PMID- 36804828 OWN - NLM STAT- MEDLINE DCOM- 20230403 LR - 20231213 IS - 1532-8392 (Electronic) IS - 0046-8177 (Linking) VI - 134 DP - 2023 Apr TI - PRAME expression by immunohistochemistry and reverse transcription quantitative PCR in conjunctival melanocytic lesions-a comprehensive clinicopathologic study of 202 cases and correlation of cytogenetics with PRAME expression in challenging conjunctival melanocytic lesions. PG - 1-18 LID - S0046-8177(23)00030-8 [pii] LID - 10.1016/j.humpath.2023.02.002 [doi] AB - This study examined PRAME (preferentially expressed antigen in melanoma) expression by immunohistochemistry and reverse transcription quantitative PCR (RT-qPCR) in 202 histologically unequivocal conjunctival melanocytic lesions: 76 nevi, 29 benign melanoses, 25 low-grade conjunctival intraepithelial melanocytic lesions (LGCMIL), 26 high-grade conjunctival melanocytic intraepithelial lesions/in-situ melanoma (HGCMIL), and 46 invasive melanomas. PRAME score 0 was seen in 96% of nevi (73/76), 96% of benign melanoses (28/29), and 88% of LGCMIL (22/25). PRAME score 4 was seen in 50% HGCMIL (13/26) and 76% invasive melanomas (35/46). PRAME score 4 had a sensitivity of 50% and specificity of 100% in differentiating between HGCMIL and benign melanosis/LGCMIL. PRAME score 4 had a sensitivity of 76% and specificity of 100% in differentiating between melanoma and nevi. Relative quantification of PRAME mRNA expression by RT-qPCR was performed on 49 cases (24%): 17 nevi, 3 benign melanoses, 5 LGCMIL, 9 HGCMIL, and 15 invasive melanomas. The analysis generated two distinct groupings with 'high' relative PRAME expression for the HGCMIL and invasive melanoma and 'low/zero' expression for nevi, benign melanosis, and LGCMIL. Thirty-three challenging conjunctival melanocytic lesions that had previous fluorescence in situ hybridization (FISH) analysis were studied: 18 nevi, 12 melanomas in a nevus, 2 nevoid melanomas, and 1 in-situ melanoma. All nevi (100%) showed concordance between negative FISH and PRAME (scores 0-3). Four of 13 melanomas (31%; in-situ, invasive, isolated, and in association with nevus) showed concordance between positive FISH and PRAME score 4. In conclusion, PRAME score 4 has 100% specificity for the diagnosis of HGCMIL and melanoma. PRAME is limited in its sensitivity in the evaluation of challenging melanocytic lesions. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Mudhar, Hardeep Singh AU - Mudhar HS AD - National Specialist Ophthalmic Pathology Service (NSOPS), Dept of Histopathology, E-Floor, Royal Hallamshire Hospital, Sheffield S10 2JF, England, UK. Electronic address: hardeep.mudhar@nhs.net. FAU - Milman, Tatyana AU - Milman T AD - Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: tatyana.milman@gmail.com. FAU - Stevenson, Sarah AU - Stevenson S AD - Sheffield Diagnostic Genetics Service, Sheffield Children's Hospital, Sheffield S10 2TH, England, UK; The University of Manchester, Manchester M13 9PL, England, UK. Electronic address: sarah.stevenson11@nhs.net. FAU - Watson, Mark AU - Watson M AD - Sheffield Diagnostic Genetics Service, Sheffield Children's Hospital, Sheffield S10 2TH, England, UK. Electronic address: mark.watson6@nhs.net. FAU - Kim, Julie AU - Kim J AD - Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: Julie.Kim@jefferson.edu. FAU - Magan, Tejal AU - Magan T AD - Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: tejal.magan@nhs.net. FAU - Salvi, Sachin M AU - Salvi SM AD - Sheffield Ocular Oncology Service, Dept of Ophthalmology, A Floor, Royal Hallamshire Hospital, Sheffield S10 2JF, UK. Electronic address: sachin.salvi@nhs.net. FAU - Harley, Umiya AU - Harley U AD - Sheffield Ocular Oncology Service, Dept of Ophthalmology, A Floor, Royal Hallamshire Hospital, Sheffield S10 2JF, UK. Electronic address: umiya.harley@nhs.net. FAU - Lally, Sarah E AU - Lally SE AD - Ocular Oncology Service, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: saralally1@yahoo.com. FAU - Shields, Carol L AU - Shields CL AD - Ocular Oncology Service, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: carolshields@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230216 PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - 0 (Transcription Factors) RN - 0 (Antigens, Neoplasm) RN - 0 (PRAME protein, human) SB - IM MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Reverse Transcription MH - *Melanoma/diagnosis/genetics/metabolism MH - *Skin Neoplasms/diagnosis/genetics/pathology MH - *Nevus, Pigmented/diagnosis/genetics/pathology MH - *Nevus MH - *Melanosis/diagnosis/genetics MH - Polymerase Chain Reaction MH - Transcription Factors/genetics MH - Antigens, Neoplasm/genetics/analysis MH - Melanoma, Cutaneous Malignant OTO - NOTNLM OT - Conjunctival melanocytic intraepithelial lesion OT - Conjunctival melanoma OT - Conjunctival nevi OT - Fluorescence in situ hybridization OT - PRAME OT - Reverse transcription quantitative PCR EDAT- 2023/02/23 06:00 MHDA- 2023/04/03 06:41 CRDT- 2023/02/22 09:04 PHST- 2022/12/15 00:00 [received] PHST- 2023/01/28 00:00 [revised] PHST- 2023/02/04 00:00 [accepted] PHST- 2023/04/03 06:41 [medline] PHST- 2023/02/23 06:00 [pubmed] PHST- 2023/02/22 09:04 [entrez] AID - S0046-8177(23)00030-8 [pii] AID - 10.1016/j.humpath.2023.02.002 [doi] PST - ppublish SO - Hum Pathol. 2023 Apr;134:1-18. doi: 10.1016/j.humpath.2023.02.002. Epub 2023 Feb 16.