School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Envoi Specialist Pathologists, Brisbane, Queensland, Australia.
Gut. 2017 Jan;66(1):97-106. doi: 10.1136/gutjnl-2015-310456. Epub 2015 Oct 15.
Sessile serrated adenomas (SSAs) are the precursors of at least 15% of colorectal carcinomas, but their biology is incompletely understood. We performed a clinicopathological and molecular analysis of a large number of the rarely observed SSAs with dysplasia/carcinoma to better define their features and the pathways by which they progress to carcinoma.
A cross-sectional analysis of 137 SSAs containing regions of dysplasia/carcinoma prospectively collected at a community GI pathology practice was conducted. Samples were examined for BRAF and KRAS mutations, the CpG island methylator phenotype (CIMP) and immunostained for MLH1, p53, p16, β-catenin and 0-6-methylguanine DNA methyltransferase (MGMT).
The median polyp size was 9 mm and 86.5% were proximal. Most were BRAF mutated (92.7%) and 94.0% showed CIMP. Mismatch repair deficiency, evidenced by loss of MLH1 (74.5%) is associated with older age (76.7 versus 71.0; p<0.0029), female gender (70% versus 36%; p<0.0008), proximal location (91% versus 72%; p<0.02), CIMP (98% versus 80%; p<0.02) and lack of aberrant p53 (7% versus 34%; p<0.001) when compared with the mismatch repair-proficient cases. Loss of p16 (43.1%) and gain of nuclear β-catenin (55.5%) were common in areas of dysplasia/cancer, irrespective of mismatch repair status.
SSAs containing dysplasia/carcinoma are predominantly small (<10 mm) and proximal. The mismatch repair status separates these lesions into distinct clinicopathological subgroups, although WNT activation and p16 silencing are common to both. Cases with dysplasia occur at a similar age to cases with carcinoma. This, together with the rarity of these 'caught in the act' lesions, suggests a rapid transition to malignancy following a long dwell time as an SSA without dysplasia.
无蒂锯齿状腺瘤（SSAs）是至少 15%结直肠癌的前体，但它们的生物学特性尚未完全阐明。我们对大量罕见的伴有异型增生/癌的 SSAs 进行了临床病理和分子分析，以更好地定义它们的特征以及向癌进展的途径。
对在社区胃肠病理实践中前瞻性收集的含有异型增生/癌的 137 个 SSAs 进行了横断面分析。对 BRAF 和 KRAS 突变、CpG 岛甲基化表型（CIMP）进行了检测，并对 MLH1、p53、p16、β-连环蛋白和 O-6-甲基鸟嘌呤 DNA 甲基转移酶（MGMT）进行了免疫染色。
息肉的中位大小为 9mm，86.5%位于近端。大多数 BRAF 突变（92.7%），94.0%显示 CIMP。错配修复缺陷，表现为 MLH1 缺失（74.5%）与年龄较大（76.7 岁比 71.0 岁；p<0.0029）、女性（70%比 36%；p<0.0008）、近端位置（91%比 72%；p<0.02）、CIMP（98%比 80%；p<0.02）和异常 p53 缺失（7%比 34%；p<0.001）相关。在存在或不存在错配修复缺陷的情况下，异型增生/癌区域中 p16 缺失（43.1%）和核β-连环蛋白获得（55.5%）均很常见。
含有异型增生/癌的 SSAs 主要为小（<10mm）和近端。错配修复状态将这些病变分为不同的临床病理亚组，尽管 WNT 激活和 p16 失活在两者中均很常见。伴有异型增生的病例与伴有癌的病例年龄相似。这与这些“被抓现行”病变的罕见性一起表明，在没有异型增生的情况下，SSA 作为无蒂锯齿状腺瘤存在很长一段时间后，会迅速向恶性转化。
