Expression of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas: Its relationship with tumor progression and prognosis

Tamada, Shugo; Goto, Masamichi; Nomoto, Mitsuharu; Nagata, Koji; Shimizu, Takeshi; Tanaka, Sadao; Sakoda, Koro; Imai, K; Yonezawa, Suguru

doi:10.1046/j.1440-1827.2002.01414.x

Cited by 76 publications

(82 citation statements)

References 35 publications

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“…agreement with findings of previous reports (16,17). Several experimental studies may explain the finding that MUC1 expression is correlated with tumor progression (9)(10)(11)18,19).…”

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confidence: 91%

Expression of MUC1, MUC2, MUC5AC and MUC6 in cholangiocarcinoma: Prognostic impact

Park

Roh²,

Kim³

et al. 2009

Oncol Rep

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Abstract. Mucin is a high molecular weight glycoprotein that plays an important role to protect the gastrointestinal tract epithelium. However, in cancer cells and during cancer progression, the expression profile of mucins is altered and expression of some mucins is correlated with prognosis for certain malignancies. The aim of this study was to determine the relationship between the expression of MUC1, MUC2, MUC5AC and MUC6 in cholangiocarcinoma and clinicopathological parameters as well as patient survival. In addition, this study was performed to identify whether immunohistochemical staining for mucins is useful to differentiate cholangiocarcinoma from adenocarcinoma of the pancreas and gallbladder. Immunohistochemical staining for MUC1, MUC2, MUC5AC and MUC6 was performed for 85 cases of cholangiocarcinoma, including 34 cases of intrahepatic cholangiocarcinoma (ICC), 51 cases of extrahepatic cholangiocarcinoma (ECC), 11 cases of gallbladder adenocarcinoma and 14 cases of pancreas adenocarcinoma. For cholangiocarcinomas, positivity of immunohistochemical staining for MUC1, MUC2, MUC5AC and MUC6 was 65.8, 23.5, 61.1 and 14.1%, respectively. For cholangiocarcinomas, MUC1 positivity was determined to be statistically significant for poor differentiation (p=0.002), T category (p=0.003), gross type (ICC, p=0.005; ECC, p=0.006) and poor patient survival (p=0.015). MUC5AC was more frequently expressed in advanced tumors (p=0.013). MUC6 expression was significantly detected in well-differentiated cholangiocarcinomas (p=0.006). There was no significant difference for the mucin staining patterns of cholangiocarcinomas, pancreatic adenocarcinomas and gallbladder adenocarcinomas. These results indicate that MUC1 expression in cholangiocarcinomas is closely related to dedifferentiation, infiltrative growth pattern and patient survival. Our results suggest that the expression of MUC1 might be associated with the progression of cholangiocarcinoma.

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“…agreement with findings of previous reports (16,17). Several experimental studies may explain the finding that MUC1 expression is correlated with tumor progression (9)(10)(11)18,19).…”

Section: ------------------------------------------------------------supporting

confidence: 91%

Expression of MUC1, MUC2, MUC5AC and MUC6 in cholangiocarcinoma: Prognostic impact

Park

Roh²,

Kim³

et al. 2009

Oncol Rep

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“…MUC1 is important in the invasiveness and metastatic potential of CC, and usually correlates with a decreased survival (23)(24)(25). In contrast to MUC1, MUC2 acts as a protective protein and is associated with a more favorable prognosis (26,27). MUC5AC is a gel-forming secreted mucin and serum MUC5AC is likely to be a poor prognostic factor in CC patients (28,29).…”

Section: Discussionmentioning

confidence: 99%

Expression of keratin 20 and its clinicopathological significance in intrahepatic cholangiocarcinoma

Choi¹,

Noh²,

Lee³

et al. 2012

Oncology Letters

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Abstract. Although the expression of keratin 7 (K7) and K20 is considered to be a useful factor in the differential diagnosis of intrahepatic cholangiocarcinoma (ICC) and metastatic colorectal carcinoma (CRC) of the liver, a proportion of typical ICC retains K20 expression. The frequency and biological significance of K20 expression in ICC remains unclear. We analyzed the expression of K7, K19 and K20 in 66 surgically resected liver tumors consisting of 46 ICCs and 20 metastatic CRCs of the liver and 20 corresponding primary CRCs. In the 46 ICCs, K7, K19 and K20 were expressed in 40 (87%), 45 (98%) and 16 (35%) cases, respectively. K7, K19 and K20 were expressed in 1 (5%), 20 (100%) and 16 (80%) of the 20 primary CRCs and 2 (10%), 20 (100%) and 16 (80%) of the 20 metastatic CRCs, respectively. A combined K7/K20 profile was identified as a good predictor for differentiating ICC and metastatic CRC. K20 expression in ICC was significantly associated with male gender (P=0.034), hilar location (P=0.026), intraductal papillary type (P=0.006), intestinal phenotype (P<0.001) and MUC2 expression (P=0.008). Univariate analysis identified that poor patient survival was significantly associated with histological grade (P=0.020), invasion depth (P=0.005), lymph node metastasis (P=0.012), tumor stage (P=0.004) and vessel invasion (P=0.023). The tumor stage (P=0.002) was a poor independent prognostic indicator, while MUC6 expression (P=0.036) was a good independent prognostic indicator. The survival rate in patients with K20-positive ICC was lower compared to that of patients with K20-negative ICC, but was not statistically significant. Furthermore, the combined K7/ K20 immunophenotype was identified to be useful for differentiating ICC and metastatic CRC. K20-positive ICC displays specific characteristics with regards to tumor location and histological subtype. Additionally, MUC6 expression in ICC is a good independent prognostic factor, while K20 expression is more often associated with aggressive biological behavior.

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“…Of the nine studies that have examined the prognostic value of MUC1 in CC, all except one have demonstrated a significant correlation between MUC1 expression and decreased survival, both on univariate and multivariate survival analyses (61,62,(101)(102)(103)(104)(105)(106)(107).…”

Section: Muc1mentioning

confidence: 99%

Prognostic molecular markers in cholangiocarcinoma: A systematic review

Briggs

Neal

Mann

et al. 2009

European Journal of Cancer

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The worldwide incidence of cholangiocarcinoma (CC) is steadily rising, the United Kingdom incidence now exceeding 1000 cases per year. It is an aggresive malignancy typified by unresponsiveness to existing chemotherapy and radiotherapy regimes in the vast majority of cases. Surgery offers the only hope of a cure, though postoperative disease recurrence is common, with 5-year survival rates following resection of less then 25%. Developments in molecular techniques and improved understanding of the basis of carcinogenesis in CC has led to examination of the role of biomarkers in predicting poor outcome. This systematic review examines published evidence relating to the prognostic significance of these molecular markers in CC. Of the molecular markers which have been investigated to date p53 mutation, cyclins, proliferation indices, mucins, CA19-9, CRP, and aneuploidy appear to hold significant potential as predictors of outcome in CC. These and other biomarkers may themselves represent novel therapeutic targets for CC.

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Expression of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas: Its relationship with tumor progression and prognosis

Cited by 76 publications

References 35 publications

Expression of MUC1, MUC2, MUC5AC and MUC6 in cholangiocarcinoma: Prognostic impact

Expression of MUC1, MUC2, MUC5AC and MUC6 in cholangiocarcinoma: Prognostic impact

Expression of keratin 20 and its clinicopathological significance in intrahepatic cholangiocarcinoma

Prognostic molecular markers in cholangiocarcinoma: A systematic review

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