Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Nov 1;46(11):1467-1476.
doi: 10.1097/PAS.0000000000001944. Epub 2022 Aug 16.

PRAME Expression in Cancer. A Systematic Immunohistochemical Study of >5800 Epithelial and Nonepithelial Tumors

Maciej Kaczorowski  1   2 , Małgorzata Chłopek  1 , Anna Kruczak  3 , Janusz Ryś  3 , Jerzy Lasota  1 , Markku Miettinen  1
Affiliations

PRAME Expression in Cancer. A Systematic Immunohistochemical Study of >5800 Epithelial and Nonepithelial Tumors

Maciej Kaczorowski et al. Am J Surg Pathol. .

Abstract

Preferentially expressed antigen in melanoma (PRAME) is considered a useful marker in the differential diagnosis between malignant melanoma and its melanocytic mimics. Recently PRAME expression was documented in nonmelanocytic tumors, but much of the data are based on mRNA studies. This investigation evaluated PRAME expression in the spectrum of normal tissues and >5800 human tumors using immunohistochemistry and EP461 monoclonal antibody. In normal tissues, PRAME was expressed in the testis and proliferative endometrium. In tumors, PRAME was variably expressed in malignancies of different lineages. Among epithelial tumors, >50% of PRAME-positive lesions were found among endometrial carcinomas (82%), uterine serous carcinomas (82%), uterine carcinosarcomas (60%), ovarian clear cell carcinomas (90%), ovarian serous carcinomas (63%), adenoid cystic carcinomas (81%), seminomas (78%), thymic carcinomas (75%), and basal cell carcinomas (62%). In mesenchymal and neuroectodermal malignancies, PRAME was frequently expressed in synovial sarcoma (71%), myxoid liposarcoma (76%), neuroblastoma (61%) and metastatic melanoma (87%). Also, PRAME was consistently expressed in 4 melanomas that lacked all melanoma markers including S100 protein and SOX10 but harbored typical for melanoma BRAF or NRAS driver mutations. However, strong and diffuse PRAME immunoreactivity was seen in many types of nonmelanocytic poorly differentiated carcinomas and sarcomas. Based on this study, PRAME is a relatively unspecific immunohistochemical marker, which limits its use in diagnostic surgical pathology. However, immunohistochemistry is a reliable and unexpensive method useful in detecting PRAME-positive malignancies for potential immunotherapy.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Figures

Figure 1.
Figure 1.
PRAME expression in selected epithelial tumors. A. Strong expression in clear cell ovarian carcinoma. B. Staining in salivary gland adenoid cystic carcinoma present in either epithelial and myoepithelial cells. C. Diffuse immunolabelling in a spermatocytic tumor. D. Clear cell renal cell carcinoma, G3 with weak to moderate intensity of PRAME expression.
Figure 2.
Figure 2.
PRAME expression in poorly differentiated malignancies. A. Poorly differentiated thymic carcinoma. B. Anaplastic thyroid carcinoma with sarcomatoid morphology. C. Poorly differentiated colorectal cancer with unusual morphology metastatic to the brain. D. Dedifferentiated melanoma verified by an NRAS Q61L mutation. The tumor was negative for all melanoma markers, including S100 protein and SOX10.
Figure 3.
Figure 3.
PRAME expression in synovial sarcoma and histologic mimics. A. Diffuse and strong staining was relatively frequent among synovial sarcomas. B. Malignant peripheral nerve sheath tumors were less frequently PRAME-positive and the staining had usually weak or moderate intensity. C. Solitary fibrous tumor is negative. D. One of several solitary fibrous tumor-like tumors that exhibited PRAME expression; these cases were negative for STAT6 and CD34.
Figure 4.
Figure 4.
PRAME expression in small blue round cell tumors. A. Neuroblastoma; diffuse staining was observed in half of positive cases. B. Wilms tumor; diffuse positivity in epithelial structures. C. Desmoplastic small round cell tumor; diffuse, moderately intense immunolabelling. D. Alveolar rhabdomyosarcoma; variable intensity of PRAME expression.
See this image and copyright information in PMC

References

    1. Ikeda H, Lethé B, Lehmann F, et al. Characterization of an Antigen That Is Recognized on a Melanoma Showing Partial HLA Loss by CTL Expressing an NK Inhibitory Receptor. Immunity 1997;6:199–208. - PubMed
    1. Epping MT, Wang L, Edel MJ, et al. The Human Tumor Antigen PRAME Is a Dominant Repressor of Retinoic Acid Receptor Signaling. Cell 2005;122:835–847. - PubMed
    1. Kern CH, Yang M, Liu WS. The PRAME family of cancer testis antigens is essential for germline development and gametogenesis. Biol. Reprod 2021;105:290–304. - PubMed
    1. Figueiredo DLA, Mamede RCM, Proto-Siqueira R, et al. Expression of cancer testis antigens in head and neck squamous cell carcinomas. Head Neck 2006;28:614–619. - PubMed
    1. Szczepanski MJ, Deleo AB, Łuczak M, et al. PRAME expression in head and neck cancer correlates with markers of poor prognosis and might help in selecting candidates for retinoid chemoprevention in pre-malignant lesions. Oral Oncol 2013;49:144–151. - PMC - PubMed

Publication types