Stains & molecular markers
PRAME


Minor changes: 12 May 2021

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PubMed Search: PRAME [TI] pathology

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Cite this page: Lezcano C, Jungbluth AA, Busam KJ. PRAME. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsPRAME.html. Accessed June 20th, 2021.
Definition / general
  • PRAME: preferentially expressed antigen in melanoma (Immunity 1997;6:199)
  • Cancer testis antigen expressed by melanoma and other malignant neoplasms with expression in normal tissue largely restricted to testis (Immunity 1997;6:199)
Essential features
  • Diffusely positive in most melanomas
  • Usually negative or nondiffuse / focal immunoreactivity in nevi, other benign neoplasms and most normal adult tissue (except for testis and a few other tissues which express PRAME)
  • Other malignant tumors, including certain sarcomas, carcinomas and hematolymphoid neoplasms, can show variable extent of PRAME staining in subsets of cases
Terminology
  • Less frequently known as MAPE (melanoma antigen preferentially expressed in tumors) and OIP4 (Opa interacting protein 4) (Mol Cancer 2010;9:226)
Pathophysiology
  • PRAME is a cancer testis antigen that was first identified by autologous T cell epitope cloning in a patient with metastatic cutaneous melanoma (Immunity 1997;6:199)
  • Belongs to family of non X cancer testis antigens, mapping to autosome (chromosome 22) versus classical cancer testis antigens, such as MAGE-A, NY-ESO-1, mapping to chromosome X (Nat Rev Cancer 2005;5:615)
  • Expressed in most cutaneous and ocular melanomas but also in nonmelanocytic malignant tumors, including some carcinomas, leukemias, lymphomas and sarcomas (Immunity 1997;6:199, Int J Surg Pathol 2021 Apr 2 [Epub ahead of print])
  • Most benign adult tissue shows low or absent PRAME mRNA expression, except for testis (high level expression), ovary, placenta, adrenals and endometrium (Immunity 1997;6:199)
  • PRAME acts as a repressor of the retinoic acid receptor (RAR) signaling pathway (Cell 2005;122:835)
Interpretation
Uses by pathologists
Prognostic factors
  • PRAME mRNA expression level has been identified as a biomarker for metastatic risk stratification of uveal melanomas and is part of a 12 gene expression prognostic assay (Clin Cancer Res 2016;22:1234, Oncotarget 2016;7:59209)
  • Possible prognostic implications of PRAME expression in other tumor types remain under study
Microscopic (histologic) description
  • PRAME expression is characterized as diffuse when positive nuclear staining is present in over 75% of tumor cells (Am J Surg Pathol 2018;42:1456)
  • Immunohistochemistry for PRAME can be combined with MelanA in a dual PRAME / MelanA immunostain (e.g. for easier assessment of small melanocytic deposits in lymph nodes) (Am J Surg Pathol 2020;44:503)
Microscopic (histologic) images

Contributed by Cecilia Lezcano, M.D.
PRAME in normal testis

PRAME in normal testis

Primary cutaneous melanoma

Primary cutaneous melanoma

PRAME in primary cutaneous melanoma

PRAME in primary cutaneous melanoma

Melanoma metastasis

Melanoma metastasis


PRAME positive melanoma metastasis RAME positive melanoma metastasis

PRAME positive melanoma metastasis

Nevus

Nevus

PRAME immunostain in nevus

PRAME immunostain in nevus

Positive staining - normal
Positive staining - disease
Negative staining
Sample pathology report
  • Skin, temple, shave:
    • Melanoma in situ (see comment)
    • Comment: Sections show a lentiginous intraepidermal proliferation of atypical melanocytes with occasional nests, multifocal pagetoid spread and diffuse immunoreactivity for PRAME, which is consistent with this diagnosis.
Board review style question #1
Which of the following statements regarding PRAME immunohistochemistry is correct?

  1. All melanomas are positive for PRAME
  2. Benign nevi never show immunoreactivity for PRAME
  3. Diffuse nuclear immunoreactivity for PRAME is seen in a majority of melanomas
  4. Melanoma is the only malignant neoplasm that expresses PRAME
Board review style answer #1
C. Diffuse nuclear immunoreactivity for PRAME is seen in the majority of melanomas (both primary and metastatic). Answer A is incorrect because some primary and metastatic melanomas can be completely negative for PRAME or show only focal expression. Answer B is incorrect because nevi can occasionally show staining for PRAME, usually in a nondiffuse pattern. Answer D is incorrect because the majority of synovial sarcomas and myxoid liposarcomas diffusely express PRAME. Other tumors, including carcinomas of various origins, can also show variable extent of staining for PRAME.

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Reference: PRAME
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