Cancer antigen profiling for malignant pleural mesothelioma immunotherapy: expression and coexpression of mesothelin, cancer antigen 125, and Wilms tumor 1

Our plain-English summary of Cancer antigen profiling for malignant pleural mesothelioma immunotherapy: expression and coexpression of mesothelin, cancer antigen 125, and Wilms tumor 1, by T. Eguchi, K. Kadota, M. Mayor, et al (Oncotarget, 2017).

The study

• Authors: T. Eguchi, K. Kadota, M. Mayor, M.G. Zauderer, A. Rimner, V.W. Rusch, W.D. Travis, M. Sadelain, P.S. Adusumilli
• Journal: Oncotarget
• Published: 2017;8(44):77872-77882
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: To develop cancer antigen-targeted immunotherapeutic strategies for malignant pleural mesothelioma (MPM), we investigated the individual and coexpressions of the cancer-associated antigens mesothelin (MSLN), cancer antigen 125 (CA125), and Wilms tumor 1 (WT1) in both epithelioid and non-epithelioid MPM.

Methods: All available hematoxylin and eosin-stained slides from patients who were diagnosed with MPM (1989-2010) were reviewed. We constructed tissue microarrays from 283 patients (epithelioid = 234; non-epithelioid = 49). Intensity and distribution for each antigen were assessed by immunohistochemistry.

Results: Positive expression of MSLN, CA125, and WT1 were demonstrated in 93%, 75%, and 97% of epithelioid MPM cases, and 57%, 33%, and 98% of non-epithelioid MPM cases, respectively. Triple- and double-positive antigen coexpressions were demonstrated in 72% and 23% of epithelioid MPM cases and 29% and 33% of non-epithelioid MPM cases, respectively. Complete absence of expression for all three antigens was demonstrated in <2% of MPM cases. More than two-thirds of MPM cases had ≥50% distribution of MSLN-positive cells and, among the remaining third, half had ≥50% distribution of WT1-positive cells. CA125/MSLN coexpression was observed in more than two-thirds of epithelioid MPM cases and one-third of non-epithelioid MPM cases.

Conclusion: A limited number of cancer-associated antigens can target almost all MPM tumors for immunotherapy.

In plain English

This retrospective study examined tumor tissue from 283 malignant pleural mesothelioma patients diagnosed at Memorial Sloan Kettering Cancer Center, 1989 to 2010. Of these, 234 were epithelioid and 49 non-epithelioid (26 biphasic, 23 sarcomatoid). The authors stained small tissue samples for three possible immunotherapy targets: mesothelin, cancer antigen 125 (CA125) and Wilms tumor 1 (WT1). Records listed asbestos exposure for 42% of epithelioid and 53% of non-epithelioid patients. Among evaluable epithelioid cases, mesothelin was found in 215 of 230 (93%), CA125 in 169 of 226 (75%) and WT1 in 220 of 226 (97%). In the 49 non-epithelioid cases the figures were 57%, 33% and 98%. Of 220 epithelioid cases evaluated for all three, 158 (72%) showed all three, as did 14 of 49 (29%) non-epithelioid cases. None of the three appeared in 2 of 220 epithelioid and 1 of 49 non-epithelioid cases. Of 269 patients analyzed, 73% had mesothelin in at least half of tumor cells. The authors concluded the results support personalized immunotherapy targeting these three antigens. They noted the small samples might miss tumors that stain only in patches.

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 archived tumor tissue, using tissue microarrays and immunohistochemical staining
• Who was studied: 283 patients with malignant pleural mesothelioma diagnosed at Memorial Sloan Kettering Cancer Center, New York, 1989 to 2010, who had tumor blocks available. They were drawn from 620 patients first reviewed. The 283 comprised 234 epithelioid (39 of them pleomorphic), 26 biphasic and 23 sarcomatoid cases.
• Exposure: The study measured tumor expression of three proteins (mesothelin, CA125, WT1); it did not study asbestos exposure. Patient records listed asbestos exposure as positive for 42% of epithelioid patients (Table 1: 97 of 234, 41.5%) and 53% of non-epithelioid patients (26 of 49, 53.1%). Exposure was recorded as unknown for 28.6% and 32.7% respectively. No fiber types are given.
• Main results:
  • Epithelioid cases: mesothelin was evaluated in 230 cases and was positive in 93% (215 of 230). CA125 was evaluated in 226 cases and was positive in 75% (169 of 226). WT1 was evaluated in 226 cases and was positive in 97% (220 of 226).
  • Non-epithelioid (biphasic or sarcomatoid) cases, all 49 evaluated: mesothelin was positive in 57% (28 of 49), CA125 in 33% (16 of 49) and WT1 in 98% (48 of 49).
  • All three antigens were evaluated together in 220 epithelioid and 49 non-epithelioid cases. All three were present in 72% of epithelioid cases (158 of 220) and 29% of non-epithelioid cases (14 of 49). Exactly two were present in 23% of epithelioid cases (51 of 220) and 33% of non-epithelioid cases (16 of 49).
  • None of the three antigens was found in 1% of epithelioid cases (2 of 220) and 2% of non-epithelioid cases (1 of 49).
  • Mesothelin and CA125 were present together in 73% of epithelioid cases (161 of 220) and 29% of non-epithelioid cases (14 of 49).
  • Of all 269 patients analyzed, 197 (73%) had mesothelin in 50% or more of tumor cells. Another 36 (13%) had WT1 in 50% or more of tumor cells without that level of mesothelin.
  • The share of patients with mesothelin in 50% or more of tumor cells varied by subtype: 161 of 185 (87%) non-pleomorphic epithelioid, 24 of 35 (69%) pleomorphic epithelioid, 9 of 26 (35%) biphasic and 3 of 23 (13%) sarcomatoid.
• The authors' conclusion: The authors concluded that the results provide a rationale for developing personalized immunotherapy for pleural mesothelioma patients that targets mesothelin, CA125 and WT1.
• Limitations the authors state:
  • The tissue microarray, built from small cores of tissue, may fail to identify tumors that are only focally positive on whole-tissue staining. The authors used six cores from different areas of each tumor. They expected that results would not change significantly with whole blocks.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Immunotherapy, Mesothelin, Wilms Tumor 1 (WT-1), Epithelioid, Non-epithelioid, Immunohistochemistry.

Related studies

• Glypican-3 expression in Wilms tumor and hepatoblastoma — J.A. Toretsky, N.L. Zitomersky, et al. (2001)
• Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin-like growth factor 2 expression — A.W. Langerak, K.A. Williamson, et al. (1995)
• Expression of Wilms' tumor gene (WT1) is associated with survival in malignant pleural mesothelioma — S. Cedrés, M.A. Montero, et al. (2014)
• Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies — G.L. Beatty, A.R. Haas, et al. (2014)
• Development of Highly Effective Anti-Mesothelin hYP218 Chimeric Antigen Receptor T Cells With Increased Tumor Infiltration and Persistence for Treating Solid Tumors — S. Tomar, J. Zhang, et al. (2022)
• Serum soluble mesothelin-related protein (SMRP) and fibulin-3 levels correlate with baseline malignant pleural mesothelioma (MPM) tumor volumes but are not useful as biomarkers of response in an immunotherapy trial — S.I. Katz, L. Roshkovan, et al. (2021)

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