Preferentially Expressed Antigen in Melanoma (PRAME) Expression in Malignant, but Not Benign, Peripheral Nerve Sheath Tumors

Cadwell, Cathryn R.; Yuksek, Gul Emek; Hirbe, Angela C.; Srihari, Divya; LeBoit, P. E.; Dahiya, Sonika; Pekmezci, Melike

doi:10.1093/jnen/nlaa125

Cited by 8 publications

(16 citation statements)

References 8 publications

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“…The first data are in line with those found by previous studies and suggest to evaluate PRAME comparing multiple lesions of the same patients (M, NN, MM) in association with histology and additional S (HMB45, Ki-67, p16; patient #15). The second point shows as, although a diffuse positivity for PRAME (4+) could reasonably favor a diagnosis of M in the appropriate clinical set, rare cases of M and MM could be negative for PRAME (patient #15), as well as other tumors (sarcomas, carcinomas of the female genital tracts, leukemias and germ cell tumors) could be positive for PRAME 12–20. In this context, DS showing positivity for both PRAME and melanocytic markers (Melan A and HMB45) strongly encourages a diagnosis of M, especially on small/incisional biopsies with the risk that material could be consumed on serial sections.…”

Section: Resultsmentioning

confidence: 97%

“…The second point shows as, although a diffuse positivity for PRAME (4+) could reasonably favor a diagnosis of M in the appropriate clinical set, rare cases of M and MM could be negative for PRAME (patient #15), as well as other tumors (sarcomas, carcinomas of the female genital tracts, leukemias and germ cell tumors) could be positive for PRAME. [12][13][14][15][16][17][18][19][20] In this context, DS showing positivity for both PRAME and melanocytic markers (Melan A and HMB45) strongly encourages a diagnosis of M, especially on small/incisional biopsies with the risk that material could be consumed on serial sections. Last, DS showed more intense staining for HMB45 rather than Melan A, with Melan A being more intense in SS rather than in DS (Table 2, Fig.…”

Section: Resultsmentioning

confidence: 99%

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HMB45/PRAME, a Novel Double Staining for the Diagnosis of Melanocytic Neoplasms: Technical Aspects, Results, and Comparison With Other Commercially Available Staining (PRAME and Melan A/PRAME)

Grillini

Ricci

Pino

et al. 2021

Applied Immunohistochemistry &Amp; Molecular Morphology

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PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen that was recently found to be expressed by malignant melanocytic lesions but not by benign ones, thus resulting useful in this diagnostic field. PRAME could also be expressed by some normal tissues and nonmelanocytic tumors, suggesting as caution should be adopted to use PRAME as a "pan-melanoma" marker for the differential diagnosis with other malignant tumors. Until now, PRAME expression was exclusively investigated through single staining with a monoclonal antibody targeting PRAME and with double staining for Melan A/PRAME found to be useful in specific diagnostic sets. Herein, we studied the expression of PRAME in 40 melanocytic lesions and 23 nonmelanocytic ones using PRAME, Melan A/ PRAME, and novel double staining for HMB45/PRAME. Although our results need to be validated, they support the adoption of HMB45/PRAME, alone or in combination with PRAME and Melan A/PRAME, as a helpful marker in the diagnosis of melanocytic neoplasms with a high concordance rate between primary melanoma and corresponding metastases.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

HMB45/PRAME, a Novel Double Staining for the Diagnosis of Melanocytic Neoplasms: Technical Aspects, Results, and Comparison With Other Commercially Available Staining (PRAME and Melan A/PRAME)

Grillini

Ricci

Pino

et al. 2021

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…This study also noted perivascular accentuation of staining within tumor cells with a similar conclusion that these ndings are likely secondary to the rapid growth and tissue ischemia. 13 While this pattern was not seen in the melanomas, all melanomas tested were smaller cutaneous lesions that were unlikely to demonstrate the same degree of ischemia; it is unknown if this pattern could be seen in larger metastatic melanomas exhibiting rapid growth.…”

Section: Discussionmentioning

confidence: 93%

“…12 To our knowledge, Caldwell et al have the only published study evaluating the diagnostic utility of PRAME immunohistochemistry (IHC) in MPNSTs compared to benign peripheral nerve sheath tumors with up to 65% of MPNSTs demonstrating PRAME labeling. 13 Due to the rarity of MPNSTs and DMs, the evaluation of large cohorts is problematic, and further investigation is warranted to characterize PRAME IHC labeling patterns fully. Our goal is to assess the diagnostic utility in the PRAME IHC marker in the context of distinguishing MPNSTs from histomorphologically similar melanomas, speci cally spindle cell melanomas.…”

Section: Desmoplastic Melanomasmentioning

confidence: 99%

Preferentially Expressed Antigen in Melanoma (PRAME) Expression Utility in Distinguishing Desmoplastic and Spindle Cell Melanomas from Malignant Peripheral Nerve Sheath Tumors

Hall

Torrko

Santiago

et al. 2022

Preprint

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Spindle cell and desmoplastic melanoma (DM) are uncommon melanoma subtypes; both are composed of elongated “spindled cells” but differ from one another based on the extent of desmoplastic stroma separating individual tumor cells. These can be challenging lesions that often have absent or decreased staining for melanocyte specific markers and may resemble other tumors with spindle cell morphology and a similar immunohistochemical (IHC) staining profile, in particular malignant peripheral nerve sheath tumors (MPNSTs). We evaluated IHC expression of PRAME (Preferentially Expressed Antigen in Melanoma) in 41 DMs, 14 spindle cell melanomas, and 26 MPNSTs. PRAME expression was found in 68% of DM, 71% of spindle cell melanomas, and 84% of MPNSTs. However, when extent and intensity of expression are considered, significant differences emerge. The median H-score for all melanomas was 167.5 (range, 20 to 270) and 80 (range, 20 to 275) for all MPNSTs. Spindle cell melanoma, which often has the closest histologic appearance to MPNST, demonstrated the highest median H-score of 215 (range, 55 to 270). Furthermore, a strong and diffuse staining pattern was identified in 53% of all melanomas and 80% of spindle cell melanomas compared to strong, diffuse staining found in 29% of all MPNSTs and only 17% of MPNSTs with intact H3K27me3 expression.

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“…PRAME (PReferentially expressed Antigen in MElanoma) is a tumour‐associated antigen in the family of cancer testis antigens. Its expression is minimal in normal adult human tissues and is largely limited to the gonads 1,2 . PRAME expression has been reported in various neoplasms including melanoma, breast carcinoma, renal cell carcinoma, non‐small cell lung carcinoma, neuroblastoma, acute leukaemia, and several types of sarcomas 2–10 .…”

Section: Introductionmentioning

confidence: 99%

PRAME expression in spindle cell melanoma, malignant peripheral nerve sheath tumour, and other cutaneous sarcomatoid neoplasms: a comparative analysis

et al. 2022

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PRAME expression in spindle cell melanoma, malignant peripheral nerve sheath tumour, and other cutaneous sarcomatoid neoplasms: a comparative analysis Diagnosis of spindle cell/sarcomatoid melanoma may be challenging due to frequent loss of expression of melanocytic marker(s) and histomorphologic resemblance to various mesenchymal tumours, particularly malignant peripheral nerve sheath tumour (MPNST). Overexpression of PReferentially expressed Antigen in MElanoma (PRAME) supports a diagnosis of melanoma when evaluating challenging melanocytic tumours. PRAME expression in MPNST and other cutaneous sarcomatoid neoplasms, however, has not been well characterised. We aimed to determine the utility of PRAME immunostain in distinguishing spindle cell melanoma from MPNST and other sarcomatoid mimics. PRAME expression was scored by extent (0 to 4+) and intensity (0 to 3) of staining. A strong positive correlation was observed between the extent and intensity scores (r = 0.84). An extent score of 4+, defined by staining in 76-100% of tumour cells, was seen in 56% (23/41) of spindle cell melanomas, 18% (7/38) of MPNSTs, 15% (4/27) of cutaneous sarcomatoid squamous cell carcinomas (SCCs), 33% (5/15) of poorly differentiated cutaneous angiosarcomas, 12% (4/33) of atypical fibroxanthomas (AFXs), 4% (1/25) of pleomorphic dermal sarcomas (PDSs), and none (0/16) of the highgrade cutaneous leiomyosarcomas. A significant difference was found between spindle cell melanoma and all other examined sarcomatoid neoplasms except angiosarcoma. While diffuse (and often strong) PRAME expression is more frequently observed in spindle cell melanoma than MPNST, sarcomatoid SCC, AFX, PDS, and high-grade leiomyosarcoma, its limited sensitivity and specificity caution against its use as a standalone diagnostic marker. PRAME may complement other epigenetic or lineage-specific markers and should only be used as part of an immunohistochemical panel when evaluating these sarcomatoid neoplasms.

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Preferentially Expressed Antigen in Melanoma (PRAME) Expression in Malignant, but Not Benign, Peripheral Nerve Sheath Tumors

Cited by 8 publications

References 8 publications

HMB45/PRAME, a Novel Double Staining for the Diagnosis of Melanocytic Neoplasms: Technical Aspects, Results, and Comparison With Other Commercially Available Staining (PRAME and Melan A/PRAME)

HMB45/PRAME, a Novel Double Staining for the Diagnosis of Melanocytic Neoplasms: Technical Aspects, Results, and Comparison With Other Commercially Available Staining (PRAME and Melan A/PRAME)

Preferentially Expressed Antigen in Melanoma (PRAME) Expression Utility in Distinguishing Desmoplastic and Spindle Cell Melanomas from Malignant Peripheral Nerve Sheath Tumors

PRAME expression in spindle cell melanoma, malignant peripheral nerve sheath tumour, and other cutaneous sarcomatoid neoplasms: a comparative analysis

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