The Korean Journal of Internal Medicine Vol. 29, No. 5 (Suppl. 1)
WCIM 2014 SEOUL KOREA 509
Slide Session
K-GIO-03 GI Oncology
Pro-Oncogenic NM23 Contributes to
Hepatocarcinogenesis Through the AKT/ Extracellular Signal-Regulated Kinase (ERK)1/2 Pathway
Mi-Jin Lee1, Goung-Ran Yu1, Hua Lee1, Jun Zhang1, Yun-A Kim1, Dae-Ghon Kim1 Chonbuk National University Medical School and Hospital, Department of Internal Medicine, Division of GI and Hepatology, Korea1
Background: NM23 is a family of structurally and functionally conserved proteins known as nucleoside diphosphate kinases (NDPK). NM23-H1, NM23-H2 and NM23- LV are expressed abundantly in HCC. NM23-H2 is a basic protein recently identifi ed as the human PuF factor, which is a transcriptional activator of the c-Myc proto-onco- gene. Although the NM23 protein is implicated as a metastasis suppressor, the role of NM23 appears to be less understood. Thus, the aim of this study is to examine func- tional role and mechanism of NM23 involved tumorigenesis in HCC.
Methods: We examined the NM23-H1, H2 and LV mRNA expression in HCC by Real- time-PCR analysis and NM23-H1, H2 and LV protein expression in HCC by immunoblot and immunohistochemistry. Focus formation and anchorage-independent growth were examined in stable cell lines expressing NM23 using soft agar. Using overexpression of NM23 by adenoviral system, the molecular mechanism of NM23 mediated tumor cell growth was assessed in experimental cell culture and in vivo animal model.
Results: The level of NM23 expression in tumor tissues and the surrounding matrix appeared to be independent of etiology and tumor differentiation. Ectopic expression of NM23-H2 in NIH3T3 fi broblasts and HLK3 hepatocytes enhanced focus formation, and allowed anchorage-independent growth. Overexpression of NM23 results in in- creased tumor cell proliferation, which is relevant to activation of AKT and extracellu- lar signal-regulated kinase (ERK)1/2 phosphorylation. The NIH3T3 fi broblasts and HLK3 hepatocytes stably expressing NM23-H2 produced tumors in athymic mice. Lentiviral delivery of NM23-H2 shRNA inhibited tumor growth of xenotransplanted tumors pro- duced from HLK3 cells stably expressing NM23-H2.
Conclusions: These results indicate that NM23 may be pro-oncogenic and involved in hepatocarcinogenesis through AKT/ERK signaling pathway. Therefore, this pathway may be an useful target for HCC treatment.
K-GIO-04 GI Oncology
Expression of LIN28A and Clinicopathologic Characteristics in Gastric Cancers
Chan Hyuk Park1, Jung Hwa Lee1, Na Keum Lee1, Sang Kil Lee1
Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Institute of Gastroen- terology, Yonsei University College of Medicine, Korea1
Background: Although it has been known that LIN28A may play a role in the onco- genesis in various cancers, expression of LIN28A in gastric cancers has not been well evaluated. We investigated LIN28A expression in gastric cancer tissues and their adja- cent normal tissues and aimed to determine its clinicopathologic characteristics.
Methods: LIN28A expression between gastric cancers and adjacent normal tissues was evaluated by western blotting for 5 fresh gastric tissues and immunohistochem- istry (IHC) analysis on a tissue microarray (TMA), which constituted of 288 gastric cancer tissues and 288 adjacent normal tissues. The clinicopathological characteristics according to LIN28A expression was investigated by IHC analysis on a TMA.
Results: On western blotting, reduced expression of LIN28A in gastric cancer tissues was observed in 2 of 5 pairs of gastric tissues. On IHC analysis for a TMA, in addition, mean IHC score was signifi cantly lower in the gastric cancer tissues compared to the adjacent normal tissues (P < 0.001). However, there was no significant difference of clinicopathologic characteristics between stained and non-stained gastric cancer tissues. Overall survival also did not differ between stained and non-stained gastric cancer tissues.
Conclusions: Expression of LIN28A was reduced in the gastric cancer tissues com- pared to adjacent normal tissues. Clinicopathologic characteristics, however, did not differ in the gastric cancer tissues according to the LIN28A expression level.
K-GIO-05 GI Oncology
Prognostic Value of Metabolic Parameters from Preoperative
18F-FDG PET/CT in Patients with Stage III Gastric Cancer
Sae Jung Na1, Jae Myung Park2, Joo Hyun O1, Han Hee Lee2, Kyo Young Song3, Sung Hak Lee4, Sang-Young Roh2, Myung-Gyu Choi2, Cho Hyun Park3
Department of Radiology, The Catholic University of Korea, Korea1, Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Korea2, Department of Surgery, The Catholic University of Korea, Seoul St. Mary’s Hospital, Korea3, Department of Hospital Pathology, The Catholic University of Korea, Seoul St. Mary’s Hospital, Korea4
Background: This study assessed the prognostic value of metabolic parameters from preoperative 18F-FDG PET/CT in patients with curative surgical resection of stage III gastric cancer.
Methods: Patients who underwent staging preoperative 18F-FDG PET/CT and con- fi rmed to have stage III gastric cancer after curative surgical resection were retro- spectively enrolled. The maximum standardized uptake value (SUVmax) and peak SUV (SUVpeak) of the primary gastric cancer were measured from all patients. In addition, the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were computed in all cases showing perceptible FDG uptake. The prognostic values of the PET parameters and clinicopathologic factors for recurrence free survival (RFS) and overall survival (OS) were evaluated.
Results: 138 patients (male 89, female 49) were included, with age ranging from 26 to 83 years (mean±SD, 60.5±8.5). The TNM stage was IIIa in 41 patients, IIIb in 47 pa- tients and IIIc in 50 patients. Mean follow up duration was 41±18 month (range 0~65, median 46 months). On univariate analysis, the pathologic T stage (pT), pathologic N stage (pN), TNM stage, vein invasion, SUVmax and SUVpeak were signifi cant prognostic factors for RFS (pmax, SUVpeak, and TLG were signifi cant factors for OS (pmax were prog- nostic for RFS, while TNM stage and age were the prognostic factors for OS.
Conclusions: Higher SUVmax and SUVpeak of the primary tumor were associated with signifi cantly shorter RFS and OS. 18F-FDG PET/CT in patients with stage III gastric can- cer provides prognostic information prior to surgery.
K-GIO-06 GI Oncology
Assessment of Response to Preoperative Chemoradiotherapy for Rectal Cancer: Tumor Regression Grade vs. Pathologic Stage
In Ja PARK1, Chang Sik YU1, Chan Wook KIM1, Yong Sik YOON1, Seok-Byung LIM1, Jong Lyul LEE1, Jin Cheon KIM1
Asan Medical Center, Korea1
Background and Objectives: The aim of study is to compare the effectiveness of tu- mor regression grade (TR) with that of pathologic stage to assess the level of response to PCRT in terms of prediction of prognosis.
Methods : The patients with locally advanced (cT3-4 or cN+ by EUS or MRI) rectal carcinoma diagnosed from 2006 to 2009 and treated with PCRT and radical resection were identified from our colorectal database and records retrospectively reviewed.
Response to CRT was evaluated according to tumor regression grade (TRG; no, mini- mal, moderate, near total, and total regression) and pathologic stage. Recurrence-free survival (RFS) was compared among patients according to TRG and pathologic stage.
Results : Overall, 504 were identifi ed. Total regression represents pathologic stage 0 in 84.7%. No patients with moderate and minimal regression had p Stage 0. Except, total regression and p Stage 0, TRG was not correlated with pathologic stage. At a mean follow-up of 52 months, among patients with the same TRG category, the 3-year RFS rate differed signifi cantly according to the pathologic stage. By contrast, signifi cant differences were not found in 3-year RFS within pathologic stage according to TRG.
However, for pStage III patients, 3-year RFS was different according to TRG. In mul- tivariate analysis, pathologic stage showed stratifi ed association with RFS, but, TRG could not stratify prognostic group.
Conclusion: Pathologic stage was well associated with prognosis rather than TRG for patients without metastatic lymph node. However, patients with metastatic lymph node, 3-year RFS was different according to TRG. Among patients with rectal cancer received PCRT, tumor regression grade and pathologic stage could not predict progno- sis adequately as a single response assessment.
