PMID- 26475437 OWN - NLM STAT- MEDLINE DCOM- 20160629 LR - 20181113 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 15 DP - 2015 Oct 16 TI - Clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma. PG - 721 LID - 10.1186/s12885-015-1737-4 [doi] LID - 721 AB - BACKGROUND: More knowledge about genetic and molecular features of cholangiocarcinoma is needed to develop effective therapeutic strategies. We investigated the clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma. METHODS: One hundred ninety-four patients with curatively resected intrahepatic cholangiocarcinoma were included in this study. Tumor tissue specimens were collected and analyzed for ROS1 gene rearrangement using fluorescence in situ hybridization (FISH) and ROS1 protein expression using immunohistochemistry (IHC). RESULTS: ROS1 immunohistochemistry was positive (moderate or strong staining) in 72 tumors (37.1 %). ROS1 protein expression was significantly correlated with well differentiated tumors, papillary or mucinous histology, oncocytic/hepatoid or intestinal type tumors, and periductal infiltrating or intraductal growing tumors (vs. mass-forming cholangiocarcinoma). ROS-expressing tumors were associated with better disease-free survival (30.1 months for ROS1 expression (+) tumors vs. 9.0 months for ROS1 (-) tumors, p = 0.006). Moreover, ROS1 expression was an independent predictor of better disease-free survival in a multivariate analysis (HR 0.607, 95 % CI 0.377-0.976; p = 0.039). Although break-apart FISH was successfully performed in 102 samples, a split pattern indicative of ROS1 gene rearrangement was not found in the examined samples. CONCLUSION: ROS1 protein expression was associated with well-differentiated histology and better survival in our patients with resected intrahepatic cholangiocarcinoma. ROS1 gene rearrangement by break-apart FISH was not found in the examined samples. FAU - Lee, Kyung-Hun AU - Lee KH AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. kyunghunlee@snu.ac.kr. AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. kyunghunlee@snu.ac.kr. FAU - Lee, Kyoung-Bun AU - Lee KB AD - Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. kblee@snuh.org. FAU - Kim, Tae-Yong AU - Kim TY AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. ktyongmd@gmail.com. AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. ktyongmd@gmail.com. FAU - Han, Sae-Won AU - Han SW AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. saewonhan@gmail.com. AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. saewonhan@gmail.com. FAU - Oh, Do-Youn AU - Oh DY AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. ohdoyoun@snu.ac.kr. AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. ohdoyoun@snu.ac.kr. FAU - Im, Seock-Ah AU - Im SA AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. moisa@snu.ac.kr. AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. moisa@snu.ac.kr. FAU - Kim, Tae-You AU - Kim TY AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. kimty@snu.ac.kr. AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. kimty@snu.ac.kr. FAU - Yi, Nam-Joon AU - Yi NJ AD - Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea. gsleenj@hanmail.net. FAU - Lee, Kwang-Woong AU - Lee KW AD - Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea. kwleegs@gmail.com. FAU - Suh, Kyung-Suk AU - Suh KS AD - Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea. kssuh@snu.ac.kr. FAU - Jang, Ja-June AU - Jang JJ AD - Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. tripj@snu.ac.kr. FAU - Bang, Yung-Jue AU - Bang YJ AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. bangyj@snu.ac.kr. AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. bangyj@snu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151016 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (ROS1 protein, human) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cholangiocarcinoma/*genetics/pathology/surgery MH - Disease-Free Survival MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Liver/*metabolism/pathology/surgery MH - Male MH - Middle Aged MH - *Prognosis MH - Protein-Tyrosine Kinases/*biosynthesis/genetics MH - Proto-Oncogene Proteins/*biosynthesis/genetics MH - Tissue Array Analysis PMC - PMC4609147 EDAT- 2015/10/18 06:00 MHDA- 2016/06/30 06:00 PMCR- 2015/10/16 CRDT- 2015/10/18 06:00 PHST- 2015/05/01 00:00 [received] PHST- 2015/10/08 00:00 [accepted] PHST- 2015/10/18 06:00 [entrez] PHST- 2015/10/18 06:00 [pubmed] PHST- 2016/06/30 06:00 [medline] PHST- 2015/10/16 00:00 [pmc-release] AID - 10.1186/s12885-015-1737-4 [pii] AID - 1737 [pii] AID - 10.1186/s12885-015-1737-4 [doi] PST - epublish SO - BMC Cancer. 2015 Oct 16;15:721. doi: 10.1186/s12885-015-1737-4.