title: Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma.
abstract: The present study aimed to investigate anaplastic lymphoma kinase (ALK) status in hepatocellular carcinoma (HCC) and to evaluate whether abnormalities in expression were associated with patient prognosis.ALKstatus was investigated using immunohistochemistry (IHC), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescencein situhybridization (FISH) assays in 342 HCC patients. In addition, rapid amplification of complementary DNA ends-coupled PCR sequencing was performed, in order to confirm the presence ofALKabnormalities in patients exhibitingALKmessenger RNA (mRNA) overexpression. The correlation betweenALKexpression and the clinicopathological features and prognosis of the HCC patients was statistically analyzed. The results of the present study revealed overexpression of ALK protein and mRNA; furthermore,ALKgene copy number gains were observed via IHC (44.7%; 153/342), RT-qPCR (47.4%; 162/342) and FISH (32.7%; 112/342) analyses, althoughALKrearrangement or mutation was not demonstrated in the results of any of these assays. ALK protein expression levels were significantly associated with hepatitis C virus (HCV) status (P<0.001) and the presence of micrometastases (P=0.011). Within the entire patient cohort,ALKexpression was associated with poor progression-free survival (PFS; P=0.041). Subsequent analysis in patient subgroups that demonstrated hepatitis B surface antigen positivity, HCV negativity, stage III-IV disease, recurrence and micrometastasis positivity revealed that overall survival (OS) and PFS were significantly reduced in those patients exhibitingALKexpression compared with those patients who were negative forALKexpression. Multivariate analysis revealed thatALKexpression was an independent risk factor for OS (P=0.042) and PFS (P=0.033), particularly for patients with stage III-IV tumors. Thus,ALKmay serve as a novel indicator for the metastatic behavior and prognosis of HCC.
authors: Department of Oncology, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors: Jianhua
authors: J
authors: Liu
authors: Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors: Haosheng
authors: H
authors: Jin
authors: Medical Research Center, Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors: Hongxia
authors: H
authors: Tian
authors: Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Guoda
authors: G
authors: Lian
authors: Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Shaojie
authors: S
authors: Chen
authors: Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Jiayu
authors: J
authors: Li
authors: Medical Research Center, Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors: Xuchao
authors: X
authors: Zhang
authors: Department of Oncology, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors: Dong
authors: D
authors: Ma
keywords: anaplastic lymphoma kinase; clinicopathological characteristics; hepatocellular carcinoma; micrometastases; prognosis