Yantiss Rhonda K, Panczykowski Andrea, Misdraji Joseph, Hahn Hejin P, Odze Robert D, Rennert Hanna, Chen Yao-Tseng
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10021, USA.
Am J Surg Pathol. 2007 Nov;31(11):1742-53. doi: 10.1097/PAS.0b013e31806bee6d.
Serrated colorectal polyps often show DNA hypermethylation and/or BRAF mutations and have been implicated in the "serrated neoplastic pathway." Although similar lesions occur in the appendix, they have never been systematically investigated. We evaluated a study group of 56 serrated polyps, a control group of 17 mucinous cystadenomas, and 4 adenocarcinomas with adjacent serrated polyps of the appendix to better understand their pathogenesis. The study cases were classified as nondysplastic or dysplastic serrated polyps and evaluated for MLH-1, MSH-2, MGMT, beta-catenin, p53, and Ki-67 expression, BRAF and KRAS mutations, and microsatellite instability. Serrated polyps usually occurred in older adults with no sex predilection. Most (59%) lacked dysplasia, but all showed similar molecular features, regardless of the degree of dysplasia present. Decreased MLH-1 (50%, P<0.001) and/or MGMT (59%, P<0.001) expression and BRAF (29%, P=0.007) mutations were significantly more common in serrated polyps, but BRAF mutations were detected in a minority of the extracted DNA in 15/16 cases. Of the 28 cases with decreased MLH-1 expression, none showed high-frequency microsatellite instability. Loss of MLH-1 (25%) or MGMT (50%) expression and BRAF or KRAS mutations (50%) were inconsistently present in adenocarcinomas and were not identified in combination in any cases. We conclude that molecular features of the "serrated neoplastic pathway" are present with similar frequencies among dysplastic and nondysplastic serrated appendiceal polyps and are not highly prevalent in adjacent carcinomas. These features, including BRAF mutations, may be more closely related to a serrated morphology in appendiceal polyps rather than biologically important changes.
锯齿状结直肠息肉常表现出DNA高甲基化和/或BRAF突变，并与“锯齿状肿瘤发生途径”有关。虽然阑尾中也会出现类似病变，但从未进行过系统研究。我们评估了一个由56个锯齿状息肉组成的研究组、一个由17个黏液性囊腺瘤组成的对照组以及4个伴有阑尾相邻锯齿状息肉的腺癌，以更好地了解它们的发病机制。研究病例分为非发育异常或发育异常的锯齿状息肉，并评估MLH-1、MSH-2、MGMT、β-连环蛋白、p53和Ki-67的表达、BRAF和KRAS突变以及微卫星不稳定性。锯齿状息肉通常发生在老年人中，无性别倾向。大多数（59%）无发育异常，但无论发育异常程度如何，所有息肉都表现出相似的分子特征。MLH-1表达降低（50%，P<0.001）和/或MGMT表达降低（59%，P<0.001）以及BRAF突变（29%，P=0.007）在锯齿状息肉中显著更常见，但在15/16例病例中，仅少数提取的DNA检测到BRAF突变。在28例MLH-1表达降低的病例中，无一例表现出高频微卫星不稳定性。腺癌中MLH-1（25%）或MGMT（50%）表达缺失以及BRAF或KRAS突变（50%）存在不一致情况，且在任何病例中均未同时出现。我们得出结论，“锯齿状肿瘤发生途径”的分子特征在发育异常和非发育异常的阑尾锯齿状息肉中出现频率相似，在相邻癌中并不普遍。这些特征，包括BRAF突变，可能与阑尾息肉的锯齿状形态更密切相关，而非生物学上重要的改变。
