PRAME

by Assia Bassarova

Background

Preferentially expressed antigen in melanoma (PRAME) is a tumor associated antigen. It is predominantly expressed in human melanomas and recognized by cytotoxic T-lymphocytes. Coded by the gene with the same name. Belongs to the cancer/testis antigen (CTA) gene family. PRAME can inhibit differentiation and apoptosis mediated by retinoic acid signaling. Considered as a potential target for immunotherapy.

Reactivity in normal tissues

Expressed mainly in testicular germ cells. Low levels of expressions found also in endometrial, ovarian and adrenal gland tissues.

Reactivity in tumors

Expression of PRAME is found in a wide range of different cancers including:

  • Around 90% of malignant melanomas and around 95% of metastatic melanoma,
  • Only 35% of desmoplastic melanomas.
  • 25-30% of benign or atypical Spitzoid lesions.
  • 100% of myxoid and round cell liposarcoma, around 70% of osteosarcoma,
  • 100% squamous cell carcinoma of thymus and only in minority of cases of thymoma.
  • 40% acute myeloid leukemia (AML)  chronic myelogenous leukemia (CML),
  • 30% acute lymphoblastic leukemia (ALL),
  • Weak nuclear expression in cases of lobular and NOS types of breast carcinoma in 25% respectively <35%.
  • The protein is expressed also in minority (<20%) HER-2 positive breast carcinomas, while it is not reported among triple negative and ER-positive cases.
  • Varying frequency of positive staining is also reported in of 40% renal cell carcinoma, non-small cell lung carcinoma (NSCLC) and neuroblastoma.
  • Appears to be be an independent negative prognostic factor for disease-free survival in some solid tumors including breast carcinoma, uveal melanoma,
  • Clear cell sarcoma is reported to give consistently negative negative staining in contrast to malignant melanomas.
  • Only 10-15% of benign melanocytic tumors show positivity in minority of  nuclei but this may be a source of  potential diagnostic pitfall

Staining pattern

Staining pattern is nuclear.

Control tissue

Testis

Application

  • Diagnosis of primary and metastatic melanoma
  • Differential diagnosis squamous cell carcinoma of thymus vs. thymoma
  • Seems to be useful additional marker for myxoid and round cell liposarcoma
  • Differential diagnosis clear cell sarcoma (negative) vs. malignant melanoma (positive)

Selected references

  1. Al-Khadairi G,1 and Decock J.1,2,*Cancer Testis Antigens and Immunotherapy: Where Do We Stand in the Targeting of PRAME?Cancers (Basel). 2019 Jul; 11(7): 984. Published online 2019 Jul 15. doi: 10.3390/cancers11070984 PMCID: PMC6678383 PMID: 31311081
  2. Curigliano G 1, Bagnardi V. 2, Ghioni M 3, et al. Expression of tumor-associated antigens in breast cancer subtypes. Breast. 2020 Feb;49:202-209.  doi: 10.1016/j.breast.2019.12.002. Epub 2019 Dec 12. PMID: 31869767  PMCID: PMC7375652 DOI: 10.1016/j.breast.2019.12.002
  3. Lezcano C. 1, Jungbluth A. J.  1, Nehal K.S. 2, et al. PRAME Expression in Melanocytic Tumors Am J Surg Pathol. 2018 Nov;42(11):1456-1465.  doi:  10.1097/PAS.0000000000001134. ID: 30045064 PMCID: PMC6631376  DOI: 10.1097/PAS.0000000000001134 
  4. Raghavan S.S.1, Wang J.Y.23, Kwok S.2, et al. PRAME expression in melanocytic proliferations with intermediate histopathologic or spitzoid features. J Cutan Pathol. 2020 Dec;47(12):1123-1131.  doi: 10.1111/cup.13818. Epub 2020 Sep 10. PMID: 32700786 DOI: 10.1111/cup.13818
  5. Taniguchi Y. 1, Yoshida M. 2, Saito T 1, et al. Preferentially expressed antigen in melanoma as a novel diagnostic marker differentiating thymic squamous cell carcinoma from thymoma. Sci Rep 2020 Jul 23;10(1):12286.  doi: 10.1038/s41598-020-69260-z. PMID: 32704057 PMCID: PMC7378236 DOI: 10.1038/s41598-020-69260-z