Mesothelin Expression Is a Prognostic Factor in Cholangiocellular Carcinoma

Abstract

Although mesothelin is highly expressed in epithelial mesotheliomas, and also in adenocarcinomas of the ovary and pancreas, the clinical significance of mesothelin in cholangiocellular carcinoma (CC) has not been reported, and its biologic features are largely unknown. In the present study, mesothelin expression was evaluated in 25 patients with CC using a well-characterized mesothelin monoclonal antibody (5B2). A total of 8 of the 25 patients with CC (32%) showed mesothelin immunoreactivity. The 25 patients were divided into 2 groups according to the percentage of tumor cells that were positive for mesothelin expression: negative (n ¼ 17) or focally positive (mesothelin expression evident in less than 50%, n ¼ 4; total, n ¼ 21 for both groups), and positive (mesothelin expression evident in 50% or more, n ¼ 4). The survival periods in both groups were statistically analyzed. The negative/focally positive group showed significantly longer postoperative survival than the positive group (P ¼ 0.006). Also, mesothelin positivity was identified as an independent predictor of short postoperative survival. The present results suggest that mesothelin expression is a prognostic indicator in patients with CC.

Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model

“…Compatible with the findings of Nomura et al7 for human ICC, Msln overexpression in the cholangiocarcinoma cells strongly correlated in our rat model with increasing liver tumor growth and malignant aggressiveness, further suggesting Msln overexpression as being associated with ICC progression. Our results demonstrating increased serum Msln to correlate with increasing tumor size are also in full agreement with the findings of Fukamachi et al,35 who reported an interrelationship between the serum Msln level and tumor size in a rat pancreatic cancer model.…”

“…Notably, in their systematic review and meta‐analysis to investigate the prognostic value of immunohistochemically based biomarkers that have been assessed in patients with resected ICC, Ruys et al13 graded the study of Utispan et al6 on Postn as having a high risk of bias based on defined criteria to evaluate publication bias for biomarkers. Also, in contrast to the findings of Nomura et al,7 Higashi et al14 observed no significant difference in survival on resected ICC patients with Msln‐positive tumors compared with those that were Msln negative. In addition, in a single‐center clinical study involving nine human cases of biliary cancers, median serum Msln was not elevated over that determined for healthy donors 15.…”

“…The ultimate aim is to devise more effective strategies for the clinical management of advanced or recurrent ICC. In this context, the matricellular glycoprotein periostin (Postn) and the glycosylphosphatidylinositol‐anchored cell membrane glycoprotein mesothelin (Msln) have each been independently suggested as having potential as prognostic factors for human ICC 6, 7. Each may also provide opportunities for the development of novel targeted therapies for ICC 8, 9…”

“…Furthermore, 32%‐37% of analyzed cases of human ICCs have been determined to overexpress Msln,7, 9, 12 which was either not detected or only occasionally and weakly seen in HCC9, 12 and not observed in normal adult human liver tissue samples 9. Patients with ICC with resected tumors containing ≥50% Msln‐positive cholangiocarcinoma cells exhibited a significantly shorter postoperative survival than those exhibiting Msln negativity or focal positivity,7 suggesting Msln overexpression to be a prognostic factor in patients undergoing hepatectomy for ICC.…”

Cholangiocarcinoma — evolving concepts and therapeutic strategies

“…Mesothelin, a cell-surface protein expressed in nonmalignant mesothelial cells, is often aberrantly expressed in cholangiocarcinomas, and is associated with advanced-stage and metastatic disease, and unfavourable overall survival 144,145 . Thus, this protein is an attractive target for therapy.…”