Hereditary and sporadic papillary renal carcinomas with c-met mutations share a distinct morphological phenotype
Hereditary and sporadic papillary renal carcinomas with c-met mutations share a distinct morphological phenotype
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DOI：
10.1016/s0002-9440(10)65147-4
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发表时间：
1999-08-01
影响因子：
6
通讯作者：
Zbar, B
中科院分区：
文献类型：
--
作者：
Lubensky, IA;Schmidt, L;Zbar, B
在遗传性乳头状肾细胞癌患者中检测到c-met癌基因7q31的种系突变。此外，c-met突变在13%无肾肿瘤家族史的乳头状肾细胞癌患者中发挥作用。我们分析了来自6个生殖系c-met突变的遗传性乳头状肾细胞癌家族的29例患者的103例双侧乳头状肾细胞癌和4例转移的组织病理学，以及来自5名无直肠肿瘤家族史的6例c-met突变的乳头状肾细胞癌。25例散发性肾肿瘤具有突出的乳头状结构，没有体细胞c-met突变。所有c-met突变的乳头状肾细胞癌在结构上为75 - 100%乳头状/管状乳头状，并表现为嗜铬嗜碱性，乳头状肾细胞癌1型组织学。23例患者肿瘤中可见Fuhrman核1-2级，8例患者局部可见核3级。17例患者有多发乳头状腺瘤，肾实质周围可见显微镜下的乳头状病变。94%的乳头状肾细胞癌患者肿瘤中局灶性存在带胞浆内脂质和糖原的透明细胞。肾乳头状透明细胞。细胞癌具有小的嗜碱性核，透明的细胞区缺乏常规（透明）细胞肾细胞癌的细血管网络特征。我们认为，c-met突变的乳头状肾细胞癌患者可发生多发、双侧、乳头状的宏观和微观肾脏病变。c-met基因型肾肿瘤表现出独特的乳头状肾细胞癌1型表型，在遗传和组织学上不同于其他遗传性肾综合征和大多数散发的乳头状结构肾肿瘤。虽然所有具有c-met突变的遗传性和散发性乳头状肾细胞癌都具有1型乳头状肾细胞癌的组织学特征，但并非所有1型散发性乳头状肾细胞癌都具有c-met突变。
Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papillary renal cell carcinoma. In addition, c-met mutations were shown to play a role in 13% of patients with papillary renal cell carcinoma and no family history of renal tumors. The histopathology of papillary renal cell carcinoma with c-met mutations has not been previously described, We analyzed the histopathology of 103 bilateral archival papillary renal cell carcinomas and 4 metastases in 29 patients from 6 hereditary papillary renal cell carcinoma families with germline c-met mutations and 6 papillary renal cell carcinomas with c-met mutations from 5 patients with no family history of rectal tumors. Twenty-five sporadic renal tumors with prominent papillary architecture and without somatic c-met mutations were evaluated for comparison. All papillary renal cell carcinomas with c-met mutations were 75 to 100% papillary/tubulopapillary in architecture and showed chromophil basophilic, papillary renal cell carcinoma type 1 histology. Fuhrman nuclear grade 1-2 was seen in tumors from 23 patients, and nuclear grade 3 was observed focally in 8 patients. Seventeen patients had multiple papillary adenomas and microscopic papillary lesions in the surrounding renal parenchyma Clear cells with intracytoplasmic Lipid and glycogen were focally present in tumors of 94% papillary renal cell carcinoma patients. Clear cells of papillary renal. cell carcinoma had small basophilic nuclei, and clear cell areas lacked a fine vascular network characteristic of conventional (clear) cell renal cell carcinoma. We conclude that papillary renal cell carcinoma patients with c-met mutations develop multiple, bilateral, papillary macroscopic and microscopic renal lesions. Renal tumors with c-met genotype show a distinctive papillary renal cell carcinoma type 1 phenotype and are genetically and histologically different from renal tumors seen in other hereditary renal syndromes and most sporadic renal tumors with papillary architecture. Although all hereditary and sporadic papillary renal cell carcinomas with c-met mutations share papillary renal cell carcinoma type 1 histology, not all type 1 sporadic papillary renal cell carcinomas harbor c-met mutations.