Clinicopathological and molecular features of hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinomas
Clinicopathological and molecular features of hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinomas
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DOI：
10.1136/jclinpath-2020-206548
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发表时间：
2020-12-01
影响因子：
3.4
通讯作者：
Yao, Masahiro
中科院分区：
文献类型：
--
作者：
Furuya, Mitsuko;Iribe, Yasuhiro;Yao, Masahiro
遗传性平滑肌瘤病和肾细胞癌（HLRCC）是一种由富马酸水合酶（FH）基因突变引起的常染色体显性遗传病。受影响的家庭患肾细胞癌（RCC）的风险增加。HLRCC-RCC（HLRCC-RCC）具有高度侵袭性。基因诊断的HLRCC-RCC患者的临床病理信息有助于建立有效的theraps.MethodsTen日本HLRCC-RCC患者参加了这项研究。对FH进行了基因检测。在13个肿瘤中研究了FH的体细胞突变和FH和B7家族配体（PD-L1和B7-H3）的免疫组织化学分析。在两个tumors.ResultsAll患者FH种系突变的拷贝数变异进行了评估。关于组织学，大多数肿瘤具有2型乳头状结构或管状囊性结构或两者兼而有之。免疫组化显示所有肿瘤均为FH缺陷。10个肿瘤对PD-L1呈阳性，12个肿瘤对B7-H3呈阳性。体细胞突变分析表明FH杂合性丢失在10个肿瘤。拷贝数变异分析显示，单亲二体性之间的1q24.2和1 q44包括FH，染色体2 p的增益也很常见。所有患者都有转移或残留肿瘤。三名患者死于HLRCC-RCC和结肠癌之一，而其他六个目前还活着，包括两个没有recurrence. ConclusionsHLRCC-RCC似乎有独特的分子特征，包括PD-L1表达。1例患者对免疫治疗完全应答，这可能是HLRCC-RCC的一种选择。
AimsHereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder caused by germline mutations in fumarate hydratase (FH). Affected families have an increased risk of renal cell carcinoma (RCC). HLRCC-associated RCC (HLRCC-RCC) is highly aggressive. Clinicopathological information of genetically diagnosed patients with HLRCC-RCC contributes to the establishment of effective therapies.MethodsTen Japanese patients with HLRCC-RCC were enrolled in the study. Genetic testing for FH was carried out. Somatic mutations in FH and immunohistochemical analyses of FH and B7 family ligands (PD-L1 and B7-H3) were investigated in 13 tumours. Copy number variations were evaluated in two tumours.ResultsAll patients had FH germline mutations. Regarding histology, most tumours had type 2 papillary architecture or tubulocystic pattern or both. All tumours were FH deficient by immunohistochemistry. Ten tumours were positive for PD-L1, and 12 tumours were positive for B7-H3. Somatic mutation analysis demonstrated loss of heterozygosity of FH in 10 tumours. Copy number variation analysis revealed uniparental disomy between 1q24.2 and 1q44 encompassing FH; gain of chromosome 2 p was also common. All patients had either metastases or residual tumours. Three patients died of HLRCC-RCC and one of colon cancer, whereas the other six are currently alive, including two without recurrence.ConclusionsHLRCC-RCCs appear to have unique molecular profiles, including PD-L1 expression. One patient had complete response to immunotherapy, which may be an option for HLRCC-RCC.