琥珀酸脱氢酶缺陷型胃肠道间质瘤中琥珀酸脱氢酶各亚单位蛋白的表达情况

Expression of succinate dehydrogenase subunit protein in succinate dehydrogenase-deficient gastrointestinal stromal tumors

目的探讨琥珀酸脱氢酶（SDH）缺陷型胃肠道间质瘤（GIST）中琥珀酸脱氢酶复合体各亚单位蛋白的表达情况。方法收集贵州医科大学附属医院及四川大学华西医院病理科2003年1月至2017年1月期间经外科切除并经病理学检查证实的GIST标本352例．应用免疫组织化学EnVision二步法检测352例GIST肿瘤组织中琥珀酸脱氢酶各亚单位蛋白的表达情况，对阴性病例进行临床病理特征分析及随访，同时对阴性病例的CKIT基因第9、11、13及17号外显子及血小板源性生长因子受体仪（PDGFRA）基因第12和18号外显子进行扩增并检测。结果352例GIST中SDHB蛋白表达缺陷（阴性）15例，占4．3％（15／352），其中男性6例，女性9例；首诊年龄15～84岁（中位年龄53岁，平均年龄47岁）；肿瘤发生于胃14例、肠系膜1例；肿瘤直径0．5～15．0cm（平均6．9cm）；上皮样细胞型和混合细胞型各6例，梭形细胞型3例：其中8例在胃壁内呈多结节状生长。4例发生淋巴结转移，1例发生腹腔种植转移，1例发生肝脏、胰腺及淋巴结转移，1例发生脉管内浸润。在SDHB缺陷型GIST中，发现SDHA蛋白表达缺陷（阴性）2例（0．6％，2／352）；未发现SDHC及SDHD蛋白表达缺陷（阴性）病例。共5例获得随访，随访时间为7～151个月（平均56个月），其中1例于术后8个月死亡（死因不明）；4例无肿瘤转移和复发，患者本人及家族中均未发现副神经节瘤及肺软骨瘤等病史。15例SDH缺陷型GIST均未检测出CKIT及PDGFRA基因突变。结论SDH缺陷型GIST有独特的临床病理特征且预后较好，其中少数为SDHA缺陷。

Objective To investigate the expression of succinate dehydrogenase complex subunit protein in succinate dehydrogenase-deficient gastrointestinal stromal tumors （SDH-deficient GISTs ） . Methods Three hundred fifty-two cases of GISTs were collected from January 2003 to January 2017 at the Affiliated Hospital of Guizhou Medical University and West China Hospital of Sichuan University. The expression of succinate dehydrogenase subunit protein was detected by immunohistochemical EnVision technique in 352 cases of GISTs, and the negative cases were analyzed for clinicopathologic features and outcome. The gene segments of CKIT exons 9, 11, 13 and 17 and PDGFRA exons 12 and 18 were amplified and detected in SDH-deficient （negative） cases. Results A total of 15 SDHB-defieient （negative） GISTs （4. 3%, 15/352） were found among 352 cases of GISTs. Six patients were male and nine were female. The age of initial diagnosis ranged from 15 to 84 years （ median= 53 years ,mean = 47 years）. The tumor involved stomach （ 14 cases） and mesentery （ 1 case）. The tumor sizes varied from 0. 5 cm to 15.0 cm （ mean = 6. 9 cm）. There were six, six and three cases of epithelioid, mixed and spindle cell types respectively. Eight cases showed muhi-nodularity in the wall of stomach. Metastasis to lymph node was noted in four cases, one case showed intraperitoneal implantation metastasis. Metastases to liver, pancreas and lymph node were found in one case, and one case showed vascular invasion. Among SDHB-deficient GISTs, two SDHA- deficient （negative） cases were found （0. 6%, 2/352）, but there were no SDHC and SDHD deficient （negative） cases. Five of the fifieen SDH-deficient GISTs had follow-up data： one patient died 8 months after surgery from unknown cause, four had no recurrences or metastases, and there was no history of paraganglioma and pulmonary chondroma found in patients and their families. No mutation in CKIT and PDGFRA gene was identified in 15 cases of SDH-deficient GISTs. Conclusion SDH-deficient GISTs have unique clinicopathologic features and a favorable prognosis, and a small proportion of cases are SDHA- deficient.