Prognostic significance of metastasis-suppressor gene NM23 in gastric carcinoma
Keywords:Gastric carcinoma, Immunohistochemical staining, NM23
Aim: Metastasis is critical in the prognosis of gastric cancer patients and in deciding on treatment strategies. Therefore, studies have concentrated on metastasis suppressor genes. This study aimed to identify the characteristics of NM23 expression in gastric cancer and to investigate its anti-metastatic and prognostic significance.
Methods: Ninety patients who underwent surgery for gastric cancer between January 1, 2009 and January 1, 2010 were included in this study. Immunohistochemical staining was applied to specimen sections. The results of the immunohistochemical staining were evaluated with the normal gastric mucosa adjacent to the tumor. The degree of NM23 staining of tumor cell compared to the normal tissue was evaluated in two groups of “negative-weak staining” and “strong staining”. Both groups were analyzed for lymph node metastasis, vascular invasion, perineural invasion, degree of tumor differentiation, tumor stage and distant metastasis.
Results: Among 58 patients with lymph node metastasis, 70.7% showed negative-weak staining and 29.3% showed strong staining. Among 32 patients with no lymph node metastasis, 40.6% had negative-weak staining and 59.4% had strong staining. Decrease in NM23 expression was shown to cause an increase in lymph node metastasis (P=0.01). Furthermore, while there was no statistical significance, the rates of distant metastasis, degree of poor differentiation, tumors in stage III and stage IV were apparently higher in the negative-weak staining group. These results were in line with the anti-metastatic property of NM23.
Conclusion: This study showed that NM23 expression had anti-metastatic properties for lymph node metastasis in gastric cancer patients.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet TJ, Jemal A. Global cancer statistics 2012. CA Cancer J Clin. 2015 Mar;65(2):87–108.
Zhang M, Liu K, Wang F, Wen X, Song X. Association between CYP2E1 polymorphisms and risk of gastric cancer: an updated meta-analysis of 32 case-control studies. Mol Clin Oncol. 2016 Jun;4(6):1031–8.
Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: Descriptive epidemiology, risk factors, screening and prevention. Cancer Epidemiol Biomarkers Prev. 2014 May;23(5):700–13.
Radovic S, Doric M, Hukic A, Babic M, Kuskunovic S, Spahovic N. Immunohistochemical expression and significance of NM23 suppressor protein in primary gastric adenocarcinoma. Bosn J Basic Med Sci. 2013 May;13(2):72-7.
Steeg PS, Bevilacqua G, Kopper L, Thorgeirson UP, Talmadge JE, Liotta LA, et al. Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst. 1988 Apr;80(3):200–4.
MacDonald NJ, De La Rosa A, Steeg PS. The potential roles of nm23 in cancer metastasis and cellular differentiation. Eur J Cancer. 1995 Jul;31:1096-100.
Lin CH, Dammai V, Adryan B, Hsu T. Interaction between Nm23 and the tumor suppressor VHL. N S Arch Pharmacol. 2015 Feb;388(2):143-52.
Ajani JA. Gastroesophageal cancers: progress and problems. J Natl Compr Canc NE. 2008 Oct;6(9):813–4.
Boissan M, Dabernat S, Peuchant E, Schlattner U, Lascu I, Lacombe ML. The mammalian Nm23/NDPK family: from metastasis control to cilia movement. Mol Cell Biochem. 2009 Sep;329(1):51–62.
Barnes R, Masood S, Barker E, Rosengard AM, Coggin DL, Crowell T, et al. Low nm23/NDP kinase protein expression in infiltrating ductal breast carcinomas correlates with reduced patient survival. Am J Pathol. 1991;139:245–50.
Florenes VA, Aamdal S, Myklebost O, Maelandsmo GM, Bruland OS, Fodstad O. Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. Cancer Res. 1992 Nov;52(21):6088–91.
Nakayama T, Ohtsuru A, Nakao K, Shima M, Nakata K, Watanabe K, et al. Expression in human hepatocellular carcinoma of nucleoside diphosphate kinase, a homologue of the nm23 gene product. J Natl Cancer Inst. 1992 Sep;84:1349–54.
Ayhan A, Yasui W, Yolozaki H, Kitadai Y, Tahara E. Reduced expression of nm23 protein is associated with advanced tumor stage and distant metastases in human colorectal carcinomas. Virchows Arch B Cell Pathol. 1993 Dec;63:213–18.
Fang M, Tao Y, Liu Z, Huang H, Lao M, Huang L, Zhu B. Meta-analysis of the relationship between NM23 expression to gastric cancer risk and clinical features. Biomed Res Int. 2017;9:1-9. doi.org/10.1155/2017/8047183
Nakamori S, Ishikawa O, Ohhigashi H, Kameyama M, Furukawa H, Sasaki Y, et al. Expression of nucleoside diphosphate kinase/nm23 gene product in human pancreatic cancer: an association with lymph node metastasis and tumor invasion. Clin Exp Metastasis. 1993 Mar;11(2):151–8.
Wang CS, Lin KH, Hsu YC, Hsueh S. Distant metastasis of gastric cancer is associated with elevated expression of the antimetastatic Nm23 gene. Cancer Lett. 1998 Jun;128(1):23-9.
Dusonchet L, Corsale S, Migliavacca M, Calo V, Bazan V, Amato A, et al. Nm23-H1 expression does not predict clinical survival in colorectal cancer patients. Oncol Rep. 2003;10(5):1257-63.
Sarris M, Lee CS. Nm23 protein expression in colorectal carcinoma metastasis in regional lymph nodes and the liver. Euro J Surg Oncol. 2001 Mar;27(2):170-4.
Lee KE, Lee HJ, Kim YH, Yu HJ, Yang HK, Kim WH, et al. Prognostic Significance of p53, nm23, PCNA and c-erbB-2 in Gastric Cancer. Jpn J Clin Oncol. 2003 Apr;33(4):173-9.
Muller W, Schneiders A, Hommel G, Gabbert HE. Expression of Nm23 in gastric carcinoma: association with tumor progression and poor prognosis. Cancer 2000 Nov;83:2481-7.
Kodera Y, Isobe KI, Yamauchi M, Kondoh K, Kimura N, Akiyam S, et al. Expression of nm23 H-1 RNA levels in human gastric cancer tissues. A negative correlation with nodal metastasis. Cancer. 1994 Jan;73(2):259-65. doi.10.1002/1097-0142
Liu YJ, Yan PS, Li J, Jia FJ. Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer. World J Gastroenterol. 2005 Nov;11:6601-06.
Yu GZ, Wang JJ, Chen Y, Ni CR, Zhu MH. Expressions of nm23, P53 and S100A4 proteins and their relationships with metastasis potential in gastric carcinoma. Zhonghua Wei Chang Wai Ke Za Zhi. 2006 Mar;9(2):165-9.
Monig S, Nolden B, Lubke T, Pohl A, Grass G, Schneider PM, et al. Clinical significance of nm23 gene expression in gastric cancer. Anticancer Res. 2007 Jul;27(4):3029-33.
Yang T, Chen BZ, Li DF, Wang HM, Lin XS, Wei HF, et al. ReducedNM23 protein level correlates with worse clinicopathologic features in colorectal cancers: a meta-analysis of pooled data. Medicine. 2016 Jan;95:e2589. doi. 10.1097/MD.0000000000002589
How to Cite
Copyright (c) 2019 İsmail Biri, Yücel Gültekin, Suzan Bahadır, Kemal Deniz, Kadir Can Küçük
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.