Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences.
Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences.
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发表时间：
1994-07
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通讯作者：
Hoguen Kim;J. Jen;B. Vogelstein;S. Hamilton
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作者：
Hoguen Kim;J. Jen;B. Vogelstein;S. Hamilton
在散发性结直肠癌和遗传性非息肉病性结直肠癌综合征（HNPCC）患者的大多数肿瘤中，由于错配修复基因缺陷导致的重复核苷酸序列中的DNA复制错误（RERs）已被报道。我们在137例散发性II期和III期（Dukes' B和C期）结直肠癌的前瞻性系列中检测到18例（13%）RER。RER阳性病例的临床和病理特征与无RER的病例不同。RER阳性的癌症患者倾向于更年轻（60 +/- 5岁，范围22-83，对66 +/- 1，范围27-90，P = 0.2，方差不等），并且脾曲近端肿瘤明显占优势（17/18，94%对41/119，34%，P < 0.0001）。只有两名RE阳性患者（11%）有结直肠癌家族史。与41例RE阴性近端结肠癌相比，RE阳性癌的外生性生长更频繁（P = 0.04），大尺寸（P = 0.03），分化差（P = 0.0004），细胞外粘蛋白产生（P = 0.003）和克罗恩样淋巴反应（P = 0.003），免疫组化显示p53基因产物过度表达的频率有降低的趋势（3/17，18%，对18/41，44%，P = 0.06）。我们的结论是，散发性结直肠癌的一个子集具有独特的生物学特征，可能表明遗传性种系突变，从头种系突变，或参与HNPCC的错配修复基因的体细胞突变。
DNA replication errors (RERs) in repeated nucleotide sequences due to defective mismatch repair genes have been reported in a subset of sporadic colorectal carcinomas and in the majority of tumors from patients with hereditary nonpolyposis colorectal cancer syndrome (HNPCC). We detected RER in 18 cases (13%) in a prospective series of 137 sporadic stage II and III (Dukes' B and C) colorectal carcinomas. The clinical and pathological features of the RER-positive cases differed from those without RER. The patients with RER-positive cancers tended to be somewhat younger (60 +/- 5 years, range 22-83, versus 66 +/- 1, range 27-90, P = 0.2 with unequal variances) and had a marked preponderance of tumors proximal to the splenic flexure (17/18, 94%, versus 41/119, 34%, P < 0.0001). Only two RER-positive patients (11%) had a family history of colorectal cancer. In comparison to the 41 RER-negative proximal colonic cancers, RER-positive cancers had more frequent exophytic growth (P = 0.04), large size (P = 0.03), poor differentiation (P = 0.0004), extracellular mucin production (P = 0.003) and Crohn's-like lymphoid reaction (P = 0.003), and a trend toward less frequent p53 gene product overexpression by immunohistochemistry (3/17, 18%, versus 18/41, 44%, P = 0.06). We conclude that a subset of sporadic colorectal carcinomas has unique biological features that may indicate inherited germline mutation, de novo germline mutation, or somatic mutations of the mismatch repair genes involved in HNPCC.