Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan.
Kyushu University Beppu Hospital, Beppu, Japan.
Clin Transl Gastroenterol. 2020 Dec;11(12):e00269. doi: 10.14309/ctg.0000000000000269.
In contrast to most colorectal carcinomas arising from pedunculated or sessile protruded adenomas, submucosal-invasive (pT1) colorectal carcinoma exhibiting a depressed surface (hereinafter, "depressed colorectal carcinoma," identified by means of high-definition endoscopy) is considered to be derived from depressed precursors. We hypothesized that depressed colorectal neoplasms have unique clinicopathological features different that are different from those of protruded and flat colorectal neoplasms.
We classified 27,129 colorectal neoplasms (909 pT1 carcinomas and 26,220 adenomas) resected between 2001 and 2017 into depressed (211 carcinomas and 109 adenomas), flat (304 carcinomas and 11,246 adenomas), and protruded subtypes (394 carcinomas and 14,865 adenomas) and compared their clinicopathological features. As exploratory analyses of pT1 carcinomas, we conducted whole-exome sequencing for 19 depressed and 8 protruded subtypes and RNA sequencing for 8 depressed and 8 protruded subtypes.
pT1 carcinomas were more common in depressed lesions (66%) than in protruded (2.6%) and flat lesions (2.6%) (P < 0.001). Compared with nondepressed pT1 carcinomas, depressed pT1 carcinomas were positively correlated with lymphovascular invasion, tumor budding, and massive submucosal invasion and inversely correlated with the presence of an adenoma component (all P < 0.001). Depressed adenomas were more likely to contain high-grade dysplasia than nondepressed adenomas (49% vs 11%, P < 0.001). A KRAS mutation was observed only in one of the 19 depressed pT1 carcinomas. Relative to protruded carcinomas, depressed carcinomas generally exhibited higher expression of genes related to angiogenesis and epithelial-mesenchymal transition.
Depressed colorectal neoplasms may harbor a unique combination of malignant histopathological phenotypes and molecular features.
与大多数源自有蒂或无蒂突出性腺瘤的结直肠腺癌相反，黏膜下浸润（pT1）结直肠腺癌表现为凹陷表面（以下简称“凹陷性结直肠腺癌”，通过高清内镜识别）被认为源自凹陷前体。我们假设凹陷性结直肠肿瘤具有独特的临床病理特征，与突出性和平坦性结直肠肿瘤不同。
我们将 2001 年至 2017 年间切除的 27129 个结直肠肿瘤（909 个 pT1 癌和 26220 个腺瘤）分为凹陷型（211 个癌和 109 个腺瘤）、平坦型（304 个癌和 11246 个腺瘤）和突出型，并比较其临床病理特征。作为对 pT1 癌的探索性分析，我们对 19 个凹陷型和 8 个突出型进行了全外显子测序，对 8 个凹陷型和 8 个突出型进行了 RNA 测序。
pT1 癌在凹陷性病变（66%）中比突出性（2.6%）和平坦性病变（2.6%）更常见（P<0.001）。与非凹陷性 pT1 癌相比，凹陷性 pT1 癌与淋巴管血管侵犯、肿瘤芽生和广泛黏膜下浸润呈正相关，与腺瘤成分的存在呈负相关（均 P<0.001）。凹陷性腺瘤比非凹陷性腺瘤更有可能含有高级别异型增生（49% vs 11%，P<0.001）。在 19 个凹陷性 pT1 癌中仅观察到一个 KRAS 突变。与突出性癌相比，凹陷性癌通常表现出更高的血管生成和上皮-间充质转化相关基因的表达。
凹陷性结直肠肿瘤可能具有独特的恶性组织病理学表型和分子特征组合。
