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具有肠型表型且携带TP53 R175H突变的胃浸润性微乳头癌

Gastric Invasive Micropapillary Carcinoma with Intestinal Phenotypes Harboring a TP53 R175H Mutation.

作者信息

Ikeda Hideyuki, Kukitsu Takehiro, Johmen Wataru, Nakamura Hajime, Yamauchi Natumi, Ishikawa Kazuma, Saikawa Takashi, Noda Sayaka, Saitoh Tadanori, Ueno Yoshinori, Noda Yuuya, Yamazaki Sayuki, Kuroda Yoshikazu, Koshiko Susumu, Sasagawa Yutaka

机构信息

Divisions of Surgical Pathology, Rumoi City Hospital, Rumoi, Japan.

Divisions of Internal Medicine, Rumoi City Hospital, Rumoi, Japan.

出版信息

Case Rep Oncol. 2014 Sep 3;7(3):611-20. doi: 10.1159/000367583. eCollection 2014 Sep.

DOI:10.1159/000367583
PMID:25408652
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4209268/
Abstract

We report a case of gastric invasive micropapillary carcinoma (IMPC) in an 86-year-old female patient. She was admitted to our hospital with a chief complaint of bloody emesis. Upper gastrointestinal endoscopy found a gastric adenocarcinoma at the antrum. The biopsy specimens showed moderately differentiated adenocarcinoma with invasive small tumor nests. Distal gastrectomy with systematic lymph node dissection demonstrated that the tumor had IMPC through a pathological examination. Despite the depth of tumor invasion (the submucosa), extensive lymph node metastases were observed. Anti-D2-40 immunostaining revealed numerous infiltrating tumor cell nests in the lymphatic vessels, which could explain subsequent multiple lymph node metastases. The adenocarcinoma showed intestinal phenotypes by several immunohistochemical studies. One of these antibodies (CD10) clearly demonstrated the inverted apical-basal (inside-out) pattern of IMPC, whereas it showed an ordinary pattern in intestinal metaplasia adjacent to the tumor. Furthermore, genetic analysis by direct sequencing revealed a point mutation in the exon 5 of TP53 in the tumor. The mutation presumably harbors a missense mutation from Arg to His at the codon 175 (R175H). R175H has been previously described as a 'gain-of-function' mutation with a high invasive or metastatic potential in several types of cancers. In summary, this is one of the first reported cases of gastric IMPC with intestinal phenotypes harboring a TP53 R175H mutation in the literature.

摘要

我们报告一例86岁女性胃浸润性微乳头状癌(IMPC)患者。她因呕血为主诉入院。上消化道内镜检查发现胃窦部有胃腺癌。活检标本显示为中度分化腺癌,有浸润性小肿瘤巢。远端胃切除术加系统性淋巴结清扫术后病理检查显示肿瘤为IMPC。尽管肿瘤浸润深度为黏膜下层,但仍观察到广泛的淋巴结转移。抗D2-40免疫染色显示淋巴管内有大量浸润性肿瘤细胞巢,这可以解释随后的多处淋巴结转移。通过多项免疫组织化学研究,该腺癌显示出肠型表型。其中一种抗体(CD10)清楚地显示了IMPC的顶端-基底倒置(由内向外)模式,而在肿瘤邻近的肠化生中则显示出普通模式。此外,直接测序的基因分析显示肿瘤中TP53基因第5外显子存在一个点突变。该突变推测为密码子175处由精氨酸突变为组氨酸的错义突变(R175H)。R175H先前在几种癌症中被描述为具有高侵袭或转移潜能的“功能获得性”突变。总之,这是文献中首次报道的具有肠型表型且携带TP53 R175H突变的胃IMPC病例之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a2/4209268/1537f7c440e5/cro-0007-0611-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a2/4209268/d019a0dde622/cro-0007-0611-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a2/4209268/ad29700dae4f/cro-0007-0611-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a2/4209268/1537f7c440e5/cro-0007-0611-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a2/4209268/d019a0dde622/cro-0007-0611-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a2/4209268/ad29700dae4f/cro-0007-0611-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a2/4209268/1537f7c440e5/cro-0007-0611-g03.jpg

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本文引用的文献

1
Invasive micropapillary carcinoma: a distinct type of adenocarcinomas in the gastrointestinal tract.浸润性微乳头状癌:胃肠道腺癌的一种独特类型。
World J Gastroenterol. 2014 Apr 28;20(16):4597-606. doi: 10.3748/wjg.v20.i16.4597.
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A common p53 mutation (R175H) activates c-Met receptor tyrosine kinase to enhance tumor cell invasion.一种常见的p53突变(R175H)激活c-Met受体酪氨酸激酶以增强肿瘤细胞侵袭。
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Immunohistochemical analysis of invasive micropapillary carcinoma pattern in four cases of gastric cancer.
癌症体细胞突变的进展推断
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4例胃癌侵袭性微乳头癌模式的免疫组织化学分析
Med Mol Morphol. 2013 Jun;46(2):114-21. doi: 10.1007/s00795-013-0037-9. Epub 2013 Mar 9.
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Gastric carcinoma with invasive micropapillary pattern and its association with lymph node metastasis.胃浸润性微乳头状癌及其与淋巴结转移的关系。
Histopathology. 2011 Dec;59(6):1081-9. doi: 10.1111/j.1365-2559.2011.04055.x.
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Clinicopathological features of stomach cancer with invasive micropapillary component.具有浸润性微乳头状成分的胃癌的临床病理特征。
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Clinicopathological and molecular characterization of colorectal micropapillary carcinoma.结直肠微乳头状癌的临床病理及分子特征。
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Gastric micropapillary carcinoma: A distinct subtype with a significantly worse prognosis in TNM stages I and II.胃微乳头状癌:在 TNM Ⅰ期和Ⅱ期中具有明显更差预后的独特亚型。
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Micropapillary carcinoma of stomach: a clinicopathologic and immunohistochemical study of 11 cases.胃微乳头状癌:11 例临床病理及免疫组化研究。
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Elevated expression of p53 gain-of-function mutation R175H in endometrial cancer cells can increase the invasive phenotypes by activation of the EGFR/PI3K/AKT pathway.子宫内膜癌细胞中 p53 功能获得性突变 R175H 的高表达可通过激活 EGFR/PI3K/AKT 通路增加侵袭表型。
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DN-R175H p53 mutation is more effective than p53 interference in inducing epithelial disorganization and activation of proliferation signals in human carcinoma cells: role of E-cadherin.DN-R175H p53突变在诱导人癌细胞上皮组织紊乱和增殖信号激活方面比p53干扰更有效:E-钙黏蛋白的作用
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