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

Mizoshita, Tsutomu; Tsukamoto, Tetsuya; Nakanishi, Hayao; Inada, Ken Ichi; Ogasawara, Nagahisa; Joh, Takashi; Itoh, Makoto; Yamamura, Yoshitaka; Tatematsu, Masae

doi:10.1007/s00432-003-0499-6

Cited by 114 publications

(169 citation statements)

References 40 publications

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“…For phenotypic expression analysis of GC, we performed immunohistochemical analysis (as described above) with 4 antibodies: anti-MUC5AC (Novocastra, Newcastle, UK) as a marker of foveolar epithelial cells in the stomach, anti-MUC6 (Novocastra) as a marker of pyloric gland cells in the stomach, anti-MUC2 (Novocastra) as a marker of goblet cells in the small intestine and colorectum and anti-CD10 (Novocastra) as a marker of microvilli of absorptive cells in the small intestine and colorectum. The criteria 19 for the classification of G type and I type GCs were as follows. GCs in which more than 10% of cells in the section expressed at least 1 gastric epithelial cell marker (MUC5AC or MUC6) or intestinal epithelial cell marker (MUC2 or CD10) were classified as G type or I type cancers, respectively.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Serum olfactomedin 4 (GW112, hGC‐1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients

Oue

Sentani

Noguchi

et al. 2009

Intl Journal of Cancer

104

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Gastric cancer (GC) is 1 of the most common human cancers. Early detection remains the most promising approach to improving long‐term survival of patients with GC. We previously performed Serial Analysis of Gene Expression (SAGE) on 4 primary GCs and identified several GC‐specific genes including Reg IV. Of these genes, olfactomedin 4 (OLFM4, also known as GW112 or hGC‐1) is a candidate gene for cancer‐specific expression. In this study, we examined the expression of olfactomedin 4 in human GC by immunohistochemistry. We also assessed serum olfactomedin 4 levels in GC patients by enzyme‐linked immunosorbent assay. 94 (56%) of 167 GC cases were positive for olfactomedin 4 by immunostaining. Olfactomedin 4 staining was observed more frequently in stage I/II cases than in stage III/IV cases. The serum olfactomedin 4 concentration in presurgical GC patients (n = 123, mean ± SE, 36.3 ± 3.5 ng/mL) was significantly higher than that in healthy individuals (n = 76, 16.6 ± 1.6 ng/mL). In patients with stage I GC, the sensitivity of serum olfactomedin 4 (25%) and Reg IV (35%) was superior to that of CA19‐9 (5%) or CEA (3%). Furthermore, in patients with stage I GC, the combination of olfactomedin 4 and Reg IV elevated the diagnostic sensitivity to 52%. These results suggest that serum olfactomedin 4 is a useful marker for GC and its measurement alone or in combination with Reg IV has utility in the early detection of GC. © 2009 UICC

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Section: Immunohistochemistrymentioning

confidence: 99%

Serum olfactomedin 4 (GW112, hGC‐1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients

Oue

Sentani

Noguchi

et al. 2009

Intl Journal of Cancer

104

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“…Determination of ABI Anaphase bridges were scored as described previously (Seno et al, 2002;Aoki et al, 2003;Mizoshita et al, 2003;Supplementary Information).…”

Section: Immunohistochemical Analysesmentioning

confidence: 99%

Chromosomal instability by β-catenin/TCF transcription in APC or β-catenin mutant cells

Aoki

Sugai

et al. 2006

Oncogene

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Adenomatous polyposis coli (APC/Apc) gene encodes a key tumor suppressor whose mutations activate b-catenin/ T-cell factor (TCF)-mediated transcription (canonical Wnt signaling). Here, we show that Wnt signaling can cause chromosomal instability (CIN). As an indicator of CIN, we scored anaphase bridge index (ABI) in mouse polyps and ES cells where Wnt signaling was activated by Apc or b-catenin mutations. We found three to nine times higher ABI than in wild-type controls. Furthermore, karyotype analysis confirmed that the Wnt signalactivated ES cells produced new chromosomal aberrations at higher rates; hence CIN. Consistently, expression of dominant-negative TCFs in these cells reduced their ABI. We also found that Wnt signal activation increased phosphorylation of Cdc2 (Cdk1) that inhibited its activity, and suppressed apoptosis upon exposure of the cells to nocodazole or colcemid. The data suggest that Wnt signaling stimulates the cells to escape from mitotic arrest and apoptosis, resulting in CIN. In human gastric cancer tissues with nuclear b-catenin, ABI was significantly higher than in those without. These results collectively indicate that b-catenin/TCF-mediated transcription itself increases CIN through dysregulation of G2/M progression.

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“…23 CDX2 expression is associated with not only intestinal mucin phenotypes, 14,24 but also an early tumor stage [24][25][26][27][28][29][30] and improved prognosis in patients with gastric cancer. [29][30][31][32] A previous study reported that CDX2 expression is also correlated with an improved prognosis in patients with ampullary adenocarcinomas. 33 Several previous studies have compared the protein expression profiles of gastric and colonic carcinomas and small intestinal adenocarcinomas because of the anatomical proximity and similarities between these cancers.…”

mentioning

confidence: 99%

Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma

et al. 2014

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The clinicopathological and prognostic significance of CDX2 and mucin expression have not been comprehensively evaluated in small intestinal adenocarcinoma. Immunohistochemical microarray analyses of CDX2, MUC1, MUC5AC, and MUC6 protein expressions in 189 surgically resected small intestinal adenocarcinoma cases were examined and compared with various clinicopathologic variables, including survival. CDX2, MUC1, MUC5AC, and MUC6 expressions were observed in 43.4% (82 patients), 37.6% (71), 31.7% (60), and 21.7% (41) of patients, respectively. Whereas CDX2 expression was found to be associated with lowgrade tumors (P ¼ 0.034), fewer nodal metastases (P ¼ 0.019), and less perineural invasion (P ¼ 0.049) in small intestinal adenocarcinoma patients, patients expressing MUC1 tended to demonstrate high-grade (P ¼ 0.021) and nodular or infiltrative (P ¼ 0.020) tumors. On the basis of the combined CDX2, MUC1, MUC5AC, and MUC6 expression patterns, small intestinal adenocarcinoma patients were further classified as intestinalAmong these immunophenotypes, intestinal-type patients demonstrated more frequent distal (jejunal or ileal; P ¼ 0.033), tubular (P ¼ 0.039), and low-grade tumors (P ¼ 0.004) and significantly better survival according to univariate (Po0.0001) and multivariate (P ¼ 0.001) analyses. In summary, intestinal immunophenotype adenocarcinomas are associated with distal (jejunal or ileal), tubular, and low-grade tumors and better survival outcomes. Hence, CDX2 and mucin immunohistochemical staining may provide better estimations of survival after surgical resection and intestinal immunophenotype could therefore be used as a better prognostic indicator of small intestinal adenocarcinoma. Modern Pathology (2014Pathology ( ) 27, 1364Pathology ( -1374 doi:10.1038/modpathol.2014 published online 7 March 2014 Keywords: adenocarcinoma; CDX2; immunohistochemistry; mucin; prognosis; small intestine Primary small intestinal adenocarcinomas account for only 5% of malignant neoplasms in the gastrointestinal tract despite the long length of the small intestine and the significant mucosal coverage over the entire gastrointestinal tract. 1 In 2013, it is estimated that 8810 Americans will be diagnosed with small intestinal adenocarcinoma. 1 Despite recent improvements in the detection of the small intestinal adenocarcinomas, including improved imaging techniques and endoscopic modalities, the diagnosis of small intestinal adenocarcinomas is usually made at an advanced clinical stage and the 5-year survival rate is only 41.2%. 2 Several clinicopathologic factors, including lymph node metastasis and the distal locations of these tumors (jejunum and ileum), are known as the most important independent prognostic factors. 2 Although several molecular alterations, including KRAS, TP53, and DPC4/SMAD4 mutations and the overexpression of cyclinD1, are known to be involved in small intestinal adenocarcinoma carcinogenesis, [3][4][5][6]

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

Cited by 114 publications

References 40 publications

Serum olfactomedin 4 (GW112, hGC‐1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients

Serum olfactomedin 4 (GW112, hGC‐1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients

Chromosomal instability by β-catenin/TCF transcription in APC or β-catenin mutant cells

Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma

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