Oncogenic BRAF and KRAS mutations in endosalpingiosis.
Oncogenic BRAF and KRAS mutations in endosalpingiosis.
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DOI：
10.1002/path.5353
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发表时间：
2020-02
期刊：
影响因子：
--
通讯作者：
Shih IM
中科院分区：
文献类型：
--
作者：
Chui MH;Shih IM
输卵管内肿大是一种由输卵管上皮异位组成的显微病变，常累及卵巢浆液性交界性肿瘤或低级别浆液性癌患者的腹膜和淋巴结，但其致病意义尚不清楚。利用激光捕获显微解剖和液滴数字PCR，我们研究了输卵管内膜增生是否包含卵巢低级别浆液性肿瘤特征的BRAF和KRAS驱动突变。在分析的43例输卵管内病变中，有14例（33%）检测到体细胞突变。在21例伴有卵巢同步或异时性低级别浆液性肿瘤的输卵管内肿大患者中，有11例（52%）女性在输卵管内肿大病变中发现了突变，其中大多数病例（10/11,91%）在肿瘤和输卵管内肿大中都发现了相同的突变。相反，在13例与卵巢肿瘤无关的输卵管内腔病中，只有1例携带KRAS突变。Ki-67免疫组化评价的增殖活性在输卵管内病变中低于低级别浆液性肿瘤，而BRAF或KRAS突变的输卵管内病变的Ki-67指数明显低于未突变的输卵管内病变。KRASG12V在输卵管上皮细胞中的异位表达导致ERK磷酸化、p21诱导、生长停滞和细胞衰老。总之，我们证明输卵管内肿大是看似正常的细胞中癌症驱动突变的一个有趣例子，在绕过内源性肿瘤抑制机制后，这些细胞可能容易发生肿瘤转化。
Endosalpingiosis, a microscopic lesion composed of ectopic Fallopian tube epithelium, frequently involves the peritoneum and lymph nodes in patients with ovarian serous borderline tumour or low-grade serous carcinoma, but its pathogenic significance remains unclear. Using laser-capture microdissection and droplet digital PCR, we investigated whether endosalpingiosis harbours the driver mutations in BRAF and KRAS that characterise ovarian low-grade serous neoplasms. Somatic mutations were detected in 14 (33%) of 43 endosalpingiotic lesions analysed. Of 21 women with endosalpingiosis associated with a synchronous or metachronous ovarian low-grade serous tumour, mutations were identified in endosalpingiotic lesions from 11 (52%) women, with most cases (10/11, 91%) demonstrating identical mutations in both tumour and endosalpingiosis. In contrast, of 13 cases of endosalpingiosis not associated with an ovarian tumour, only one harboured a KRAS mutation. The proliferative activity as assessed by Ki-67 immunohistochemistry was lower in endosalpingiosis than in low-grade serous tumours, and endosalpingiosis with either a BRAF or KRAS mutation had a significantly lower Ki-67 index than those without. Ectopic expression of KRASG12V in Fallopian tube epithelial cells led to ERK phosphorylation, p21 induction, growth arrest and cellular senescence. In conclusion, we demonstrate that endosalpingiosis represents an interesting example of cancer driver mutations in deceptively normal-appearing cells, which may be prone to neoplastic transformation upon bypass of endogenous oncosuppressive mechanisms.
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DOI：
10.1097/pas.0000000000000313
发表时间：
2014-12
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Zeppernick F;Ardighieri L;Hannibal CG;Vang R;Junge J;Kjaer SK;Zhang R;Kurman RJ;Shih IeM
通讯作者：
Shih IeM
DOI：
10.1056/nejmoa1614814
发表时间：
2017-05-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Anglesio MS;Papadopoulos N;Ayhan A;Nazeran TM;Noë M;Horlings HM;Lum A;Jones S;Senz J;Seckin T;Ho J;Wu RC;Lac V;Ogawa H;Tessier-Cloutier B;Alhassan R;Wang A;Wang Y;Cohen JD;Wong F;Hasanovic A;Orr N;Zhang M;Popoli M;McMahon W;Wood LD;Mattox A;Allaire C;Segars J;Williams C;Tomasetti C;Boyd N;Kinzler KW;Gilks CB;Diaz L;Wang TL;Vogelstein B;Yong PJ;Huntsman DG;Shih IM
通讯作者：
Shih IM
影响因子：
5.6
作者：
Djordjevic, Bojana;Clement-Kruzel, Stacia;Malpica, Anais
通讯作者：
Malpica, Anais
影响因子：
6.4
作者：
Turashvili G;Grisham RN;Chiang S;DeLair DF;Park KJ;Soslow RA;Murali R
通讯作者：
Murali R
影响因子：
7.3
作者：
Ardighieri, Laura;Zeppernick, Felix;Hannibal, Charlotte G.;Vang, Russell;Cope, Leslie;Junge, Jette;Kjaer, Susanne K.;Kurman, Robert J.;Shih, Ie-Ming
通讯作者：
Shih, Ie-Ming