genes are involved in the development of esophageal cancer. However, the role of these genes still is unknown.
METHODS
The clinical outcome of 84 cases of R0-resected esophageal carcinomas (from 1986-1993) and the molecular and biologic characteristics of these tumors were studied. The patients studied were divided into three groups, which were designated as follows: shortest term survivors (up to 6 months), short-term survivors (7-12 months), and long-term survivors (>5 years). These groups included 23, 17, and 44 subjects, respectively. For the genomic analysis, CyclinD1, int-2, murine double minute 2 (MDM2), retinoblastoma, p53, adenomatous polyposis coli (APC), deleted in colorectal carcinoma (DCC), and human papillomavirus were studied in these patients. The regrowth capability of primary cultures and the clinicopathologic characteristics of these patients also were analyzed.
RESULTS
The CyclinD1 and int-2 genes, which are located in the 11q13 chromosome, and the MDM2 gene were related to short survival. However, the p53 mutation and human papillomavirus infection were not related to short-term survival. The average ratio of genomic abnormalities to genes examined was higher in the shortest and short-term survival groups than in the long-term survival group. Regrowth capability in primary cultures also was related to short-term survival. Among the long-term survival patients, 7 (16%) of 44 cases suffered further cancer after esophagectomy.
CONCLUSIONS
These results suggest that the 11q13 amplicon and MDM2 may play an important role in the progression of esophageal cancer, and an accumulation of genomic abnormalities may result in poor prognosis. Careful follow-up testing for double cancer is needed in long-term survivors of esophageal cancer.
目的
本研究的目的是确定特定癌基因与食管癌患者长期和短期生存率之间的确切关系。
总结背景数据
分子生物学的最新进展表明，几种癌基因和抑癌基因与食管癌的发生有关。然而，这些基因的作用仍然未知。
方法
研究了84例R0切除的食管癌患者（1986 - 1993年）的临床结局以及这些肿瘤的分子和生物学特征。所研究的患者分为三组，具体如下：短期生存者（存活期长达6个月）、中期生存者（7 - 12个月）和长期生存者（>5年）。这些组分别包括23、17和44名受试者。对于基因组分析，研究了这些患者的细胞周期蛋白D1、int-2、小鼠双微体2（MDM2）、视网膜母细胞瘤、p53、腺瘤性息肉病基因（APC）、结直肠癌缺失基因（DCC）和人乳头瘤病毒。还分析了原代培养物的再生长能力以及这些患者的临床病理特征。
结果
位于11q13染色体上的细胞周期蛋白D1和int-2基因以及MDM2基因与短期生存相关。然而，p53突变和人乳头瘤病毒感染与短期生存无关。短期和中期生存组中基因组异常与所检测基因的平均比率高于长期生存组。原代培养物中的再生长能力也与短期生存相关。在长期生存患者中，44例中有7例（16%）在食管切除术后发生了再次癌症。
结论
这些结果表明，11q13扩增子和MDM2可能在食管癌进展中起重要作用，基因组异常的积累可能导致预后不良。食管癌长期生存者需要仔细进行双原发癌的随访检测。
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