BRAF V600E突变型胃肠间质瘤13例临床病理及预后分析

BRAF V600E mutant gastrointestinal stromal tumors:a clinicopathological and prognostic analysis of thirteen cases

目的探讨BRAF V600E突变型胃肠间质瘤(gastrointestinal stromal tumor,GIST)的临床病理学特征及预后。方法收集13例BRAF V600E免疫组化阳性GIST,采用ARMS法和Sanger测序进行验证。回顾性分析13例BRAF V600E突变型GIST的临床病理学特征及随访,并采用2008版NIH方案和良恶性分析方法进行生存分析。结果13例BRAF V600E突变型GIST中男性5例,女性8例。年龄范围41~69岁,平均54.8岁。发病部位:胃5例、十二指肠3例、小肠4例、大网膜1例。肿瘤最大径0.9~25 cm,平均5.3 cm。手术切除标本8例,内镜切除标本5例。梭形细胞型11例,上皮样细胞型2例。NIH危险度分级:极低危5例、低危3例、中危0例、高危5例;中山方法:非恶性5例(良性3例,交界性2例)、低度恶性5例、中度恶性2例、高度恶性1例。随访时间2~84个月,平均32个月,11例无瘤生存,2例术后用伊马替尼分别治疗6个月和15个月后肿瘤进展。NIH高危患者疾病进展率为40%;中山方法的中度恶性疾病进展率为50%,高度恶性疾病进展率为100%。结论BRAF V600E突变型GIST罕见,可发生于消化道多个部位,细胞形态以梭形细胞型为主,偶见上皮样细胞型,免疫组化标记BRAF V600E可用于BRAF V600E突变型GIST的初筛,具有广谱的生物学行为,伊马替尼治疗无明确疗效。

Purpose To analyze the clinicopathological features and biological behavior of BRAF V600E mutant gastrointestinal stromal tumors(GISTs).Methods Thirteen cases of GISTs with immunohistochemical staining of BRAF V600E were collected.BRAF V600E mutation status was detected by ARMS method in these cases and then verified by Sanger sequencing.Clinicopathological features and follow-up of these cases were retrospectively analyzed.Moreover,the 2008 version of NIH scheme and benign and malignant analysis method were used for survival analysis.Results There were 5 males and 8 females in 13 cases of BRAF V600E mutant GIST.The age range was 41 to 69 years,with an average of 54.8 years.Five GISTs located in stomach,3 in duodenum,4 in small intestine,and 1 in omentum.The diameter of tumors ranged from 0.9 to 25 cm,with an average of 5.3 cm.Surgical resection was performed in 8 cases and endoscopic resection in 5 cases.Of all the 13 cases,11 were diagnosed as spindle type and 2 epithelioid type.According to NIH criteria,patients in very low,low and high risk groups were 5,3 and 5 cases,respectively.Patients in nonmalignant group were 5(3 cases of benign and 2 of borderline)and 8 cases(including 5 cases of low-grade malignancy,2 of moderate and 1 of high malignancy)were in malignant group based on“Zhongshan”method.The mean follow-up time was 32 months(range 2-84 months).Eleven patients survived with tumor-free,and 2 patients had tumor progression after 6 and 15 months of imatinib treatment.The disease progression rate was 40%in high-risk group(NIH criteria),50%and 100%in moderate and high malignancy group(Zhongshan method),respectively.Conclusion BRAF V600E mutant GIST is extremely rare and can occur in multiple parts of the digestive tract.The cell morphology is mainly spindle cell type,and the epithelioid cell type is occasionally seen.BRAF V600E immunohistochemistry can be used for primary screening.This kind of GIST harbors a diversity of biological behavior,and a few cases show malignant biological behavior.There is no definite efficacy of imatinib therapy.