Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers
Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers
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DOI：
10.1111/cge.13014
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发表时间：
2017-12-01
影响因子：
3.5
通讯作者：
Benusiglio, P. R.
中科院分区：
文献类型：
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作者：
Muller, M.;Ferlicot, S.;Benusiglio, P. R.
我们通过探索所有法国病例（代表迄今为止最大的系列）来解决有关遗传性平滑肌瘤病和肾细胞癌（HLRCC）的不确定性。通过桑格测序和 qPCR/MLPA 进行富马酸水合酶 (FH) 种系测试。必要时测量酶活性。我们尽可能对 RCC 和 S-(2-琥珀酰)-半胱氨酸 (2SC)/富马酸水合酶免疫组织化学进行病理学检查。我们使用非参数 Kaplan-Meier 估计生存率。共有114个家庭的182例。 34 名携带者（19%）中诊断出 37 例 RCC，中位年龄为 40 岁。在 23 例进行病理学检查的 RCC 中，13 例为乳头状 2 型。其中 4 例乳头状 RCC 类型未明确，3 例未分类，2 例管状囊性，1 例集合管（CD）RCC，全部为 2SC+，大多数（8/10）FH-。其余 14 例报告了 2 型乳头状、未特指乳头状、CD 和透明细胞组织学。绝大多数肾细胞癌 (82%) 在诊断时已发生转移或迅速发生转移。转移性疾病的中位生存期为 18 个月 (95% CI: 11-29)。 133例（73%）有皮肤平滑肌瘤病史，其中3例发展为皮肤平滑肌肉瘤。子宫肌瘤在女性中常见（77%），但未观察到肉瘤。只有 2 例患有嗜铬细胞瘤/副神经节瘤。结论我们的研究结果对于 HLRCC 患者的识别和治疗具有直接影响。
We addressed uncertainties regarding hereditary leiomyomatosis and renal cell carcinoma (HLRCC) by exploring all French cases, representing the largest series to date. Fumarate hydratase (FH) germline testing was performed with Sanger sequencing and qPCR/MLPA. Enzyme activity was measured when necessary. We carried out whenever possible a pathology review of RCC and S-(2-succino)-cysteine (2SC)/fumarate hydratase immunohistochemistry. We estimated survival using non-parametric Kaplan-Meier. There were 182 cases from 114 families. Thirty-seven RCC were diagnosed in 34 carriers (19%) at a median age of 40. Among the 23 RCC with pathology review, 13 were papillary type 2. There were 4 papillary RCC of unspecified type, 3 unclassified, 2 tubulocystic, and 1 collecting duct (CD) RCC, all 2SC+ and most (8/10) FH-. Of the remaining 14, papillary type 2, papillary unspecified, CD, and clear cell histologies were reported. The vast majority of RCC (82%) were metastatic at diagnosis or rapidly became metastatic. Median survival for metastatic disease was 18months (95%CI: 11-29). 133 cases (73%) had a history of cutaneous leiomyomas, 3 developed skin leiomyosarcoma. Uterine leiomyomas were frequent in women (77%), but no sarcomas were observed. Only 2 cases had pheochromocytomas/paraganglioma.ConclusionOur findings have direct implications regarding the identification and management of HLRCC patients.