Zheng Song, Chen Li-Rong, Wang Hai-Jun, Chen Shui-Zhen
Department of Oncology, Hangzhou First People's Hospital of Zhejiang Province, Hangzhou, China.
Hepatogastroenterology. 2007 Dec;54(80):2285-90.
BACKGROUND/AIMS: To investigate the effect of the expression and mutation of c-kit and PDGFR-alpha gene and its association with clinical pathology and prognosis of gastrointestinal stromal tumor (GIST).
Paraffin-embedded tissues from 119 GISTs were analyzed for CD 117 and PDGFR-alpha expression by immunohistochemical method. Fifty GISTs were measured for the presence of c-kit exons 9, 11 and 13 mutations and PDGFR-alpha exons 12, 18 mutations.
Of 119 GISTs, 104 (87.4%) were positive for CD-117, 65.5% (78/119) were positive for PDGFR-alpha. Positive signals were located mainly on cell membrane and cytoplasma. Overall, c-kit mutations were detected in 42% of GIST patients which were all exon 11 mutations. The types of c-kit exon 11 mutations were heterogeneous and clustered between Codon 556-560, the classic "hot spot" at the 5'end of exon 11. PDGFR-alpha mutations were identified in 20% of all the 50 cases while four of the positive cases did not express detectable CD117. The commonest type of mutation was the point mutation of D842V of exon 18. Mutations of exon 12 were found in 2 GISTs.
As a sensitive and specific marker of GIST, PDGFR-alpha can be used in GIST combined with CD117, especially in the diagnosis and differential diagnosis of GIST that does not express CD-117. c-kit oncogenic mutations have no obvious relationship with biological behavior of GIST. PDGFR-alpha oncogenic mutations are more likely seen in giant, CD-117-negative GISTs arising outside the gastrointestinal tract and have an unfavorable clinical course. C-kit oncogenic mutations are more likely seen in CD-117-positive GISTs arising in the gastrointestinal tract and have no obvious relationship with biological behavior of GISTs. The majority of PDGFR-alpha-mutated GISTs were of epithelioid or mixed cell type while the majority of kit-mutated GISTs were of spindle cell type.
背景/目的：探讨c-kit和血小板衍生生长因子受体α（PDGFR-α）基因的表达与突变及其与胃肠道间质瘤（GIST）临床病理及预后的关系。
采用免疫组化法分析119例GIST石蜡包埋组织中CD117和PDGFR-α的表达情况。对50例GIST检测c-kit基因第9、11和13外显子以及PDGFR-α基因第12、18外显子的突变情况。
119例GIST中，104例（87.4%）CD-117阳性，78例（65.5%）PDGFR-α阳性。阳性信号主要位于细胞膜和细胞质。总体而言，42%的GIST患者检测到c-kit突变，均为第11外显子突变。c-kit第11外显子突变类型具有异质性，集中在密码子556-560之间，即第11外显子5'端的经典“热点”区域。50例患者中20%检测到PDGFR-α突变，其中4例阳性病例未检测到可检测的CD117表达。最常见的突变类型是第18外显子的D842V点突变。2例GIST检测到第12外显子突变。
作为GIST敏感且特异的标志物，PDGFR-α可与CD117联合用于GIST诊断，尤其适用于不表达CD-117的GIST的诊断与鉴别诊断。c-kit致癌突变与GIST的生物学行为无明显关系。PDGFR-α致癌突变更常见于胃肠道外发生的巨大、CD-117阴性GIST，且临床病程不良。c-kit致癌突变更常见于胃肠道发生的CD-117阳性GIST，与GIST的生物学行为无明显关系。大多数PDGFR-α突变的GIST为上皮样或混合细胞型，而大多数c-kit突变的GIST为梭形细胞型。
