Immunohistochemical Detection of Cancer-Testis Antigen PRAME

Our plain-English summary of Immunohistochemical Detection of Cancer-Testis Antigen PRAME, by C. Lezcano, A.M. Müller, D. Frosina, et al (International Journal of Surgical Pathology, 2021).

The study

• Authors: C. Lezcano, A.M. Müller, D. Frosina, E. Hernandez, J.A. Geronimo, K.J. Busam, A.A. Jungbluth
• Journal: International Journal of Surgical Pathology
• Published: 2021;29(8):826-835
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Cancer-testis (CT) antigens were identified by their ability to elicit T- or B-cell immune responses in the autologous host. They are typically expressed in a wide variety of neoplasms and in normal adult tissues are restricted to testicular germ cells. PReferentially expressed Antigen of Melanoma (PRAME) is a member of the family of nonclassical CT antigens being expressed in a few other normal tissues besides testis. Interestingly, knowledge about the protein expression of many CT antigens is still incomplete due to the limited availability of reagents for their immunohistochemical detection. Here, we tested several commercially available serological reagents and identified a monoclonal antibody suitable for the immunohistochemical detection of PRAME in formalin-fixed paraffin-embedded specimens. We also tested a wide array of normal and neoplastic tissues. PRAME protein expression in normal tissues is congruent with original molecular data being present in the testis, and at low levels in the endometrium, adrenal cortex, and adult as well as fetal ovary. In tumors, there is diffuse PRAME immunoreactivity in most metastatic melanomas, myxoid liposarcomas, and synovial sarcomas. Other neoplasms such as seminomas and carcinomas of various origins including endometrial, serous ovarian, mammary ductal, lung, and renal showed an intermediate proportion of cases and variable extent of tumor cells positive for PRAME protein expression. As seen with other CT antigens, hepatocellular and colorectal carcinoma, Leydig cell tumors, mesothelioma, and leiomyosarcoma are poor expressers of PRAME.

In plain English

This laboratory study, from Memorial Sloan Kettering Cancer Center in New York, tested commercially available antibodies for detecting a protein called PRAME in stored, archived tissue samples. It did not study asbestos or any exposure. The best staining came from one antibody, EPR20330, which the authors then checked against cell lines with known PRAME levels. In normal tissues, staining was seen in testicular germ cells and, less often, in endometrium, adrenal cortex (1 of 6 samples) and ovary. Among 258 malignant tumors, PRAME staining was found in 37 of 40 metastatic melanomas, all 5 myxoid liposarcomas, 14 of 15 synovial sarcomas and 14 of 15 seminomas. Several carcinomas showed intermediate rates. None of the 10 mesotheliomas tested showed PRAME staining. The article does not say whether these were pleural or peritoneal. The authors called their tumor analysis an initial study with a limited number of cases. They concluded that PRAME is frequently and homogeneously expressed in a wide variety of tumors.

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: testing of commercial anti-PRAME antibodies on cell lines and on archived normal and tumor tissue
• Who was studied: Archived formalin-fixed paraffin-embedded normal and tumor tissue from the Department of Pathology archives of Memorial Sloan Kettering Cancer Center (New York), including 258 malignant tumors of 19 types (among them 10 mesotheliomas), plus 7 cell lines
• Exposure: No asbestos or other exposure was studied; the study examined staining of tissues with anti-PRAME antibodies
• Main results:
  • Of the antibodies tested, EPR20330 gave the best staining and was used for all further analysis
  • Normal testis: staining of germ cells, most prominent in cells of early spermatogenesis (5 of 5 testis samples positive in Table 1)
  • Normal adrenal gland: 1 of 6 samples showed focal staining, in the cortex only; most proliferative-phase endometrium samples were positive
  • Metastatic melanoma: 37 of 40 cases (93%) positive, of which 35 of 37 showed staining in more than 75% of tumor cells
  • Myxoid liposarcoma: 5 of 5 positive; synovial sarcoma: 93% (14 of 15 in Table 2) with diffuse staining
  • Seminoma: 93% positive (14 of 15 in Table 2)
  • Endometrial carcinoma 100% (10 of 10), invasive ductal breast carcinoma 47% (7 of 15) and serous ovarian carcinoma 65% (13 of 20) showed some PRAME staining
  • Non-small cell lung carcinoma: 45% of squamous cell carcinomas (9 of 20) and 30% of adenocarcinomas (3 of 10) positive
  • Colorectal carcinoma 10% (2 of 20) and hepatocellular carcinoma 15% (3 of 20) positive
  • Mesothelioma: 0 of 10 cases positive (Table 2); Leydig cell tumors (0 of 5) and gastrointestinal stromal tumors (1 of 10) also showed little to no staining
• The authors' conclusion: The authors concluded that antibody EPR20330 is specific for PRAME in archival specimens. They also concluded that, besides melanoma, PRAME is frequently and homogeneously expressed in a wide variety of tumors, which they described as potential targets for PRAME-based immunotherapy.
• Limitations the authors state:
  • The authors studied a wide variety but a limited number of tumors
  • The authors described the tumor analysis as an initial study; links between PRAME and clinical features were left to future studies

Topics

Medical terms in this study, explained in our Lexicon: Neoplasm, Monoclonal Antibody, Synovial Sarcoma, Carcinoma, Mesothelioma.

Related studies

• Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions — G. Salama, M. Miédougé, et al. (1998)
• Monoclonal antibody SM047 as an immunohistochemical marker of ovarian adenocarcinoma — W.G. McCluggage, P. Maxwell, et al. (2001)
• Distribution of the carbohydrate antigens, DU-PAN-2 and CA19-9, in tumors of the lung — G. Ohshio, K. Yamaki, et al. (1995)
• A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma — J. Lai, Z. Zhou, et al. (2016)
• Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis — R. Carella, G. Deleonardi, et al. (2001)
• Immunohistochemical Evaluation of Minichromosome Maintenance Protein 7 (MCM7), Topoisomerase IIα, and Ki-67 in Diffuse Malignant Peritoneal Mesothelioma Patients Using Tissue Microarray — M. Deraco, A. Cabras, et al. (2015)

Browse more research in International Journal of Surgical Pathology, or return to medical research.