CDX2 Expression in Gastric Carcinoma: A Clinicopathological Study

Abstract

Background: Gastric cancer accounts for 7.8% of cancers worldwide and adenocarcinoma is the commonest histological type. Both gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas. CDX2 is an intestinal transcription factor, which can be demonstrated in intestinal metaplasia and gastric carcinomas of the intestinal type. Unlike colorectal carcinomas, the role of CDX2 in gastric carcinomas as a prognostic variable is yet to be established. Ki-67 is a transcription factor expressed in the growth and synthetic phases of the cell cycle. Aims and Objectives: The aims of the study were to analyze CDX2 expression and Ki-67 labeling index in different histological types of gastric carcinomas and their relationship with the patients' clinicopathological parameters. Materials and Methods: A total of 50 gastric carcinoma cases were evaluated histologically and phenotypically, along with assessment of CDX2 expression and Ki-67 labeling index. Gastric carcinomas were grouped into intestinal and diffuse types, according to Lauren classification. A semiquantitative microscopic evaluation of CDX2 expression and Ki-67 labeling index was performed and correlated with the patients' clinicopathological parameters. Results: Increased CDX2 expression correlated with higher proportion of intestinal type gastric carcinomas and a lower proportion of lymph node metastasis, lymphovascular and perineural invasion. On the other hand, high Ki-67 labeling index was found in high grade tumors with lymphovascular invasion. Conclusions: The results of our study suggest that CDX2 might be a useful marker in predicting the prognosis of patients with gastric carcinoma. Accordingly, Ki-67 index seems to be useful in identifying a group of patients with aggressive tumors.

Keywords

Adenocarcinoma - CDX2 - gastric carcinoma - Ki-67

Publication History

Article published online:
23 June 2021

• References

• 1 Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO Classification of Tumors of the Digestive System. Lyon: IARC 2010; 4: 48-58
• 2 Parkin DM. International variation. Oncogene 2014; 23: 6329-34
• 3 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-917
• 4 Lauren P, Sarin YK. The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 1965; 64: 31-49
• 5 Suh E, Chen L, Taylor J, Traber PG. A homeodomain protein related to caudal regulates intestine-specific gene transcription. Mol Cell Biol 1994; 14: 7340-51
• 6 Mizoshita T, Inada K, Tsukamoto T, Kodera Y, Yamamura Y, Hirai T. et al. Expression of CDX1 and CDX2 mRNAs and relevance of this expression to differentiation in human gastrointestinal mucosa with special emphasis on participation in intestinal metaplasia of the human stomach. Gastric Cancer 2001; 294: 470-9
• 7 Almeida R, Silva E, Santos-Silva F, Silberg DG, Wang J, De BolósC. et al. Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. J Pathol 2003; 199: 36-40
• 8 Satoh K, Mutoh H, Eda A, Yanaka I, Osawa H, Honda S. et al. Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia: Effect of eradication of Helicobacter pylori. Helicobacter 2002; 7: 192-8
• 9 Seno H, Oshima M, Taniguchi MA, Usami K, Ishikawa TO, Chiba T. et al. CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer: Prognostic implications. Int J Oncol 2002; 21: 769-74
• 10 Lazar D, Taban S, Sporea I, Dema A, Cornianu M, Lazar E. et al. Ki-67 expression in gastric cancer. Results from a prospective study with long-term follow-up. Rom J Morphol Embryol 2010; 51: 655-61
• 11 Yu J, He Y, Guo Z. Age trend of the male to female sex ratio in surgical gastric cancer patients at a single institution. World J Surg Oncol 2014; 12: 269
• 12 Janssen CWJr, Maartmann-Moe H, Lie RT, Matre R. Age and sex distribution of intestinal type and diffuse gastric carcinoma. APMIS 1991; 99: 78-82
• 13 Saha AK, Maitra S, Hazra SC. Epidemiology of gastric cancer in the gangetic areas of West Bengal. ISRN Gastroenterol 2013; 2013: 823483
• 14 Machida-Montani A, Sasazuki S, Inoue M, Natsukawa S, Shaura K, Koizumi Y. et al. Association of Helicobacter pylori infection and environmental factors in non-cardia gastric cancer in Japan. Gastric Cancer 2014; 7: 46-53
• 15 Lee YY, Derakhshan MH. Environmental and lifestyle risk factors of gastric cancer. Arch Iran Med 2013; 16: 358-65
• 16 Henson DE, Dittus C, Younes M, Nguyen H, Albores-Saavedra J. Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States, 1973-2000: Increase in the signet ring cell type. Arch Pathol Lab Med 2004; 128: 765-70
• 17 Wu H, Rusiecki JA, Zhu K, Potter J, Devesa SS. Stomach carcinoma incidence patterns in the United States by histologic type and anatomic site. Cancer Epidemiol Biomarkers Prev 2009; 1945: 52
• 18 Lundegårdh G, Lindgren A, Rohul A, Nyrén O, Hansson LE, Bergström R. et al Intestinal and diffuse types of gastric cancer: Secular trends in Sweden since 1951. Br J Cancer 1991; 64: 1182-6
• 19 Cambruzzi E, Azeredo AM, Kronhart A, Foltz KM, Zettler CG, Pêgas KL. The presence of metastases in regional lymph nodes is associated with tumor size and depth of invasion in sporadic gastric adenocarcinoma. Arq Bras Cir Dig 2014; 27: 18-21
• 20 Liu Y, Chen XH, Meng XH, Liu CF, Zhao LL, Han JW. et al. Multivariate prognostic study on node-positive gastric cancer: Is tumor size a prognostic indicator?. Hepatogastroenterology 2012; 59: 623-6
• 21 Folli S, Morgagni P, Roviello F, De ManzoniG, Marrelli D, Saragoni l. et al. Risk factors for lymph node metastases and their prognostic significance in early gastric cancer (EGC) for the Italian Research Group for Gastric Cancer (IRGGC). Jpn J Clin Oncol 2001; 31: 495-9
• 22 Ha KimG, Am SongG, Youn ParkD, Han LeeS, Hyun LeeD, Oh KimT. et al. CDX2 expression is increased in gastric cancers with less invasiveness and intestinal mucin phenotype. Scand J Gastroenterol 2006; 41: 880-6
• 23 Roessler K, Mönig SP, Schneider PM, Hanisch FG, Landsberg S, Thiele J. et al Co-expression of CDX2 and MUC2 in gastric carcinomas: Correlations with clinico-pathological parameters and prognosis. World J Gastroenterol 2005; 11: 3182-8
• 24 Fan Z, Li J, Dong B, Huang X. Expression of Cdx2 and hepatocyte antigen in gastric carcinoma: Correlation with histologic type and implications for prognosis. Clin Cancer Res 2005; 11: 6162-70
• 25 Ramires M, David L, Leitão D, Seixas M, Sansonetty F, Sobrinho-Simõe M. Ki67 labelling index in gastric carcinomas. An immunohistochemical study using double staining for the evaluation of the proliferative activity of diffuse-type carcinomas. J Pathol 1997; 182: 62-7