Mesothelin expression is a prognostic factor in cholangiocellular carcinoma

Our plain-English summary of Mesothelin expression is a prognostic factor in cholangiocellular carcinoma, by R. Nomura, H. Fujii, M. Abe, et al (International Surgery, 2013).

The study

• Authors: R. Nomura, H. Fujii, M. Abe, H. Sugo, Y. Ishizaki, S. Kawasaki, O. Hino
• Journal: International Surgery
• Published: 2013;98(2):164-9
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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 = 17) or focally positive (mesothelin expression evident in less than 50%, n = 4; total, n = 21 for both groups), and positive (mesothelin expression evident in 50% or more, n = 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 = 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.

In plain English

This study from Juntendo University in Tokyo, Japan, examined a protein called mesothelin in tumors from 25 patients whose cholangiocellular carcinoma (a cancer of the bile ducts) had been completely removed by liver surgery at the authors' institute between 1987 and 2003. The study did not examine asbestos exposure. The authors stained tumor tissue with an antibody (5B2) that detects mesothelin. Eight of the 25 patients (32%) showed mesothelin. In 4 it appeared in fewer than half of the tumor cells ("focally positive"), and in 4 it appeared in more than half ("positive"). The other 17 were negative. The 4 positive patients had significantly shorter survival after surgery than the 21 negative or focally positive patients (P = 0.006). In an analysis that also included blood vessel invasion and lymph node spread, mesothelin positivity was the only independent predictor of shorter survival (hazard ratio 4.67, 95% confidence interval 1.256 to 17.352). The authors concluded that mesothelin expression is a prognostic indicator in this cancer. They noted it remains unclear whether mesothelin causes the cancer's malignant character or results from it.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of stored surgical tumor tissue stained for mesothelin (immunohistochemistry), with survival analysis (Kaplan-Meier, log-rank test, Cox proportional hazards model)
• Who was studied: 25 patients (17 men, 8 women, aged 37 to 77, mean 58.0 years) whose cholangiocellular carcinoma was completely resected by hepatectomy at Juntendo University, Tokyo, Japan, between 1987 and 2003. Of 30 operated patients, 3 absolutely noncurative patients and 2 with unclear prognosis were excluded. No hilar cholangiocarcinoma (Klatskin tumor) cases were included.
• Main results:
  • 8 of the 25 patients (32%) showed mesothelin immunoreactivity. 4 were focally positive (less than 50% of tumor cells), 4 were positive (more than 50%), and 17 were negative.
  • 5 of the 8 patients with mesothelin immunoreactivity (62.5%) had stage IV disease.
  • The mesothelin-positive group (n = 4) had significantly shorter postoperative survival than the negative or focally positive group (n = 21); P = 0.006.
  • In univariate analysis, patients with vascular invasion had significantly shorter survival than those without (P = 0.028). Patients with pathologically evident lymph node metastasis also had shorter survival than those without (P = 0.012).
  • In multivariate Cox analysis, mesothelin positivity was the sole predictor of short postoperative survival: hazard ratio 4.67, 95% CI 1.256 to 17.352, P = 0.021. Vascular invasion (hazard ratio 1.44, 95% CI 0.344 to 6.002, P = 0.620) and pathologic node classification (hazard ratio 2.52, 95% CI 0.897 to 7.098, P = 0.080) were not significant.
• The authors' conclusion: The authors concluded that mesothelin expression is a prognostic indicator in patients with cholangiocellular carcinoma, and suggested that mesothelin may exert some effect on the development of this cancer.
• Limitations the authors state:
  • The authors state it is unclear whether mesothelin expression is a reason for the malignant character of the cancer or a result of it.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Carcinoma, Mesothelioma, Adenocarcinoma, Monoclonal Antibody.

Related studies

• Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis — G. Brandi, S. Di Girolamo, et al. (2013)
• New insights into the molecular pathogenesis of intrahepatic cholangiocarcinoma — T. Patel (2014)
• Asbestos exposure as an additional risk factor for small duct intrahepatic cholangiocarcinoma: a pilot study — F. Vasuri, M. Deserti, et al. (2023)
• Mesothelin-related predictive and prognostic factors in malignant mesothelioma: a nested case-control study — O.D. Roe, J. Creaney, et al. (2008)
• The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor — K. Hollevoet, K. Nackaerts, et al. (2012)
• Exposure to Asbestos and Increased Intrahepatic Cholangiocarcinoma Risk: Growing Evidences of a Putative Causal Link — G. Brandi, K. Straif, et al. (2022)

Browse return to medical research.