Mucin core protein expression in extrahepatic bile duct carcinoma is associated with metastases to the liver and poor prognosis

Takao, Sonshin; Uchikura, Keiichiro; Yonezawa, Suguru; Shinchi, Hiroyuki; Aikou, Takashi

doi:10.1002/(sici)1097-0142(19991115)86:10<1966::aid-cncr13>3.0.co;2-m

Cited by 57 publications

(38 citation statements)

References 43 publications

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“…MUC1 has been reported to be a poor prognostic factor in various human tumors (9)(10)(11)(12)(13)(14)(15)(28)(29)(30). Recently, MUC4 has been reported as a membrane mucin like MUC1 (23).…”

Section: Discussionmentioning

confidence: 99%

MUC4 Is a Novel Prognostic Factor of Extrahepatic Bile Duct Carcinoma

Tamada

Shibahara²,

Higashi³

et al. 2006

Clinical Cancer Research

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Purpose: Many of the patients with extrahepatic bile duct carcinoma (EHBDC) show a poor outcome.We have reported that MUC4 is a novel prognostic factor of pancreatic adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to evaluate the prognostic significance of MUC4 expression in EHBDC. Experimental Design: We examined the expression profile of MUC4 in EHBDC tissues from 70 patients using immunohistochemistry. MUC4 is a membrane mucin like MUC1. In addition, MUC4 is an intramembrane ligand for receptor tyrosine kinase ErbB2 and is related with regulation of p27.We compared the MUC4 expression with MUC1, ErbB2, or p27 expression in EHBDC. Results: MUC4 was expressed in 36 of the 70 patients with EHBDC. There was no significant correlation between the MUC4 expression and MUC1, ErbB2, or p27 expression. The survival of 19 patients with high MUC4 expression (z20% of carcinoma cells stained) was significantly worse than that of the 51 patients with low MUC4 expression (under 20 % of carcinoma cells stained; P = 0.0072). The univariate analysis showed that high MUC4 expression (P = 0.0072), high MUC1 expression (P = 0.0092), histologic grading (P = 0.0029), surgical margin involvement (P = 0.0137), and nodal metastasis (P = 0.0036) were statistically significant risk factors. The backward stepwise multivariate analysis showed that high MUC4 expression (P = 0.0195) and surgical margin involvement (P = 0.0358) were statistically significant independent risk factors. Conclusions: MUC4 expression in EHBDC is a new independent factor for poor prognosis and predicts the outcome of patients with EHBDC.

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“…MUC1 has been reported to be a poor prognostic factor in various human tumors (9)(10)(11)(12)(13)(14)(15)(28)(29)(30). Recently, MUC4 has been reported as a membrane mucin like MUC1 (23).…”

Section: Discussionmentioning

confidence: 99%

MUC4 Is a Novel Prognostic Factor of Extrahepatic Bile Duct Carcinoma

Tamada

Shibahara²,

Higashi³

et al. 2006

Clinical Cancer Research

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“…MUC1 expressed in tumors may function as an anti-adhesion molecule, which inhibits cell-cell adhesion, inducing a release of cells from tumor nests. Thus, MUC1 expression may be related to invasion or metastasis of carcinoma cells [17][18][19] . MUC1 can down-regulate the expression of E-cadherin, which is a calcium-dependent adhesion molecule, functioning in the cellcell adhesion, while the low-expression of E-cadherin increased the invading ability of tumor cells [20][21][22] .…”

Section: Discussionmentioning

confidence: 99%

Expression of MUC1 in esophageal squamous-cell carcinoma and its relationship with prognosis of patients from Linzhou city, a high incidence area of northern China

Song

Gao²,

Yi³

et al. 2003

WJG

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AIM:To further characterize the possible relationship between the molecular changes and prognosis of ESC and to elucidate the possible mechanisms involved. METHODS:114 specimens of ESC were collected from Linzhou city, and all patients were followed up for more than 5 years after resection. Histopathological analysis and immunohistochemical staining (ABC) were employed to detect the alteration of MUC1. RESULTS:The positive immunostaining rate for MUC1 was 79 % (90/114), and the high-expression rate was 63 % (72/114). The mean survival periods (months) of those with high-and low-expression rates of MUC1 were 41 (95 % CI: 35, 47) and 52 (95 % CI: 45, 59), respectively. Patients in the low-expression group obviously survived longer than those in high-expression group, and the difference was significant (P<0.05). The expression of MUC1 protein in the esophageal carcinoma specimens with metastasis was stronger than those without metastasis, the difference was also significant (P<0.05). The stepwise multivariate analysis showed that "differentiation", "expression of MUC1" and "TNM staging" were the most important factors affecting the prognosis of esophageal carcinoma patients (P<0.05). CONCLUSION:A good correlation between the alteration of MUC1 and the regional lymph node metastasis was observed. Furthermore, high-expression of MUC1 was associated with poor prognosis for esophageal cancer patients. These results indicated that MUC1 is a promising biomarker for predicting lymph node metastasis and prognosis in esophageal cancer.

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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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Mucin core protein expression in extrahepatic bile duct carcinoma is associated with metastases to the liver and poor prognosis

Cited by 57 publications

References 43 publications

MUC4 Is a Novel Prognostic Factor of Extrahepatic Bile Duct Carcinoma

MUC4 Is a Novel Prognostic Factor of Extrahepatic Bile Duct Carcinoma

Expression of MUC1 in esophageal squamous-cell carcinoma and its relationship with prognosis of patients from Linzhou city, a high incidence area of northern China

Prognostic molecular markers in cholangiocarcinoma: A systematic review

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