Analysis of More than 16,000 Human Tumor and Normal Tissues Identifies Uroplakin 3B as a Useful Diagnostic Marker for Mesothelioma and Normal Mesothelial Cells

Our plain-English summary of Analysis of More than 16,000 Human Tumor and Normal Tissues Identifies Uroplakin 3B as a Useful Diagnostic Marker for Mesothelioma and Normal Mesothelial Cells, by M. Lennartz, D. Atug, S. Dwertmann Rico, et al (Diagnostics, 2022).

The study

• Authors: M. Lennartz, D. Atug, S. Dwertmann Rico, V. Reiswich, F. Viehweger, F. Büscheck, M. Kluth, C. Hube-Magg, A. Hinsch, C. Bernreuther, G. Sauter, E. Burandt, A.H. Marx, T. Krech, R. Simon, S. Minner, T.S. Clauditz, F. Jacobsen, P. Lebok, N. Gorbokon, K. Möller, S. Steurer, C. Fraune
• Journal: Diagnostics
• Published: 2022;12(10)
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Uroplakin 3B (Upk3b) is involved in stabilizing and strengthening the urothelial cell layer of the bladder. Based on RNA expression studies, Upk3b is expressed in a limited number of normal and tumor tissues. The potential use of Upk3b as a diagnostic or prognostic marker in tumor diagnosis has not yet been extensively investigated. A tissue microarray containing 17,693 samples from 151 different tumor types/subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. In normal tissues, Upk3b expression was largely limited to mesothelial cells, urothelial umbrella cells, and amnion cells. In tumor tissues, Upk3b was detectable in only 17 of 151 (11.3%) of tumor types. Upk3b expression was most frequent in mesotheliomas (82.1% of epithelioid and 30.8% of biphasic) and in urothelial tumors of the urinary bladder, where the positivity rate decreased from 61.9% in pTaG2 (low grade) to 58.0% in pTaG3 (high grade) and 14.6% in pT2-4 cancers. Among pT2-4 urothelial carcinomas, Upk3b staining was unrelated to tumor stage, lymph node status, and patient prognosis. Less commonly, Upk3b expression was also seen in Brenner tumors of the ovary (10.8%), as well as in four other subtypes of ovarian cancer (0.9-10.6%). Four additional tumor entities showed a weak to moderate Upk3b positivity in less than 5% of cases. In summary, Upk3b immunohistochemistry is a useful diagnostic tool for the distinction of mesotheliomas from other thoracic tumors and the visualization of normal mesothelial and umbrella cells.

In plain English

This laboratory study, by pathologists in Hamburg, Germany, tested whether staining for a protein called uroplakin 3B (Upk3b) can help identify mesothelioma under the microscope. It did not study asbestos or any other exposure. The authors stained archived tissue samples arranged on tissue microarrays: 608 normal samples covering 76 tissue types, and 17,693 tumors from 151 tumor types, of which 16,185 could be evaluated. In normal tissue, strong staining was seen in mesothelial cells, urothelial umbrella cells and amnion cells. Among all evaluable tumors, 356 of 16,185 (2.2%) stained. Positivity was highest in epithelioid mesotheliomas (82.1% of 28 evaluable). In biphasic mesotheliomas, 30.8% of 52 stained, always only in epithelioid cells. All 184 lung adenocarcinomas were negative. Some urothelial and ovarian tumors also stained. The authors concluded that Upk3b staining offers potential use in distinguishing mesotheliomas from other chest tumors. They noted that staining in ovarian cancers limits its use for peritoneal mesothelioma, and that comparison with established markers is still needed. The main antibody was provided by a company owned by a family member of one author.

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 normal and tumor tissue samples arranged on tissue microarrays
• Who was studied: 608 normal tissue samples (8 donors for each of 76 normal tissue types) and 17,693 primary tumors from 151 tumor types and subtypes. 16,185 tumors were interpretable. Samples came from pathology archives in Hamburg, Osnabrueck and Fuerth, Germany. The mesotheliomas were 40 epithelioid (28 interpretable) and 77 biphasic (52 interpretable). They were listed under tumors of the lung, pleura and thymus, and their site was not otherwise specified.
• Exposure: No asbestos or other exposure was studied. Tissues were stained for the protein Upk3b with the antibody MSVA-736M, and a second antibody (C362) was used to check the normal-tissue findings.
• Main results:
  • 16,185 (91.5%) of the 17,693 tumor samples could be interpreted.
  • In normal tissues, strong Upk3b staining was seen in urothelial umbrella cells, normal mesothelial cells and amnion cells.
  • Across all analyzable tumors, Upk3b staining was found in 356 of 16,185 (2.2%).
  • Epithelioid mesotheliomas had the highest positivity rate of any tumor type (82.1%). Biphasic mesotheliomas were positive in 30.8%, with staining always limited to epithelioid cells. That biphasic rate is lower than the rates Table 1 implies for several non-invasive urothelial carcinoma groups.
  • No Upk3b staining was found in any of 184 lung adenocarcinomas.
  • Staining in more than 80% of tumor cells at moderate or strong intensity was largely limited to mesotheliomas (11.1 to 42.9%).
  • Upk3b staining also occurred in Brenner tumors of the ovary (10.8%) and in four other subtypes of ovarian cancer (0.9 to 10.6%).
  • In non-invasive bladder urothelial tumors, the positivity rate fell from 61.9% in pTaG2 (low grade) to 58.0% in pTaG3 (high grade) (p less than 0.05). It was 14.6% in muscle-invasive urothelial carcinomas.
  • The authors reported that, within muscle-invasive urothelial cancers, Upk3b staining was unrelated to tumor stage, lymph node status and patient prognosis.
• The authors' conclusion: The authors concluded that the pattern of Upk3b expression offers potential diagnostic uses, including distinguishing mesotheliomas from other primary or metastatic chest tumors and showing normal mesothelial and umbrella cells.
• Limitations the authors state:
  • Upk3b-positive ovarian cancer cells limit the use of Upk3b staining for diagnosing malignant mesothelioma of the peritoneum.
  • Further studies are needed to compare Upk3b staining with markers already in use.
  • Upk3b may be of limited use for telling urothelial cancer apart from other tumors, because most muscle-invasive urothelial cancers were negative.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Mesothelial Cells, Immunohistochemistry, Epithelioid, Biphasic Mesothelioma, Carcinoma, Prognosis, Ovarian Cancer.

Related studies

• 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)
• Cytokeratin 5 and cytokeratin 6 expressions are unconnected in normal and cancerous tissues and have separate diagnostic implications — C. Völkel, N. De Wispelaere, et al. (2022)
• Glutathione peroxidase 2 expression in human tumors: a tissue microarray study on 18,555 tumors — V. Chirico, N. Jahn, et al. (2026)
• 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 Diagnostics, or return to medical research.