Mucins MUC1, MUC2, MUC5AC and MUC6 expression in the evaluation of differentiation and clinico-biological behaviour of gastric carcinoma

Pinto-de-Sousa, João; David, Leonor; Reis, Celso A.; Gomes, Rui; Silva, Liliana; Pimenta, Amadeu

doi:10.1007/s00428-001-0548-y

Cited by 89 publications

(85 citation statements)

References 44 publications

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“…MUC2, the intestinal mucin, expressed in most of the studied cases (86%), higher than that in other studies [15] , However our result was in accordance with other results concerning its overwhelming expression in mucinous carcinomas [15,16] . Contradictory to some reports that MUC2 indicated good prognosis [9] , our study found that MUC2 could predict poor outcome.…”

Section: Discussionsupporting

confidence: 91%

Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance

Zhang

Zhang²,

Zhao³

et al. 2004

WJG

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AIM:To investigate the expression of three types of mucin (MUC1, MUC2, MUC5AC) and E-cadherin in human gastric carcinomas and their clinical significance. METHODS:Ninety-four gastric cancer specimens were classified according to WHO criteria and detected by immunohistochemical assay of expression of mucins and E-cadherin. RESULTS:The positive expression rates of MUC1, MUC2, MUC5AC and E-cadherin were 82% (77/94), 84% (79/94), 40% (38/94) and 56% (53/94) respectively. MUC1 expression was significantly correlated with the types of cancer (the positive rates of MUC1 in well and moderately differentiated tubular adenocarcinoma, poorly differentiated adenocarcinoma, signet-ring cell carcinoma and mucinous carcinoma were 91%, 87%, 71%, 71%, respectively, P<0.05), age of patients (the positive rates of it among the people who are younger than 40 years, between 40-60 years and over 60 year were 74%, 81%, 89%, P<0.05), lymph nodes involvement (the positive rates in the non-interfered group and the interfered group were 78%, 85%, P<0.05) and tumor size (the positive rates in the tumors with the size less than 3 cm, 3-6 cm and larger than 6 cm were 69%, 92%, 69%, P<0.05); MUC2 expression was significantly associated with types of cancers and had the strongest expression in mucinous carcinomas (the positive rates of MUC2 in well and moderately differentiated tubular adenocarcinoma, poorly differentiated adenocarcinoma, signet-ring cell carcinoma and mucinous carcinoma were 94%, 70%, 81%, 100%, P<0.05), but it had no obvious relation to age, gender, tumor location, lymph nodes involvement, depth of invasion and metastasis to extra-gastric organs (P>0.05); MUC5AC expression was not related to any of the characteristics investigated except that it had relation to gender, whereas MUC5AC showed the tendency to higher expression in less invasive lesions and lower expression in advanced stage cancers (P>0.05); No significant difference was found for E-cadherin expression. There were strong positive relationships between the expression of MUC1 and E-cadherin, MUC2 and E-cadherin, MUC1 and MUC2 (R = 0.33, R = 0.22, R = 0.32, respectively, P<0.05). According to the COX proportional hazards model, older patients, involvement of lymph nodes, different types of gastric cancer and MUC2 expression were significantly associated with poorer outcome of gastric carcinoma patients (β = 0.08, β = 3.94, β = 1.33, β = 0.75, respectively, P<0.05).CONCLUSION: MUC1 and MUC2 are good markers of different types of gastric cancer. MUC2 is especially a good marker of mucinous carcinoma. MUC1, MUC2 may interfere with the function of E-cadherin in gastric carcinomas, and have synergic effect on progression of gastric cancers.Zhang HK, Zhang QM, Zhao TH, Li YY, Yi YF. Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance.

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Section: Discussionsupporting

confidence: 91%

Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance

Zhang

Zhang²,

Zhao³

et al. 2004

WJG

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“…It is important to emphasize that some studies demonstrated how the biological behavior of a tumor with a gastric phenotype was comparable to an undifferentiated tumor (19,50,56) . There is no consensus on the nature and number of antibodies that might be used to define a mucin phenotype of gastric carcinoma, or what percentage of positive tumor cells in each staining section must be used (3,19,21,22,23,24,28,42,51,56,63,67) . Shiroshita et al (52) suggested that to define a gastric phenotype, MUC5AC mucin or HGM must present in foveolar cells and MUC6 mucin, as well as in cells of the pyloric gland, which are part of the minimal panel to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Mucin Phenotype Can Predict Gastric Cancer Recurrence After Endoscopic Mucosal Resection

Hondo

Kishi

Safatle‐Ribeiro

et al. 2017

Arq. Gastroenterol.

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-Background -Endoscopic mucosal resection is still considered an accepted treatment for early gastric cancer for selected cases. Histopathologic criteria for curative endoscopic resection are intramucosal well-differentiated adenocarcinoma, lateral and deep margins free of tumor, no histological ulceration, and no venous or lymphatic embolism. A 5% local recurrence rate has been described even when all the above-mentioned criteria are met. On the other hand, antigen expression by tumoral cells has been related to the biological behavior of several tumors. Objective -To evaluate whether early gastric cancer mucin immunoexpression, p53 and Ki-67, can predict recurrence after endoscopic mucosal resection, even when standard histopathologic criteria for curative measures have been attempted. Methods -Twenty-two patients with early gastric cancer were considered to have been completely resected by endoscopic mucosal resection. Local recurrence occurred in 5/22 (22.7%). Immunohistochemical study was possible in 18 (81.8%) resected specimens. Patients were divided in two groups: those with and those without local recurrence. They were compared across demographic, endoscopic, histologic data, and immunohistochemical factors for MUC2, MUC5a, CD10, p53, and Ki-67. Results -Mucin immunoexpression allowed a reclassification of gastric adenocarcinoma in intestinal (10), gastric (2), mixed (4), and null phenotypes (2). Mixed phenotype (positive for both MUC2 and MUC5a) was found in 80% of cases in the local recurrence group, while the intestinal type (positive MUC2 and negative MUC5a) was found in 76.9% of cases without local recurrence (P=0.004). Other observed features did not correlate with neoplastic recurrence. Conclusion -The mixed phenotype of early gastric adenocarcinoma is associated with a higher probability of local recurrence after endoscopic mucosal resection.HEADINGS -Stomach neoplasms. Endoscopic mucosal resection. Gastric mucins.

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“…Immunohistochemical staining was performed on the tissue microarray sections, using a panel of markers previously reported to be indicators of intestinal (CDX2, CD10, MUC2) [21][22][23] or gastric (MU-C5AC, MUC6) [23][24][25][26] phenotype. Nuclear b-catenin and MUC1 expression-previously reported to be prognostic biomarkers for adenocarcinomas of the stomach and esophagus 27-29 -was also evaluated.…”

Section: Immunohistochemical Analysesmentioning

confidence: 99%

The dichotomy in carcinogenesis of the distal esophagus and esophagogastric junction: intestinal-type vs cardiac-type mucosa-associated adenocarcinoma

et al. 2011

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Adenocarcinoma of the distal esophagus and esophagogastric junction continues to rise in incidence. An intestinal metaplasia (Barrett esophagus)-dysplasia-carcinoma sequence induced by gastroesophageal reflux disease is well established. However, a significant number of adenocarcinomas in the vicinity of the esophagogastric junction are seen in the background of gastric/cardiac-type mucosa without intestinal metaplasia. Thus, the aim of this study was to investigate the role of Barrett esophagus (intestinal-type mucosa) in the classification and prognosis of tumors of the distal esophagus and esophagogastric junction. Clinicopathological and molecular characteristics were examined in 157 consecutively resected adenocarcinomas of the distal esophagus and esophagogastric junction and were compared between tumors arising in association with intestinal-type and cardiac-type mucosa. Intestinal-type mucosa-associated adenocarcinomas were more likely to be associated with younger age (P ¼ 0.0057), reflux symptoms (Po0.0001), proximal location (P ¼ 0.0009), lower T stage (Po0.0001), fewer nodal metastases (P ¼ 0.0001), absence of lymphatic (Po0.0001), venous (P ¼ 0.0060) or perineural (Po0.0001) invasion. Histologically, intestinal-type mucosa-associated tumors were more likely to be low-grade glandular tumors (P ¼ 0.0095) of intestinal or mixed immunophenotype (P ¼ 0.015) and express nuclear b-catenin (P ¼ 0.0080), whereas tumors arising in a background of cardiac-type mucosa were more frequently associated with EGFR amplification (P ¼ 0.0051). Five-year overall survival rate was significantly higher in patients with intestinal-type mucosa-associated tumors (28 vs 9%, P ¼ 0.0015), although no survival benefit was seen after adjusting for potential confounders. Our findings support the theory that multiple distinct pathways of tumorigenesis exist in the vicinity of the esophagogastric junction, including one in which tumors arise from dysplastic intestinal metaplasia (intestinal pathway), and one potentially involving dysplasia of the cardiac-type mucosa (non-intestinal pathway). Additional studies are warranted to further clarify their pathogenesis and the molecular mechanisms involved.

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Mucins MUC1, MUC2, MUC5AC and MUC6 expression in the evaluation of differentiation and clinico-biological behaviour of gastric carcinoma

Cited by 89 publications

References 44 publications

Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance

Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance

Characterization of the Mucin Phenotype Can Predict Gastric Cancer Recurrence After Endoscopic Mucosal Resection

The dichotomy in carcinogenesis of the distal esophagus and esophagogastric junction: intestinal-type vs cardiac-type mucosa-associated adenocarcinoma

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