Abstract:Objective: To investigate the protein expression of eight molecules including DNA topoisomerase 2α (TOP2A) in gastric cancer patients with lymphovascular invasion. Methods: A retrospective study was conducted in 242 patients with gastric adenocarcinoma. The protein expressions of TOP2A, tubulin β3, thymidylate synthase(TS), nonmetastatic protein 23(NM23), Pglycoprotein, proliferation marker Ki67,excision repair crosscomplementation group 1(ERCC1) and human epidermal growth factor receptor 2(HER2) in paraffinembedded tumor tissues were detected by immunohistochemistry and were compared between patients with and without lymphovascular invasion. Results: Lymphovascular invasion was detected in 81 patients (33.5%), and the proportions of female patients, patients with the longest diameter of tumor≥5 cm, nerve invasion and TNM stages of Ⅲ-Ⅳ were significantly higher in these patients than that in patients without lymphovascular invasion(P<0.05). The high expression rate of TOP2A protein in patients with lymphovascular invasion(89.3%) was significantly higher than that in those without lymphovascular invasion(72.9%,P<0.05), and this difference was mainly found in subgroups of female(100% vs 72.2%,P=0.045) and histological grade of Ⅲ (89.3% vs 67.6%,P=0.040). The high expression rates of tubulin β3, TS, NM23, Pglycoprotein, Ki67, ERCC1 and HER2 protein were not significantly different between these two groups(P>0.05). Conclusion: Gastric cancer patients with lymphovascular invasion had a significantly higher expression rate of TOP2A protein compared with those without lymphovascular invasion, suggesting the role of TOP2A in lymphovascular invasion.
戴东方, 陈德玉, 李小琴, 顾汉刚, 王德强. 胃癌组织DNA拓扑异构酶2α等8种分子的蛋白表达与脉管侵犯的关系[J]. 江苏大学学报:医学版, 2018, 28(02): 149-153.
DAI Dong-fang, CHEN De-yu, LI Xiao-qin, GU Han-gang, WANG De-qiang. Relationship between protein expression of eight molecules including DNA topoisomerase 2α and lymphovascular invasion in gastric cancer patients. Journal of Jiangsu University(Medicine Edition), 2018, 28(02): 149-153.
[1]Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015\[J\]. CA Cancer J Clin, 2016, 66(2):115-132.[2]Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012\[J\] .CA Cancer J Clin,2015,65(2):87-108.[3]Ajani JA, D′Amico TA, Almhanna K, et al. Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology\[J\]. J Natl Compr Canc Netw, 2016, 14(10):1286-1312.[4]Zhao LY, Chen XL, Wang YG, et al. A new predictive model combined of tumor size, lymph nodes count and lymphovascular invasion for survival prognosis in patients with lymph nodenegative gastric cancer\[J\]. Oncotarget, 2016,7(44):72300-72310.[5]Li P, He HQ, Zhu CM, et al. The prognostic significance of lymphovascular invasion in patients with resectable gastric cancer: a large retrospective study from Southern China\[J\]. BMC Cancer, 2015,15:370.[6]Lee JH, Kim MG, Jung MS, et al. Prognostic significance of lymphovascular invasion in nodenegative gastric cancer\[J\]. World J Surg, 2015,39(3):732-739.[7]Mete O, Asa SL. Pathological definition and clinical significance of vascular invasion in thyroid carcinomas of follicular epithelial derivation\[J\]. Mod Pathol, 2011,24(12):1545-1552.[8]Bartley AN, Washington MK, Colasacco C, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: Guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology\[J\]. J Clin Oncol,2017,35(4):446-464.[9]Li JC, Yang XR, Sun HX, et al. Upregulation of Kr ppellike factor 8 promotes tumor invasion and indicates poor prognosis for hepatocellular carcinoma\[J\]. Gastroenterology, 2010,139(6):2146-2157.[10]del Casar JM, Corte MD, Alvarez A, et al. Lymphatic and/or blood vessel invasion in gastric cancer: relationship with clinicopathological parameters, biological factors and prognostic significance\[J\]. J Cancer Res Clin Oncol, 2008,134(2):153-161.[11]Kim JH, Park SS, Park SH, et al. Clinical significance of immunohistochemicallyidentified lymphatic and/or blood vessel tumor invasion in gastric cancer\[J\]. J Surg Res, 2010,162(2):177-183.[12]Zhang S, Zhang D, Gong M, et al. High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer\[J\].BMC Cancer,2017,17(1):335.[13]Yuan H, Dong Q, Zheng B, et al. Lymphovascular invasion is a high risk factor for stage Ⅰ/Ⅱ colorectal cancer: a systematic review and metaanalysis\[J\].Oncotarget,2017,8(28): 46565-46579.[14]Kinoshita T, Ohtsuka T, Yotsukura M, et al. Prognostic impact of preoperative tumor marker levels and lymphovascular invasion in pathological stage Ⅰ adenocarcinoma and squamous cell carcinoma of the lung\[J\]. J Thorac Oncol, 2015,10(4):619-628.[15]Gresta LT, RodriguesJunior IA, de Castro LP, et al. Assessment of vascular invasion in gastric cancer: a comparative study\[J\]. World J Gastroenterol, 2013,19(24):3761-3769.[16]Du CY, Chen JG, Zhou Y, et al. Impact of lymphatic and/or blood vessel invasion in stage Ⅱ gastric cancer\[J\]. World J Gastroenterol, 2012,18(27):3610-3616.[17]Baxter J, Sen N, Martínez VL, et al. Positive supercoiling of mitotic DNA drives decatenation by topoisomerase Ⅱ in eukaryotes\[J\]. Science, 2011, 331(6022):1328-1332.[18]Li X, Dong W, Qu X, et al. Molecular dysexpression in gastric cancer revealed by integrated analysis of transcriptome data\[J\]. Oncol Lett,2017,13(5):3177-3185.[19]Wang Y. Transcriptional regulatory network analysis for gastric cancer based on mRNA microarray\[J\]. Pathol Oncol Res,2017, 23(4):785-791.[20]Terashima M, Ichikawa W, Ochiai A, et al. TOP2A, GGH, and PECAM1 are associated with hematogenous, lymph node, and peritoneal recurrence in stage Ⅱ/Ⅲ gastric cancer patients enrolled in the ACTSGC study\[J\]. Oncotarget, 2017, 8(34):57574-57582.[21]Ejlertsen B, Tuxen MK, Jakobsen EH, et al. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2Anormal breast cancer: DBCG 07READ, an openlabel, phase Ⅲ, randomized trial\[J\]. J Clin Oncol, 2017,35(23):2639-2646.[22]Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer\[J\]. N Engl J Med,2006,355(1):11-20.[23]Sumpter K, HarperWynne C, Cunningham D, et al. Report of two protocol planned interim analyses in a randomised multicentre phase Ⅲ study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF\[J\]. Br J Cancer, 2005,92(11):1976-1983.[24]Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer\[J\]. N Engl J Med,2008,358(1):36-46.