PMID- 26870191 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 11 IP - 1 DP - 2016 Jan TI - Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma. PG - 213-223 AB - 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. ALK status was investigated using immunohistochemistry (IHC), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (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 of ALK abnormalities in patients exhibiting ALK messenger RNA (mRNA) overexpression. The correlation between ALK expression 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, ALK gene copy number gains were observed via IHC (44.7%; 153/342), RT-qPCR (47.4%; 162/342) and FISH (32.7%; 112/342) analyses, although ALK rearrangement 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, ALK expression 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 exhibiting ALK expression compared with those patients who were negative for ALK expression. Multivariate analysis revealed that ALK expression was an independent risk factor for OS (P=0.042) and PFS (P=0.033), particularly for patients with stage III-IV tumors. Thus, ALK may serve as a novel indicator for the metastatic behavior and prognosis of HCC. FAU - Liu, Jianhua AU - Liu J AD - Department of Oncology, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China. FAU - Jin, Haosheng AU - Jin H AD - Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China. FAU - Tian, Hongxia AU - Tian H AD - Medical Research Center, Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China. FAU - Lian, Guoda AU - Lian G AD - Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China. FAU - Chen, Shaojie AU - Chen S AD - Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China. FAU - Li, Jiayu AU - Li J AD - Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China. FAU - Zhang, Xuchao AU - Zhang X AD - Medical Research Center, Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China. FAU - Ma, Dong AU - Ma D AD - Department of Oncology, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China. LA - eng PT - Journal Article DEP - 20151104 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC4727030 OTO - NOTNLM OT - anaplastic lymphoma kinase OT - clinicopathological characteristics OT - hepatocellular carcinoma OT - micrometastases OT - prognosis EDAT- 2016/02/13 06:00 MHDA- 2016/02/13 06:01 PMCR- 2015/11/04 CRDT- 2016/02/13 06:00 PHST- 2014/11/12 00:00 [received] PHST- 2015/09/24 00:00 [accepted] PHST- 2016/02/13 06:00 [entrez] PHST- 2016/02/13 06:00 [pubmed] PHST- 2016/02/13 06:01 [medline] PHST- 2015/11/04 00:00 [pmc-release] AID - OL-0-0-3859 [pii] AID - 10.3892/ol.2015.3859 [doi] PST - ppublish SO - Oncol Lett. 2016 Jan;11(1):213-223. doi: 10.3892/ol.2015.3859. Epub 2015 Nov 4.