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具有印戒细胞成分的结直肠癌和具有黏液成分的结直肠癌的独特分子特征。

Distinct molecular features of colorectal carcinoma with signet ring cell component and colorectal carcinoma with mucinous component.

作者信息

Ogino Shuji, Brahmandam Mohan, Cantor Mami, Namgyal Chungdak, Kawasaki Takako, Kirkner Gregory, Meyerhardt Jeffrey A, Loda Massimo, Fuchs Charles S

机构信息

Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.

出版信息

Mod Pathol. 2006 Jan;19(1):59-68. doi: 10.1038/modpathol.3800482.

Abstract

Signet ring cell carcinoma and mucinous carcinoma are distinct subtypes of colorectal adenocarcinoma. The morphologic and molecular spectra of colorectal carcinomas with various signet ring cell components and colorectal carcinomas with various mucinous components, compared to non-mucinous adenocarcinomas, have not been examined. The study groups consisted of 39 carcinomas with various signet ring cell components ('the signet group'), 167 carcinomas with various mucinous components ('the mucinous group'), and 457 nonmucinous adenocarcinoma. We visually estimated the amounts of signet ring cell and mucinous components in tumors, and subclassified the signet and mucinous groups according to the amount of each component (< or = 19, 20-49, and > or = 50%). We sequenced BRAF and KRAS, analyzed for microsatellite instability (MSI) and 18q loss of heterozygosity (LOH), and performed immunohistochemistry for TP53, cyclooxygenase-2 (COX2), MLH1, O-6-methylguanine DNA methyltransferase (MGMT), p16 (CDKN2A), and fatty acid synthase (FASN). Signet ring cell carcinoma (> or = 50% signet ring cell tumors) and < or = 49% signet ring cell tumors showed similar molecular features. Except for MSI and MGMT, > or = 50% mucinous tumors and < or = 49% mucinous tumors also showed similar molecular features. BRAF mutations, MSI, and MLH1 loss were more frequent in both the signet and mucinous groups than nonmucinous carcinoma. More frequent KRAS mutations and less frequent p16 loss and TP53 positivity were observed in the mucinous group than nonmucinous carcinoma. 18q LOH and COX2 overexpression were less common in the signet group than nonmucinous carcinoma. FASN levels were highest in the mucinous group, followed by nonmucinous carcinoma, and lowest in the signet group. In conclusion, a minor (< or = 49%) signet ring cell or mucinous component in colorectal carcinoma suggests molecular features similar to > or = 50% signet ring cell or mucinous carcinoma, respectively. Signet ring cell carcinoma and mucinous carcinoma are related subtypes of colorectal adenocarcinoma, but have molecular features distinct from each other.

摘要

印戒细胞癌和黏液腺癌是结直肠癌的不同亚型。与非黏液腺癌相比,具有不同印戒细胞成分的结直肠癌以及具有不同黏液成分的结直肠癌的形态学和分子特征尚未得到研究。研究组包括39例具有不同印戒细胞成分的癌(“印戒组”)、167例具有不同黏液成分的癌(“黏液组”)和457例非黏液腺癌。我们通过视觉评估肿瘤中印戒细胞和黏液成分的数量,并根据每种成分的数量(≤19%、20%-49%和≥50%)对印戒组和黏液组进行亚分类。我们对BRAF和KRAS进行测序,分析微卫星不稳定性(MSI)和18号染色体杂合性缺失(LOH),并对TP53、环氧合酶-2(COX2)、MLH1、O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)、p16(CDKN2A)和脂肪酸合酶(FASN)进行免疫组化检测。印戒细胞癌(≥50%印戒细胞肿瘤)和≤49%印戒细胞肿瘤表现出相似的分子特征。除MSI和MGMT外,≥50%黏液肿瘤和≤49%黏液肿瘤也表现出相似的分子特征。BRAF突变、MSI和MLH1缺失在印戒组和黏液组中比非黏液腺癌更常见。与非黏液腺癌相比,黏液组中KRAS突变更频繁,p16缺失和TP53阳性更少见。18q LOH和COX2过表达在印戒组中比非黏液腺癌更少见。FASN水平在黏液组中最高,其次是非黏液腺癌,在印戒组中最低。总之,结直肠癌中少量(≤49%)的印戒细胞或黏液成分分别提示与≥50%印戒细胞或黏液癌相似的分子特征。印戒细胞癌和黏液腺癌是结直肠癌的相关亚型,但具有彼此不同的分子特征。

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