Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Cancer Research and Clinical Oncology
Published in: Journal of Cancer Research and Clinical Oncology 12/2003

01-12-2003 | Original Paper

Expression of Cdx2 and the phenotype of advanced gastric cancers: relationship with prognosis

Authors: Tsutomu Mizoshita, Tetsuya Tsukamoto, Hayao Nakanishi, Ken-ichi Inada, Naotaka Ogasawara, Takashi Joh, Makoto Itoh, Yoshitaka Yamamura, Masae Tatematsu

Published in: Journal of Cancer Research and Clinical Oncology | Issue 12/2003

Login to get access

Abstract

Purpose

The clinicopathologic significance of the phenotype and Cdx2 expression has hitherto remained unclear in gastric cancers. In the present study, we therefore examined the correlation between prognosis, phenotype, and Cdx2 expression in advanced cases.

Methods

We evaluated 177 advanced gastric carcinomas histologically and phenotypically. The expression of Cdx2 was also assessed by immunohistochemistry.

Results

The lesions were phenotypically divided into 32 gastric (G type), 36 gastric and intestinal mixed (GI type), 53 intestinal (I type), and 56 null (N type) types, independent of the histological classification. Cdx2 nuclear staining demonstrated a close relation to intestinal phenotypic expression, not with the histological classification. Kaplan-Meier analysis of Cdx2 expression and the phenotype showed that the Cdx2 positive groups had a significantly better outcome than the negative ones (P =0.0013), and the patients with GI type cancers had significant better survival than those with N type (P =0.0052).

Conclusions

Our results suggest that Cdx2 is a useful prognostic marker. In addition, advanced gastric cancers with both intestinal and gastric phenotypic expression have a relatively good prognosis. Combined evaluation of gastric and intestinal epithelial cell markers, including Cdx2, is clinically useful to predict outcome in patients with advanced neoplasm of the stomach.
Literature
Almeida R, Silva E, Santos-Silva F, Silberg DG, Wang J, De Bolos C, David L (2003) Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. J Pathol 199:36–40CrossRefPubMed
Bai Y, Akiyama Y, Nagasaki H, Yagi OK, Kikuchi Y, Saito N, Takeshita K, Iwai T, Yuasa Y (2000) Distinct expression of CDX2 and GATA4/5, development-related genes, in human gastric cancer cell lines. Mol Carcinog 28:184–188CrossRefPubMed
Bai YQ, Yamamoto H, Akiyama Y, Tanaka H, Takizawa T, Koike M, Kenji Yagi O, Saitoh K, Takeshita K, Iwai T, Yuasa Y (2002) Ectopic expression of homeodomain protein CDX2 in intestinal metaplasia and carcinomas of the stomach. Cancer Lett 176:47–55CrossRefPubMed
Baldus SE, Zirbes TK, Engel S, Hanisch FG, Monig SP, Lorenzen J, Glossmann J, Fromm S, Thiele J, Pichlmaier H, Dienes HP (1998) Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas. Int J Cancer 79:133–138CrossRefPubMed
Baldus SE, Monig SP, Arkenau V, Hanisch FG, Schneider PM, Thiele J, Holscher AH, Dienes HP (2002) Correlation of MUC5AC immunoreactivity with histopathological subtypes and prognosis of gastric carcinoma. Ann Surg Oncol 9:887–893PubMed
Bamba M, Sugihara H, Kushima R, Okada K, Tsukashita S, Horinouchi M, Hattori T (2001) Time-dependent expression of intestinal phenotype in signet ring cell carcinomas of the human stomach. Virchows Arch 438:49–56PubMed
Ee HC, Erler T, Bhathal PS, Young GP, James RJ (1995) Cdx-2 homeodomain protein expression in human and rat colorectal adenoma and carcinoma. Am J Pathol 147:586–592PubMed
Egashira Y, Shimoda T, Ikegami M (1999) Mucin histochemical analysis of minute gastric differentiated adenocarcinoma. Pathol Int 49:55–61CrossRefPubMed
Gurbuz Y, Kahlke V, Kloppel G (2002) How do gastric carcinoma classification systems relate to mucin expression patterns? An immunohistochemical analysis in a series of advanced gastric carcinomas. Virchows Arch 440:505–511CrossRefPubMed
Ho SB, Shekels LL, Toribara NW, Kim YS, Lyftogt C, Cherwitz DL, Niehans GA (1995) Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium. Cancer Res 55:2681–2690PubMed
Inada K, Nakanishi H, Fujimitsu Y, Shimizu N, Ichinose M, Miki K, Nakamura S, Tatematsu M (1997) Gastric and intestinal mixed and solely intestinal types of intestinal metaplasia in the human stomach. Pathol Int 47:831–841PubMed
Inada K, Tanaka H, Nakanishi H, Tsukamoto T, Ikehara Y, Tatematsu K, Nakamura S, Porter EM, Tatematsu M (2001) Identification of Paneth cells in pyloric glands associated with gastric and intestinal mixed-type intestinal metaplasia of the human stomach. Virchows Arch 439:14–20CrossRefPubMed
Japanese Gastric Cancer Association (1998) Japanese Classification of Gastric Carcinoma - 2nd English Edition. Gastric Cancer 1:10–24CrossRefPubMed
Kawachi H, Takizawa T, Eishi Y, Shimizu S, Kumagai J, Funata N, Koike M (2003) Absence of either gastric or intestinal phenotype in microscopic differentiated gastric carcinomas. J Pathol 199:436–446CrossRefPubMed
Koseki K, Takizawa T, Koike M, Ito M, Nihei Z, Sugihara K (2000) Distinction of differentiated type early gastric carcinoma with gastric type mucin expression. Cancer 89:724–732CrossRefPubMed
Lauren P (1965) 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 64:31–49
Lee HS, Lee HK, Kim HS, Yang HK, Kim YI, Kim WH (2001) MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators. Cancer 92:1427–1434CrossRefPubMed
Lee HS, Lee HK, Kim HS, Yang HK, Kim WH (2003) Tumour suppressor gene expression correlates with gastric cancer prognosis. J Pathol 200:39–46CrossRefPubMed
Machado JC, Nogueira, AM, Carneiro F, Reis CA, Sobrinho-Simoes M (2000) Gastric carcinoma exhibits distinct types of cell differentiation: an immunohistochemical study of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC, and MUC6). J Pathol 190:437–443CrossRefPubMed
Mallo GV, Rechreche H, Frigerio JM, Rocha D, Zweibaum A, Lacasa M, Jordan BR, Dusetti NJ, Dagorn JC, Iovanna JL (1997) Molecular cloning, sequencing and expression of the mRNA encoding human Cdx1 and Cdx2 homeobox. Down-regulation of Cdx1 and Cdx2 mRNA expression during colorectal carcinogenesis. Int J Cancer 74:35–44CrossRefPubMed
Mallo GV, Soubeyran P, Lissitzky JC, Andre F, Farnarier C, Marvaldi J, Dagorn JC, Iovanna JL (1998) Expression of the Cdx1 and Cdx2 homeotic genes leads to reduced malignancy in colon cancer-derived cells. J Biol Chem 273:14030–14036CrossRefPubMed
Matsukuma A, Mori M, Enjoji M (1990) Sulphomucin-secreting intestinal metaplasia in the human gastric mucosa: an association with intestinal-type gastric carcinoma. Cancer 66:689–694PubMed
Mizoshita T, Inada K, Tsukamoto T, Kodera Y, Yamamura Y, Hirai T, Kato T, Joh T, Itoh M, Tatematsu, M (2001) 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 4:185–191PubMed
Nakamura K, Sugano H, Takagi K (1968) Carcinoma of the stomach in incipient phase: its histogenesis and histological appearances. Gann 59:251–258PubMed
Pinto-de-Sousa J, David L, Reis CA, Gomes R, Silva L, Pimenta A (2002) Mucins MUC1, MUC2, MUC5AC and MUC6 expression in the evaluation of differentiation and clinico-biological behaviour of gastric carcinoma. Virchows Arch 440:304–310CrossRefPubMed
Reis CA, David L, Carvalho F, Mandel U, de Bolos C, Mirgorodskaya E, Clausen H, Sobrinho-Simoes M (2000) Immunohistochemical study of the expression of MUC6 mucin and co-expression of other secreted mucins (MUC5AC and MUC2) in human gastric carcinomas. J Histochem Cytochem 48:377–388PubMed
Seno H, Oshima M, Taniguchi MA, Usami K, Ishikawa TO, Chiba T, Taketo MM (2002) CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer: Prognostic implications. Int J Oncol 21:769–774PubMed
Silberg DG, Swain GP, Suh ER, Traber PG (2000) Cdx1 and cdx2 expression during intestinal development. Gastroenterology 119:961–971PubMed
Silberg DG, Sullivan J, Kang E, Swain GP, Moffett J, Sund NJ, Sackett SD, Kaestner KH (2002) Cdx2 ectopic expression induces gastric intestinal metaplasia in transgenic mice. Gastroenterology 122:689–696PubMed
Sugano H, Nakamura K, Kato Y (1982) Pathological studies of human gastric cancer. Acta Pathol Jpn 32 [Suppl 2]: 329–347
Tajima Y, Shimoda T, Nakanishi Y, Yokoyama N, Tanaka T, Shimizu K, Saito T, Kawamura M, Kusano M, Kumagai K (2001) Gastric and intestinal phenotypic marker expression in gastric carcinomas and its prognostic significance: immunohistochemical analysis of 136 lesions. Oncology 61:212–220CrossRefPubMed
Tanaka M, Kitajima Y, Sato S, Miyazaki K (2003) Combined evaluation of mucin antigen and E-cadherin expression may help select patients with gastric cancer suitable for minimally invasive therapy. Br J Surg 90:95–101CrossRefPubMed
Tatematsu M, Furihata C, Katsuyama T, Hasegawa R, Nakanowatari J, Saito D, Takahashi M, Matsushima T, Ito N (1983) Independent induction of intestinal metaplasia and gastric cancer in rats treated with N-methyl-N’-nitro-N-nitrosoguanidine. Cancer Res 43:1335–1341PubMed
Tatematsu M, Katsuyama T, Furihata C, Tsuda H, Ito N (1984) Stable intestinal phenotypic expression of gastric and small intestinal tumor cells induced by N-methyl-N’-nitro-N-nitrosoguanidine or methylnitrosourea in rats. Gann 75:957–965PubMed
Tatematsu M, Furihata C, Katsuyama T, Miki K, Honda H, Konishi Y, Ito N (1986) Gastric and intestinal phenotypic expressions of human signet ring cell carcinomas revealed by their biochemistry, mucin histochemistry, and ultrastructure. Cancer Res 46:4866–4872PubMed
Tatematsu M, Ichinose M, Miki K, Hasegawa R, Kato T, Ito N (1990) Gastric and intestinal phenotypic expression of human stomach cancers as revealed by pepsinogen immunohistochemistry and mucin histochemistry. Acta Pathol Jpn 40:494–504PubMed
Tatematsu M, Hasegawa R, Ogawa K, Kato T, Ichinose M, Miki K, Ito N (1992) Histogenesis of human stomach cancers based on assessment of differentiation. J Clin Gastroenterol 14 [Suppl 1]: S1–7
Tatematsu M, Fukami H, Yamamoto M, Nakanishi H, Masui T, Kusakabe N, Sakakura T (1994) Clonal analysis of glandular stomach carcinogenesis in C3H/HeN⇔BALB/c chimeric mice treated with N-methyl-N-nitro-N-nitrosourea. Cancer Lett 83:37–42
Tatematsu M, Tsukamoto T, Inada K (2003) Stem cells and gastric cancer: role of gastric and intestinal mixed intestinal metaplasia. Cancer Sci 94:135–141PubMed
Tsuchiya A, Kikuchi Y, Ando Y, Abe R (1995) Correlation between expression of sialosyl-T antigen and survival in patients with gastric cancer. Br J Surg 82:960–962PubMed
Utsunomiya T, Yonezawa S, Sakamoto H, Kitamura H, Hokita S, Aiko T, Tanaka S, Irimura T, Kim YS, Sato E (1998) Expression of MUC1 and MUC2 mucins in gastric carcinomas: its relationship with the prognosis of the patients. Clin Cancer Res 4:2605–2614PubMed
Vider BZ, Zimber A, Hirsch D, Estlein D, Chastre E, Prevot S, Gespach C, Yaniv A, Gazit A (1997) Human colorectal carcinogenesis is associated with deregulation of homeobox gene expression. Biochem Biophys Res Commun 232:742–748CrossRefPubMed
Werling RW, Yaziji H, Bacchi CE, Gown AM (2003) CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol 27:303–310CrossRefPubMed
Yamachika T, Inada K, Fujimitsu Y, Nakamura S, Yamamura Y, Kitou T, Itzkowitz SH, Werther JL, Miki K, Tatematsu M (1997) Intestinalization of gastric signet ring cell carcinomas with progression. Virchows Arch 431:103–110CrossRefPubMed
Yoshikawa A, Inada Ki K, Yamachika T, Shimizu N, Kaminishi M, Tatematsu M (1998) Phenotypic shift in human differentiated gastric cancers from gastric to intestinal epithelial cell type during disease progression. Gastric Cancer 1:134–141PubMed
Yuasa H, Inada K, Watanabe H, Tatematsu M (2002) A phenotypic shift from gastric-intestinal to solely intestinal cell types in intestinal metaplasia in rat stomach following treatment with X-rays. J Toxicol Pathol 15:85–93CrossRef
Metadata
Title
Expression of Cdx2 and the phenotype of advanced gastric cancers: relationship with prognosis
Authors
Tsutomu Mizoshita
Tetsuya Tsukamoto
Hayao Nakanishi
Ken-ichi Inada
Naotaka Ogasawara
Takashi Joh
Makoto Itoh
Yoshitaka Yamamura
Masae Tatematsu
Publication date
01-12-2003
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 12/2003
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-003-0499-6

Other articles of this Issue 12/2003

Journal of Cancer Research and Clinical Oncology 12/2003 Go to the issue

Rapid Communication

Expression of a novel lacrimal gland gene lacritin in human breast tissues

Original Paper

EphA2 Up-regulation induced by deoxycholic acid in human colon carcinoma cells, an involvement of extracellular signal-regulated kinase and p53-independence

Original Paper

Status of p53 phosphorylation and function in sensitive and resistant human cancer models exposed to platinum-based DNA damaging agents

Original Paper

Comparison of health-related quality of life and prostate-associated symptoms after primary and salvage cryotherapy for prostate cancer

Original Paper

Epidemiological aspects of cancer screening in Germany

Original Paper

Increased expression of CEA and MHC class I in colorectal cancer cell lines exposed to chemotherapy drugs
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits