CDX2 co‐localizes with liver–intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach

Ko, Samuel; Chu, Kent‐Man; Luk, John M.; Wong, Bonnie; Yuen, Siu‐Tsan; Leung, Suet Yi; Wong, John

doi:10.1002/path.1741

Cited by 36 publications

(38 citation statements)

References 36 publications

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“…[15][16][17][18][19][20] In the present study, nuclear expression of CDX2 was observed in the great majority of cases of intestinal metaplasia of the urinary bladder, which is not an unexpected finding considering the regulatory role of CDX2 in intestinal differentiation. In sharp contrast, no case of typical cystitis glandularis revealed similar nuclear staining.…”

Section: Discussionmentioning

confidence: 63%

“…The gene product, CDX2 protein, was initially identified in epithelial cells throughout the small and large intestines, and is believed to play a critical role in the differentiation and maintenance of intestinal epithelium via the regulation of intestine-specific gene transcription. [10][11][12][13][14] Subsequent studies have demonstrated its expression in adenocarcinomas in the esophagus, stomach, ovary, uterus, and lung, [15][16][17][18][19][20] as well as in intestinal metaplasia in the upper gastrointestinal tract and the gall bladder. 18,[21][22][23][24] Hepatocyte-specific antigen (Hep) is a cytoplasmic antigen initially identified in normal hepatocytes and in hepatic neoplasia.…”

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confidence: 99%

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Divergent pathway of intestinal metaplasia and cystitis glandularis of the urinary bladder

et al. 2006

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Intestinal metaplasia has been proposed to be a precursor lesion of adenocarcinoma in the urinary bladder. CDX2 is a transcription factor that is encoded by a homeotype gene that plays an essential role in the differentiation and proliferation of intestinal epithelial cells. Hepatocyte-specific antigen (Hep) has also been shown to be a useful marker of intestinal metaplasia. Tissues from 46 patients, including 22 cases of intestinal metaplasia of the urinary bladder, 11 cases of typical cystitis glandularis, and 13 cases containing both lesions, were selected and immunohistochemical stains for CDX2, Hep, cytokeratin 20 (CK20), and cytokeratin 7 (CK7) were performed. Nuclear staining for CDX2 was observed in 29 of 35 (83%) cases of intestinal metaplasia of the urinary bladder. In contrast, nuclear staining for CDX2 was not observed in any case of typical cystitis glandularis; however, seven of 24 (29%) cases showed aberrant cytoplasmic expression in a mean of 37% of cells. CK20 was expressed in 28 of 35 (80%) cases of intestinal metaplasia, but was observed in only one of 24 (4%) cases of cystitis glandularis in 15% of cells. CK7 was expressed in only six of 35 (17%) cases of intestinal metaplasia, whereas expression of CK7 was observed in all cases (100%) of typical cystitis glandularis with a mean percentage of positively staining cells of 63%. The mean percentages of positively staining cells in intestinal metaplasia with CDX2, CK20, and CK7 were 55, 49, and 53%, respectively. All examples of both intestinal metaplasia and typical cystitis glandularis were uniformly negative for Hep. In the urinary bladder, intestinal metaplasia and typical cystitis glandularis have sharply contrasting immunoprofiles. Additionally, the absence of Hep staining in intestinal metaplasia of the urinary bladder, despite its morphologic resemblance to normal colonic mucosa and intestinal metaplasia in other organs, may signify the presence of unique metaplastic pathways in the urinary bladder. Keywords: urinary bladder; cystitis glandularis; intestinal metaplasia; CDX2; hepatocyte-specific antigen; cytokeratin 20Cystitis glandularis is a metaplastic alteration of the urothelium in the urinary bladder that is thought to be induced by chronic inflammation or irritation.

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Section: Discussionmentioning

confidence: 63%

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confidence: 99%

Divergent pathway of intestinal metaplasia and cystitis glandularis of the urinary bladder

et al. 2006

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“…Several studies have shown significant expression of CDX2 in adenocarcinomas and intestinal metaplasia at various sites (31,32). In the urinary tract, immunoreactivity to CDX2 has been reported in up to 83% of cases of intestinal metaplasia (13) and in 47% of primary adenocarcinomas (33), suggesting that intestinal differentiation is an inherent characteristic of most sporadic primary vesical adenocarcinomas.…”

Section: Discussionmentioning

confidence: 99%

Histogenesis of Clear Cell Adenocarcinoma in the Urinary Tract: Evidence of Urothelial Origin

Sung

Zhang²,

MacLennan

et al. 2008

Clinical Cancer Research

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Purpose: Clear cell adenocarcinoma in the urinary tract is a rare entity with an appearance resembling its counterpart in the female genital tract. Although several theories have been proposed about its origin, its exact histogenesis has remained uncertain. Experimental Design: We integrated molecular genetic evaluation by fluorescence in situ hybridization and X-chromosome inactivation with conventional morphologic and immunohistochemical analyses in 12 patients with clear cell adenocarcinomas in the urinary tract. Results: Concurrent urothelial carcinoma or urothelial carcinoma in situ was present in six cases (50%) and foci of cystitis glandularis were observed in four cases (33%). Neither intestinal metaplasia nor Mu« llerian component was identified in any case. Cytoplasmic expression of a-methylacyl-CoA racemase was demonstrable in 10 of 12 tumors (83%). Moderate to diffuse immunostaining for cytokeratin 7 was identified in all 12 tumors (100%), whereas only 3 of 12 (25%) tumors showed positive immunostaining for cytokeratin 20. Focal uroplakin III staining was seen in 6 of 12 tumors (50%). In five cases (42%), focal to moderate CD10 immunoreactivity was observed. Immunostains for OCT4 and CDX2 were completely negative in all tumors. In UroVysion fluorescence in situ hybridization assays, all tumors displayed chromosomal alterations similar to those commonly found in urothelial carcinoma. Identical patterns of nonrandom X-chromosome inactivation in concurrent clear cell adenocarcinoma and urothelial neoplasia were identified in two informative female cases. Conclusions: Our findings support an urothelial origin for most clear cell adenocarcinomas of the urinary tract, despite their morphologic resemblance to certain Mu« llerian-derived tumors of the female genital tract.Clear cell adenocarcinoma in the urinary tract is an extremely rare neoplasm predominantly occurring in adult females and morphologically identical to tumors of the same name that arise in female genital organs. Its precise histogenesis has remained controversial. It has been postulated to be of mesonephric origin (1), Mü llerian origin (2 -4), or urothelial origin (5, 6). The histogenetic connection between clear cell adenocarcinoma and adenocarcinoma of non-Mü llerian type has been addressed by some investigators (6), and others have suggested that it results from malignant transformation of nephrogenic adenoma (7,8). Previous investigations of its histogenesis have involved morphologic or immunohistochemical analyses of single cases or small series of cases. In our current study, we evaluated a large series of cases of clear cell adenocarcinoma of the urinary tract by molecular genetic appraisal with fluorescence in situ hybridization (FISH) and integrated these findings with conventional morphologic and immunohistochemical analyses in an effort to elucidate the histogenesis of this rare and enigmatic neoplasm. Materials and MethodsCases diagnosed as clear cell adenocarcinoma in the urinary tract were retrieved from the surgical...

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“…25 It has recently become more evident that such an adhesion molecule plays an important role during the process of invasion or metastasis in colorectal, liver and gastric cancers, 13,[26][27][28] not only considered as a static intercellular glue. During the last couple of years, accumulating evidence suggested that high expression of CDH17 is associated with high metastatic potential, positive lymph node metastasis and short overall survival in gastric cancer patients.…”

Section: Resultsmentioning

confidence: 99%

Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NFκB signaling pathway

Wang

Kang

et al. 2013

Cancer Biology & Therapy

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CDX2 co‐localizes with liver–intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach

Cited by 36 publications

References 36 publications

Divergent pathway of intestinal metaplasia and cystitis glandularis of the urinary bladder

Divergent pathway of intestinal metaplasia and cystitis glandularis of the urinary bladder

Histogenesis of Clear Cell Adenocarcinoma in the Urinary Tract: Evidence of Urothelial Origin

Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NFκB signaling pathway

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