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Tumor Biology

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05.01.2016 | Original Article

Predictable factors for lymph node metastasis in early gastric cancer analysis of clinicopathologic factors and biological markers

verfasst von: Yi-Wei Wang, Mei-Ling Zhu, Rui-Fen Wang, Wen-Ji Xue, Xue-Ru Zhu, Li-Feng Wang, Lei-Zhen Zheng

Erschienen in: Tumor Biology | Ausgabe 7/2016

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Abstract

Predicting lymph node metastasis (LNM) accurately is very important to decide treatment strategies preoperatively. The aim of this study was to explore risk factors that predict the presence of LNM in early gastric cancer (EGC). A total of 230 patients with EGC who underwent curative gastrectomy with lymph adenectomy at Xinhua Hospital from January 2006 to July 2014 were retrospectively reviewed. We studied the relationship between clinicopathological factors, biological markers (p53, ki67, nm23, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), E-cadherin (E-cad), beta-catenin (b-catenin), glutathione S-transferase (GST), and topoisomerase II (Topo II)), and LNM of EGC patients by chi-square test and logistic regression analysis. Meta-analyses were further conducted to review the effects of the proteins (P53, ki67, E-cad, and b-catenin) on LNM in ECG patients. LNM was detected in 42 (18.3 %) of 230 patients. Incidences of LNM was distinct in different tumor size (p = 0.044), depth of submucosal invasion (p < 0.0001), and P53 overexpression (p = 0.004). Multivariate analysis further indentified that large tumor size (≥20 mm, odds ratio (OR) = 2.168, p = 0.041), submucosa (OR = 4.000, p = 0.0005), and P53 overexpression (OR = 3.010, p = 0.022) were independent risk factors of LNM in EGC patients. The meta-analysis revealed a significantly statistical association of P53, ki67, and b-catenin with an increased risk of LNM in EGC patients (P53, OR = 1.81, p = 0.017; ki67, OR = 2.53, p = 0.0003; b-catenin, OR = 0.53, p = 0.01). Tumor size (≥20 mm), the depth of invasion (submucosa), and P53 overexpression may be helpful predictors of LNM in EGC patients. Furthermore, the results of meta-analysis revealed that P53, ki67 overexpression, and abnormal expression of b-catenin may be associated with LNM in EGC. The results need further validation in single large studies.

Kajitani T. The general rules for the gastric cancer study in surgery and pathology. Part I. Clinical classification. Jpn J Surg. 1981;11:127–39.CrossRefPubMed

Wu CY, Chen JT, Chen GH, Yeh HZ. Lymph node metastasis in early gastric cancer: a clinicopathological analysis. Hepatogastroenterology. 2002;49:1465–8.PubMed

Mouri R, Yoshida S, Tanaka S, Oka S, Yoshihara M, Chayama K. Usefulness of endoscopic ultrasonography in determining the depth of invasion and indication for endoscopic treatment of early gastric cancer. J Clin Gastroenterol. 2009;43:318–22.CrossRefPubMed

Boku T, Nakane Y, Okusa T, Hirozane N, Imabayashi N, Hioki K, et al. Strategy for lymphadenectomy of gastric cancer. Surgery. 1989;105:585–92.PubMed

Popiela T, Kulig J, Kolodziejczyk P, Sierzega M. Long-term results of surgery for early gastric cancer. Br J Surg. 2002;89:1035–42.CrossRefPubMed

Seto Y, Shimoyama S, Kitayama J, Mafune K, Kaminishi M, Aikou T, et al. Lymph node metastasis and preoperative diagnosis of depth of invasion in early gastric cancer. Gastric Cancer. 2001;4:34–8.CrossRefPubMed

Ren G, Cai R, Zhang WJ, Ou JM, Jin YN, Li WH. Prediction of risk factors for lymph node metastasis in early gastric cancer. World J Gastroenterol. 2013;19:3096–107.CrossRefPubMedPubMedCentral

Noh SH, Hyung WJ, Cheong JH. Minimally invasive treatment for gastric cancer: approaches and selection process. J Surg Oncol. 2005;90:188–94.CrossRefPubMed

Shin N, Jeon TY, Kim GH, Park DY. Unveiling lymph node metastasis in early gastric cancer. World J Gastroenterol. 2014;20:5389–95.CrossRefPubMedPubMedCentral

10.

Ono H, Kondo H, Gotoda T, Shirao K, Yamaguchi H, Saito D, et al. Endoscopic mucosal resection for treatment of early gastric cancer. Gut. 2001;48:225–9.CrossRefPubMedPubMedCentral

11.

Gotoda T, Yamamoto H, Soetikno RM. Endoscopic submucosal dissection of early gastric cancer. J Gastroenterol. 2006;41:929–42.CrossRefPubMed

12.

Fenoglio-Preiser CM, Wang J, Stemmermann GN, Noffsinger A. TP53 and gastric carcinoma: a review. Hum Mutat. 2003;21:258–70.CrossRefPubMed

13.

Xiangming C, Hokita S, Natsugoe S, Tanabe G, Baba M, Takao S, et al. Cooccurrence of reduced expression of alpha-catenin and overexpression of p53 is a predictor of lymph node metastasis in early gastric cancer. Oncology-Basel. 1999;57:131–7.CrossRef

14.

Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984;133:1710–5.PubMed

15.

Weigel MT, Dowsett M. Current and emerging biomarkers in breast cancer: prognosis and prediction. Endocr Relat Cancer. 2010;17:R245–62.CrossRefPubMed

16.

Backer JM, Mendola CE, Kovesdi I, Fairhurst JL, O’Hara B, Eddy RJ, et al. Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2. Oncogene. 1993;8:497–502.PubMed

17.

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;13:72–7.PubMedPubMedCentral

18.

Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta LA, et al. Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst. 1988;80:200–4.CrossRefPubMed

19.

Lieto E, Ferraraccio F, Orditura M, Castellano P, Mura AL, Pinto M, et al. Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients. Ann Surg Oncol. 2008;15:69–79.CrossRefPubMed

20.

Jin EH, Lee DH, Jung SA, Shim KN, Seo JY, Kim N, et al. Clinicopathologic factors and molecular markers related to lymph node metastasis in early gastric cancer. World J Gastroenterol. 2015;21:571–7.CrossRefPubMedPubMedCentral

21.

Ozawa M, Baribault H, Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 1989;8:1711–7.PubMedPubMedCentral

22.

Ozawa M, Ringwald M, Kemler R. Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proc Natl Acad Sci U S A. 1990;87:4246–50.CrossRefPubMedPubMedCentral

23.

Ozawa M, Kemler R. Molecular organization of the uvomorulin-catenin complex. J Cell Biol. 1992;116:989–96.CrossRefPubMed

24.

Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, et al. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991;113:173–85.CrossRefPubMed

25.

Vleminckx K, Vakaet LJ, Mareel M, Fiers W, van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991;66:107–19.CrossRefPubMed

26.

Geng M, Wang L, Chen X, Cao R, Li P. The association between chemosensitivity and Pgp. GST-pi and Topo II expression in gastric cancer. Diagn Pathol. 2013;8:198.CrossRefPubMedPubMedCentral

27.

Japanese GCA. Japanese classification of gastric carcinoma - 2nd English edition -. Gastric Cancer. 1998;1:10–24.CrossRef

28.

Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer. 2011;14:113–23.

29.

Hu B, El HN, Sittler S, Lammert N, Barnes R, Meloni-Ehrig A. Gastric cancer: classification, histology and application of molecular pathology. J Gastrointest Oncol. 2012;3:251–61.PubMedPubMedCentral

30.

Tanaka M, Kitajima Y, Edakuni G, Sato S, Miyazaki K. Abnormal expression of E-cadherin and beta-catenin may be a molecular marker of submucosal invasion and lymph node metastasis in early gastric cancer. Br J Surg. 2002;89:236–44.PubMed

31.

Nagatsuma AK, Aizawa M, Kuwata T, Doi T, Ohtsu A, Fujii H, et al. Expression profiles of HER2, EGFR, MET and FGFR2 in a large cohort of patients with gastric adenocarcinoma. Gastric Cancer. 2015;18:227–38.CrossRefPubMed

32.

DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMed

33.

MANTEL N, HAENSZEL W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMed

34.

Egger M, Davey SG, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.CrossRefPubMedPubMedCentral

35.

Maehara Y, Orita H, Okuyama T, Moriguchi S, Tsujitani S, Korenaga D, et al. Predictors of lymph node metastasis in early gastric cancer. Br J Surg. 1992;79:245–7.CrossRefPubMed

36.

Gotoda T. Endoscopic resection of early gastric cancer. Gastric Cancer. 2007;10:1–11.CrossRefPubMed

37.

Tong JH, Sun Z, Wang ZN, Zhao YH, Huang BJ, Li K, et al. Early gastric cancer with signet-ring cell histologic type: risk factors of lymph node metastasis and indications of endoscopic surgery. Surgery. 2011;149:356–63.CrossRefPubMed

38.

Lim MS, Lee HW, Im H, Kim BS, Lee MY, Jeon JY, et al. Predictable factors for lymph node metastasis in early gastric cancer-analysis of single institutional experience. J Gastrointest Surg. 2011;15:1783–8.CrossRefPubMed

39.

Guadagni S, Reed PI, Johnston BJ, De Bernardinis G, Catarci M, Valenti M, et al. Early gastric cancer: follow-up after gastrectomy in 159 patients. Br J Surg. 1993;80:325–8.CrossRefPubMed

40.

Adachi Y, Yasuda K, Inomata M, Shiraishi N, Kitano S, Sugimachi K. Clinicopathologic study of early-stage mucinous gastric carcinoma. Cancer. 2001;91:698–703.CrossRefPubMed

41.

Ohashi S, Okamura S, Urano F, Maeda M. Clinicopathological variables associated with lymph node metastasis in submucosal invasive gastric cancer. Gastric Cancer. 2007;10:241–50.CrossRefPubMed

42.

Kwee RM, Kwee TC. Predicting lymph node status in early gastric cancer. Gastric Cancer. 2008;11:134–48.CrossRefPubMed

43.

Carson DA, Lois A. Cancer progression and p53. Lancet. 1995;346:1009–11.CrossRefPubMed

44.

Chang F, Syrjanen S, Syrjanen K. Implications of the p53 tumor-suppressor gene in clinical oncology. J Clin Oncol. 1995;13:1009–22.CrossRefPubMed

45.

Zheng Y, Wang L, Zhang JP, Yang JY, Zhao ZM, Zhang XY. Expression of p53, c-erbB-2 and Ki67 in intestinal metaplasia and gastric carcinoma. World J Gastroenterol. 2010;16:339–44.CrossRefPubMedPubMedCentral

46.

Sasaki O, Kido K, Nagahama S. DNA ploidy, Ki-67 and p53 as indicators of lymph node metastasis in early gastric carcinoma. Anal Quant Cytol Histol. 1999;21:85–8.PubMed

47.

Kanai T, Konno H, Maruyama K, Baba M, Tanaka T, Maruo Y, et al. P53 overexpression and proliferative activity do not correlate with lymph node metastasis in early gastric cancer. Eur Surg Res. 1997;29:35–41.CrossRefPubMed

48.

Jiaqing L, Hokita S, Xiangming C, Natsugoe S, Tanabe G, Baba M, et al. Role of cyclin E and p53 expression in progression of early gastric cancer. Gastric Cancer. 1998;1:160–5.CrossRefPubMed

49.

Goncalves AR, Carneiro AJ, Martins I, de Faria PA, Ferreira MA, de Mello EL, et al. Prognostic significance of p53 protein expression in early gastric cancer. Pathol Oncol Res. 2011;17:349–55.CrossRefPubMed

50.

Goishi H, Tanaka S, Haruma K, Yoshihara M, Sumii K, Kajiyama G, et al. Predictive value of Cathepsin D and Ki-67 expression at the deepest penetration site for lymph node metastases in gastric cancer. Oncol Rep. 2000;7:713–8.PubMed

51.

Cai J, Ikeguchi M, Tsujitani S, Maeta M, Liu J, Kaibara N. Significant correlation between micrometastasis in the lymph nodes and reduced expression of E-cadherin in early gastric cancer. Gastric Cancer. 2001;4:66–74.CrossRefPubMed

52.

Yoshii T, Miyagi Y, Nakamura Y, Kobayashi O, Kameda Y, Ohkawa S. Pilot research for the correlation between the expression pattern of E-cadherin-beta-catenin complex and lymph node metastasis in early gastric cancer. Tumori. 2013;99:234–8.PubMed

53.

Blok P, Craanen ME, Dekker W, Tytgat GN. Loss of E-cadherin expression in early gastric cancer. Histopathology. 1999;34:410–5.CrossRefPubMed

54.

Shun CT, Wu MS, Lin MT, Chang MC, Lin JT, Chuang SM. Immunohistochemical evaluation of cadherin and catenin expression in early gastric carcinomas: correlation with clinicopathologic characteristics and helicobacter pylori infection. Oncology-Basel. 2001;60:339–45.CrossRef

55.

Yi KD, Kyoon JJ, Kyu PY, Yeob RS, Soo KH, Kyun NB, et al. E-cadherin expression in early gastric carcinoma and correlation with lymph node metastasis. J Surg Oncol. 2007;96:429–35.CrossRef

56.

Joo YE, Rew JS, Choi SK, Bom HS, Park CS, Kim SJ. Expression of e-cadherin and catenins in early gastric cancer. J Clin Gastroenterol. 2002;35:35–42.CrossRefPubMed

57.

Xiangming C, Hokita S, Nuruki K, Toyoyama H, Tanabe G, Baba M, et al. The expression of cadherin-catenin complex in association with the clinicopathologic features of early gastric cancer. Surg Today. 1998;28:587–94.CrossRefPubMed

58.

Chen C, Yang JM, Hu TT, Xu TJ, Yan G, Hu SL, et al. Prognostic role of human epidermal growth factor receptor in gastric cancer: a systematic review and meta-analysis. Arch Med Res. 2013;44:380–9.CrossRefPubMed

59.

Galizia G, Lieto E, Orditura M, Castellano P, Mura AL, Imperatore V, et al. Epidermal growth factor receptor (EGFR) expression is associated with a worse prognosis in gastric cancer patients undergoing curative surgery. World J Surg. 2007;31:1458–68.CrossRefPubMed

Titel: Predictable factors for lymph node metastasis in early gastric cancer analysis of clinicopathologic factors and biological markers
verfasst von: Yi-Wei Wang
Mei-Ling Zhu
Rui-Fen Wang
Wen-Ji Xue
Xue-Ru Zhu
Li-Feng Wang
Lei-Zhen Zheng
Publikationsdatum: 05.01.2016
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 7/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4721-3

Springer Medizin

Predictable factors for lymph node metastasis in early gastric cancer analysis of clinicopathologic factors and biological markers

Abstract

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