Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
Histopathology. 2017 Jul;71(1):53-62. doi: 10.1111/his.13185. Epub 2017 Apr 18.
Anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC) is a rare subtype of RCC reported in recent years, with eight cases so far. The aims of the present study were to screen ALK-rearranged cases from a large cohort of RCCs in China to determine the frequency of ALK rearrangement and investigate the clinicopathological features and outcomes.
Tissues from a total of 477 RCC patients in China were embedded into tissue microarrays for immunostaining. Fluorescence in-situ hybridization (FISH) and fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR) were applied to identify and confirm the rearrangement of ALK, and to identify the genes fused with ALK. ALK expression was identified in two of 477 RCCs. By FISH analysis, the two tumours showed either a 1R1G1F or a 2R2G signal pattern, indicating rearrangement involving ALK. Fluorescence quantitative RT-PCR detected the TPM3-ALK fusion and EML4-ALK fusion transcripts in the two tumours, respectively. Follow-up data were analyzed for the two cases and eight other ALK-rearranged RCCs reported in the literature. Two patients died from RCCs, on the 16th month and 48th month after surgery, respectively. The 5-year cancer-specific survival rate of patients with the 10 ALK-rearranged RCCs was lower than that of patients with International Society of Urological Pathology (ISUP) G1, G2 and G3 clear cell RCC (CCRCC) and papillary RCC (PRCC), but higher than that of patients with G4 CCRCC and PRCC.
ALK-rearranged RCC is a rare subtype of adult RCC and is associated with distinct histological features and a poor prognosis. Identification of ALK-rearranged RCC has important clinical significance, because patients might benefit from ALK inhibitor therapy as used in lung adenocarcinoma.
间变性淋巴瘤激酶（ALK）重排肾细胞癌（RCC）是近年来报道的一种罕见的 RCC 亚型，迄今为止已有 8 例。本研究的目的是从中国的一个大型 RCC 队列中筛选出 ALK 重排病例，以确定 ALK 重排的频率，并研究其临床病理特征和结局。
对来自中国的 477 例 RCC 患者的组织进行了组织微阵列免疫染色。应用荧光原位杂交（FISH）和荧光定量逆转录聚合酶链反应（RT-PCR）来鉴定和确认 ALK 的重排，并鉴定与 ALK 融合的基因。在 477 例 RCC 中，有 2 例显示 ALK 表达。通过 FISH 分析，这两个肿瘤显示出 1R1G1F 或 2R2G 信号模式，表明 ALK 涉及重排。荧光定量 RT-PCR 分别在这两个肿瘤中检测到 TPM3-ALK 融合和 EML4-ALK 融合转录本。对这两个病例和文献中报道的另外 8 例 ALK 重排 RCC 的随访数据进行了分析。2 例患者分别在手术后的第 16 个月和第 48 个月死于 RCC。10 例 ALK 重排 RCC 患者的 5 年癌症特异性生存率低于国际泌尿病理学会（ISUP）G1、G2 和 G3 透明细胞 RCC（CCRCC）和乳头状 RCC（PRCC）患者，但高于 G4 CCRCC 和 PRCC 患者。
ALK 重排 RCC 是一种罕见的成人 RCC 亚型，具有独特的组织学特征和不良预后。鉴定 ALK 重排 RCC 具有重要的临床意义，因为患者可能受益于在肺腺癌中使用的 ALK 抑制剂治疗。
