Expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma: an immunopathological study with clinical correlation

Chinyama, Catherine N.; Marshall, Robert; Owen, William J.; Mason, Robert C.; Kothari, Darshan; Wilkinson, Mark D.; Sanderson, J

doi:10.1046/j.1365-2559.1999.00791.x

Cited by 66 publications

(65 citation statements)

References 22 publications

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“…HOXB5, HOXB6, and HOXB7 can activate some, but not all the intestinal makers commonly expressed in BE (36)(37)(38). Although this finding could depend on the transient nature of the transfection, it indicates that in the cell line model tested these genes do not induce a full intestinal phenotype and that other transcriptional factors may be required.…”

Section: Discussionmentioning

confidence: 92%

Evidence for a functional role of epigenetically regulated midclusterHOXBgenes in the development of Barrett esophagus

Pietro

Lao‐Sirieix

Boyle

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Barrett esophagus (BE) is a human metaplastic condition that is the only known precursor to esophageal adenocarcinoma. BE is characterized by a posterior intestinal-like phenotype in an anterior organ and therefore it is reminiscent of homeotic transformations, which can occur in transgenic animal models during embryonic development as a consequence of mutations in HOX genes. In humans, acquired deregulation of HOX genes during adulthood has been linked to carcinogenesis; however, little is known about their role in the pathogenesis of premalignant conditions. We hypothesized that HOX genes may be implicated in the development of BE. We demonstrated that three midcluster HOXB genes (HOXB5, HOXB6, and HOXB7) are overexpressed in BE, compared with the anatomically adjacent normal esophagus and gastric cardia. The midcluster HOXB gene signature in BE is identical to that seen in normal colonic epithelium. Ectopic expression of these three genes in normal squamous esophageal cells in vitro induces markers of intestinal differentiation, such as KRT20, MUC2, and VILLIN. In BE-associated adenocarcinoma, the activation midcluster HOXB gene is associated with loss of H3K27me3 and gain of AcH3, compared with normal esophagus. These changes in histone posttranslational modifications correlate with specific chromatin decompaction at the HOXB locus. We suggest that epigenetically regulated alterations of HOX gene expression can trigger changes in the transcriptional program of adult esophageal cells, with implications for the early stages of carcinogenesis. metaplasia | Homeobox | cancer | chromatin compaction | epigenetics

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Section: Discussionmentioning

confidence: 92%

Evidence for a functional role of epigenetically regulated midclusterHOXBgenes in the development of Barrett esophagus

Pietro

Lao‐Sirieix

Boyle

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…The differential diagnosis of melanocytic tumors is based on the expression of several proteins, such as S-100B [3, 4, 5]. HMB-45 or the recently introduced MART-1/Melan-A [4, 19]. S-100B is a useful marker since its expression is independent of the melanization [20], in contrast to other markers.…”

Section: Discussionmentioning

confidence: 99%

Heterogenous S-100B Protein Expression Patterns in Malignant Melanoma and Association with Serum Protein Levels

Bánfalvi¹,

Udvarhelyi

Orosz

et al. 2003

Oncology

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Objective: Serum S-100B is a reliable tumor marker of malignant melanoma, but efficient use is restricted to patients with metastatic disease. Therefore, the aim of our study was to assess serum S-100B levels at different stages of malignant melanoma and to compare these levels with the expression of the S-100B phenotype in primary tumors and lymph node metastases. Methods: Fifty-nine patients were included in this study; serum S-100B protein was measured using an immunoluminometric assay while the expression pattern in the primary tumor was determined by immunohistochemistry using an anti-S-100B monoclonal antibody. Results: Serum S-100B concentrations were significantly elevated in stage III (p = 0.01) patients, with normal levels in stage I–II. The most frequent S-100B protein expression pattern of the melanoma tissue was found to be diffuse staining observed in around half of the cases (52.5%) followed by heterogeneous (30.5%) and focal patterns (17%), being independent of the stage as well as the lymph node involvement. In stage I–II patients, the various staining patterns did not correlate with the serum concentration of the S-100B protein, while in stage III patients with heterogenous or diffuse S-100B staining patterns in tumor tissue, the serum marker concentration was significantly higher (p < 0.05) than in patients with focal staining. Furthermore, S-100B staining of the melanoma tissue also differed (low/negative, medium and strong staining), and serum marker concentrations corresponded to the pattern of the staining intensity. In stage I–II, only strong staining was associated with elevated serum S-100B concentrations while in stage III medium and strong staining was found to be associated with significantly higher serum marker concentrations compared to patients with tumors with low/negative staining (p < 0.05). Conclusions: In malignant melanoma characterized by focal and/or low S-100B staining in the tumor tissue determined by immunohistochemistry, S-100B monitoring in the serum may not suffice to detect disease progression.

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“…[6][7][8][9][10] It is well known that Barrett's oesophagus consists of two secreted mucin phenotypes, namely gastricand intestinal-predominant mucin phenotypes, and that the latter phenotype has a more malignant potential. [11][12][13] A number of investigators have reported that…”

Section: Introductionmentioning

confidence: 99%

Efficacy of proton pump inhibitors for cellular proliferation and apoptosis in Barrett's oesophagus with different mucin phenotypes

Amano

Chinuki

Yuki

et al. 2006

Aliment Pharmacol Ther

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Expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma: an immunopathological study with clinical correlation

Cited by 66 publications

References 22 publications

Evidence for a functional role of epigenetically regulated midclusterHOXBgenes in the development of Barrett esophagus

Evidence for a functional role of epigenetically regulated midclusterHOXBgenes in the development of Barrett esophagus

Heterogenous S-100B Protein Expression Patterns in Malignant Melanoma and Association with Serum Protein Levels

Efficacy of proton pump inhibitors for cellular proliferation and apoptosis in Barrett's oesophagus with different mucin phenotypes

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