Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants.
Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants.
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DOI：
10.1002/path.4293
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发表时间：
2014-01
影响因子：
7.3
通讯作者：
Shih, Ie-Ming
中科院分区：
文献类型：
--
作者：
Ardighieri, Laura;Zeppernick, Felix;Hannibal, Charlotte G.;Vang, Russell;Cope, Leslie;Junge, Jette;Kjaer, Susanne K.;Kurman, Robert J.;Shih, Ie-Ming
关于卵巢浆液性交界性肿瘤/非典型增生性浆液性肿瘤（SBT/APST）相关的腹膜植入物是否来源于原发性卵巢肿瘤或在腹膜中独立出现存在争议。我们分析了来自丹麦全国肿瘤登记处的45例晚期疾病患者的57例SBT/APST。KRAS和BRAF热点突变分析在55例APST中获得成功，并在34例（61.8%）和8例（14.5%）中证实了KRAS突变。突变分析在56例腹膜植入物中获得成功，并在34例（60.7%）中发现KRAS突变，在7例（12.5%）中发现BRAF突变。在两个原发性肿瘤和九个植入物中无法进行突变分析，这要么是因为DNA扩增失败，要么是因为没有足够的组织进行突变分析。对于这些标本，我们进行了VE 1免疫组织化学染色，结果表明它是V600 E BRAF突变的特异性且敏感的替代标记物。VE 1染色在2个APST中的1个和9个种植体中的7个中呈阳性。因此，在已知突变状态的63个植入物中，（通过直接突变分析或通过VE 1免疫组织化学），34（53.9%）有KRAS突变，14例（22%）有BRAF突变，其中在37个SBT/APST-植入物对中的34个（91%）中发现了相同的KRAS突变，在14个SBT/APST-植入物对中的14个（100%）中发现了相同的BRAF突变。植入物对。野生型KRAS和BRAF（在研究的基因座）在11/11（100%）SBT/APST-植入物对中发现。在62对SBT/APST-植入物（非侵入性和侵入性）中，59对的KRAS和BRAF突变的总体一致性为95%（p < 0.00001）。这项研究提供了令人信服的证据表明，绝大多数腹膜植入物，非侵入性和侵入性，具有与相关SBT/APST中存在的相同的KRAS或BRAF突变，支持腹膜植入物来源于原发性卵巢肿瘤的观点。
There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced-stage disease identified from a nation-wide tumour registry in Denmark. Mutational analysis for hotspots in KRAS and BRAF was successful in 55 APSTs and demonstrated KRAS mutations in 34 (61.8%) and BRAF mutations in eight (14.5%). Mutational analysis was successful in 56 peritoneal implants and revealed KRAS mutations in 34 (60.7%) and BRAF mutations in seven (12.5%). Mutational analysis could not be performed in two primary tumours and in nine implants, either because DNA amplification failed or because there was insufficient tissue for mutational analysis. For these specimens we performed VE1 immunohistochemistry, which was shown to be a specific and sensitive surrogate marker for a V600E BRAF mutation. VE1 staining was positive in one of two APSTs and seven of nine implants. Thus, among 63 implants for which mutation status was known (either by direct mutational analysis or by VE1 immunohistochemistry), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST–implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST–implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11 SBT/APST–implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST–implant (non-invasive and invasive) pairs (p < 0.00001). This study provides cogent evidence that the vast majority of peritoneal implants, non-invasive and invasive, harbour the identical KRAS or BRAF mutations that are present in the associated SBT/APST, supporting the view that peritoneal implants are derived from the primary ovarian tumour.
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DOI：
10.1097/pgp.0b013e3180336287
发表时间：
2007-10-01
影响因子：
2.4
作者：
Emerson, Robert E.;Wang, Mingsheng;Cheng, Liang
通讯作者：
Cheng, Liang
影响因子：
3.3
作者：
Li, MM;Cannizzaro, LA
通讯作者：
Cannizzaro, LA
DOI：
10.1111/igc.0b013e3181a83119
发表时间：
2009-12-01
影响因子：
4.8
作者：
Verbruggen, Marjolijn B.;Sieben, Nathalie L. G.;Dorsman, Josephine C.
通讯作者：
Dorsman, Josephine C.
影响因子：
11.2
作者：
Tang, XN;Shigematsu, H;Wistuba, II
通讯作者：
Wistuba, II
影响因子：
4.7
作者：
Boyd J;Luo B;Peri S;Wirchansky B;Hughes L;Forsythe C;Wu H
通讯作者：
Wu H