Depressed Colorectal Cancer: A New Paradigm in Early Colorectal Cancer.
Depressed Colorectal Cancer: A New Paradigm in Early Colorectal Cancer.
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DOI：
10.14309/ctg.0000000000000269
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发表时间：
2020-12
影响因子：
3.6
通讯作者：
Mimori K
中科院分区：
文献类型：
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作者：
Kudo SE;Kouyama Y;Ogawa Y;Ichimasa K;Hamada T;Kato K;Kudo K;Masuda T;Otsu H;Misawa M;Mori Y;Kudo T;Hayashi T;Wakamura K;Miyachi H;Sawada N;Sato T;Shibata T;Hamatani S;Nemoto T;Ishida F;Niida A;Miyano S;Oshima M;Ogino S;Mimori K
与大多数由带蒂或无根突起腺瘤引起的结直肠癌不同，粘膜下浸润性（pT1）结直肠癌表现为表面凹陷（以下简称“凹陷性结直肠癌”，通过高清内窥镜识别）被认为源于凹陷的前体。我们假设凹陷型结直肠肿瘤具有不同于突出型和扁平型结直肠肿瘤的独特临床病理特征。我们将2001年至2017年间切除的27,129例结直肠肿瘤（909例pT1癌和26,220例腺瘤）分为凹陷型（211例癌和109例腺瘤）、扁平型（304例癌和11,246例腺瘤）和突出型（394例癌和14,865例腺瘤），并比较了它们的临床病理特征。作为pT1癌的探索性分析，我们对19个抑制和8个突出亚型进行了全外显子组测序，对8个抑制和8个突出亚型进行了RNA测序。pT1癌在凹陷性病变中（66%）比突出性病变（2.6%）和扁平性病变（2.6%）更常见（P < 0.001）。与非抑制性pT1癌相比，抑制性pT1癌与淋巴血管浸润、肿瘤出芽和大量粘膜下浸润呈正相关，与腺瘤成分的存在呈负相关（均P < 0.001）。抑制性腺瘤比非抑制性腺瘤更可能包含高级别不典型增生（49% vs 11%, P < 0.001）。KRAS突变仅在19例pT1抑制癌中的1例中观察到。与突出性癌相比，抑制性癌通常表现出更高的血管生成和上皮-间质转化相关基因的表达。抑制性结直肠肿瘤可能具有恶性组织病理表型和分子特征的独特组合。
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.