Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors

Our plain-English summary of Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors, by S. Weidemann, P. Gagelmann, N. Gorbokon, et al (Biomedicines, 2021).

The study

• Authors: S. Weidemann, P. Gagelmann, N. Gorbokon, M. Lennartz, A. Menz, A.M. Luebke, M. Kluth, C. Hube-Magg, N.C. Blessin, C. Fraune, K. Möller, C. Bernreuther, P. Lebok, T.S. Clauditz, F. Jacobsen, J.R. Izbicki, K. Jansen, G. Sauter, R. Uhlig, W. Wilczak, S. Steurer, S. Minner, E. Burandt, R.H. Krech, D. Dum, T. Krech, A.H. Marx, R. Simon
• Journal: Biomedicines
• Published: 2021;9(4)
• Cited by: 91 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelin (MSLN) represents an attractive molecule for targeted cancer therapies. To identify tumors that might benefit from such therapies, tissue microarrays including 15,050 tumors from 122 different tumor types and 76 healthy organs were analyzed for MSLN expression by immunohistochemistry. Sixty-six (54%) tumor types showed at least occasional weak staining, including 50 (41%) tumor types with at least one strongly positive sample. Highest prevalence of MSLN positivity had ovarian carcinomas (serous 97%, clear cell 83%, endometrioid 77%, mucinous 71%, carcinosarcoma 65%), pancreatic adenocarcinoma (ductal 75%, ampullary 81%), endometrial carcinomas (clear cell 71%, serous 57%, carcinosarcoma 50%, endometrioid 45%), malignant mesothelioma (69%), and adenocarcinoma of the lung (55%). MSLN was rare in cancers of the breast (7% of 1138), kidney (7% of 807), thyroid gland (1% of 638), soft tissues (0.3% of 931), and prostate (0 of 481). High expression was linked to advanced pathological tumor (pT) stage (p < 0.0001) and metastasis (p < 0.0001) in 1619 colorectal adenocarcinomas, but unrelated to parameters of malignancy in 1072 breast-, 386 ovarian-, 174 lung-, 757 kidney-, 171 endometrial-, 373 gastric-, and 925 bladder carcinomas. In summary, numerous important cancer types with high-level MSLN expression might benefit from future anti-MSLN therapies, but MSLN's prognostic relevance appears to be limited.

In plain English

This laboratory study did not examine asbestos exposure. The authors measured the protein mesothelin in archived tumor tissue by immunohistochemistry on tissue microarrays, which hold many small tissue samples on one slide. They also tested 76 normal tissue types. Of 15,050 tumors from 122 tumor types, 12,679 could be assessed. Mesothelin staining was seen in 2413 (19.0%) of the assessable tumors. The highest rates were in subtypes of ovarian cancer (65% to 97%), endometrial cancer (45% to 71%), pancreatic adenocarcinoma (75% and 81%), malignant mesothelioma (69%) and lung adenocarcinoma (55%). Among mesotheliomas, 64.0% of 25 epitheloid and 70.8% of 65 other-type tumors were positive. Staining was rare or absent in breast, kidney, thyroid, soft tissue and prostate tumors. In 1619 colorectal adenocarcinomas, staining was linked to tumor stage and lymph node status (p less than 0.0001 each). Staining was not related to overall survival in the bladder, breast and kidney cancers tested. The authors judged cancers with 40% or higher positivity the best candidates for anti-mesothelin therapy. They also said their rates are specific to their own reagents and protocol.

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: Laboratory immunohistochemistry study of archived tumor and normal tissues on tissue microarrays, with some comparison to tumor stage, grade and survival data
• Who was studied: 15,050 primary tumors from 122 tumor types and subtypes (12,679 interpretable), plus a normal-tissue array of 76 tissue types with 8 donors each. Samples came from pathology archives in Hamburg, Osnabrueck and Fuerth, Germany. Collection dates are not stated.
• Exposure: No asbestos exposure was studied. The factor measured was mesothelin (MSLN) protein staining in tissue, detected with the mouse monoclonal antibody MSVA-235.
• Main results:
  • Of 12,679 analyzable tumors, 2413 (19.0%) showed MSLN staining: 8.0% weak, 3.4% moderate and 7.6% strong
  • The highest positivity rates were in ovarian carcinoma subtypes (65% to 97%), endometrial carcinoma subtypes (45% to 71%), pancreatic adenocarcinoma (75% and 81%), malignant mesothelioma (69%) and lung adenocarcinoma (55%)
  • Epitheloid mesothelioma: 25 of 39 samples analyzable; 64.0% positive, including 48.0% strong
  • Mesothelioma, other types: 65 of 76 samples analyzable; 70.8% positive, including 55.4% strong
  • Positivity was rare or absent in breast tumor subtypes (for example 6.6% of invasive no special type), renal cell tumors, thyroid carcinomas (0% to 1.4%), soft tissue tumors (0.3%) and prostate adenocarcinomas (0%)
  • In 1619 colorectal adenocarcinomas, MSLN staining was associated with pT stage and pN status (p < 0.0001 each)
  • MSLN staining was not related to overall survival in 227 bladder carcinomas (p = 0.3302), 593 invasive breast carcinomas of no special type (p = 0.0976) and 502 clear cell renal cell carcinomas (p = 0.3144). The authors said the lack of associations in several cancer types argues against a major prognostic role.
  • MSLN positivity was associated with RAS mutations in colorectal carcinomas (p = 0.0010) and with triple negative status in invasive breast carcinomas of no special type (p < 0.0001)
  • Across squamous cell carcinomas, MSLN positivity was 58.1% in 93 HPV positive cases versus 43.3% in 427 HPV negative cases (p = 0.0098)
• The authors' conclusion: The authors concluded that cancers with a positivity rate of 40% or higher in their study (including ovarian, endometrial and pancreatic cancers and malignant mesothelioma) appear to be the best candidates for anti-MSLN therapy. They also concluded that MSLN's prognostic impact appears low outside colon cancer.
• Limitations the authors state:
  • The small tissue spots (0.6 mm) risk missing relevant parts of heterogeneous tumors.
  • The positivity rates are specific to the antibody and protocol used in the authors' laboratory.
  • No data on previous therapies were available.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Immunohistochemistry, Carcinoma, Adenocarcinoma, Mesothelioma, Metastasis.

Related studies

• Reduced occludin expression is related to unfavorable tumor phenotype and poor prognosis in many different tumor types: A tissue microarray study on 16,870 tumors — S. Büyücek, F. Viehweger, et al. (2025)
• Glutathione peroxidase 2 expression in human tumors: a tissue microarray study on 18,555 tumors — V. Chirico, N. Jahn, et al. (2026)
• Stimulator of Interferon Genes Protein (STING) Expression in Cancer Cells: A Tissue Microarray Study Evaluating More than 18,000 Tumors from 139 Different Tumor Entities — A. Menz, J. Zerneke, et al. (2024)
• Expression of Annexin A4 in Cancer: A Tissue Microarray Study Involving More than 17,600 Cancers from 148 Tumor Entities — C. Völkel, N. Malas, et al. (2026)
• Prevalence of S-methyl-5'-thioadenosine Phosphorylase (MTAP) Deficiency in Human Cancer: A Tissue Microarray Study on 13,067 Tumors From 149 Different Tumor Types — N. Gorbokon, N. Wößner, et al. (2024)
• Prevalence of heterozygous and homozygous 9p21 deletions in human cancer: a tissue microarray study on 4,999 tumors from 125 different tumor types — N. Gorbokon, K. Teljuk, et al. (2026)

Browse more research in Biomedicines, or return to medical research.