<scp>PRAME</scp> immunohistochemistry is useful in differentiating oral melanomas from nevi and melanotic macules

Schmitt, Toby A; Lee, Jonathan Cassolato; Martinka, Magdalena; Ko, Kevin Yen Chen

doi:10.1111/cup.14361

Cited by 4 publications

(4 citation statements)

References 17 publications

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“…A single case of PAM without atypia was reported to show 4+ PRAME immunoreactivity. [94][95][96] Most (83.7%-100%) mucosal melanomas of sinonasal, gastrointestinal, genitourinary, oral cavity, and oropharyngeal origin have consistently been reported to show diffuse immunoreactivity for PRAME, 33,78,[97][98][99] and in one study a trend toward higher PRAME expression in mucosal melanomas with epithelioid versus spindle cell morphology was noted, 100 similar to findings in cutaneous melanomas. Oral nevi and melanotic macules evaluated in one study were completely negative for PRAME.…”

Section: Prame Ihc In Mucosal Melanocytic Lesions and Uveal Melanomasmentioning

confidence: 64%

“…Oral nevi and melanotic macules evaluated in one study were completely negative for PRAME. 99 In uveal melanomas, PRAME mRNA expression is used as a biomarker for higher risk of metastasis and aggressive tumor behavior. 24,25 immunoreactivity and overall good concordance with PRAME mRNA detection by RT-PCR.…”

Section: Prame Ihc In Mucosal Melanocytic Lesions and Uveal Melanomasmentioning

confidence: 99%

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Immunohistochemistry for PRAME in Dermatopathology

Lezcano,

Jungbluth,

Busam

2023

The American Journal of Dermatopathology

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Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen first identified in a melanoma patient and found to be expressed in most melanomas as well as in variable levels in other malignant neoplasms of epithelial, mesenchymal, or hematolymphoid lineage. Detection of PRAME expression in formalin-fixed paraffin-embedded tissue is possible by immunohistochemistry (IHC) with commercially available monoclonal antibodies. In situ and invasive melanoma frequently show a diffuse pattern of nuclear PRAME immunoreactivity which contrasts with the infrequent and typically nondiffuse staining seen in nevi. In many challenging melanocytic tumors, results of PRAME IHC and other ancillary tests correlate well, but not always: The tests are not interchangeable. Most metastatic melanomas are positive for PRAME, whereas nodal nevi are not. Numerous studies on PRAME IHC have become available in the past few years with results supporting the value of PRAME IHC as an ancillary tool in the evaluation of melanocytic lesions and providing insights into limitations in sensitivity and specificity as well as possible pitfalls that need to be kept in mind by practicing pathologists.

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Section: Prame Ihc In Mucosal Melanocytic Lesions and Uveal Melanomasmentioning

confidence: 64%

Section: Prame Ihc In Mucosal Melanocytic Lesions and Uveal Melanomasmentioning

confidence: 99%

Immunohistochemistry for PRAME in Dermatopathology

Lezcano,

Jungbluth,

Busam

2023

The American Journal of Dermatopathology

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“…Preferentially Expressed Antigen in Melanoma (PRAME) has recently emerged as a candidate diagnostic biomarker that can be detected using standard immunohistochemistry (1)(2)(3)(4). Studies have shown immunostains for PRAME to represent a means of ancillary histopathology testing with high sensitivity and specificity for melanoma diagnosis, including ambiguous melanocytic neoplasms (1,5,6) and rare subtypes of melanoma (7)(8)(9)(10). This specificity arises because PRAME, a membrane-bound antigen, is not typically expressed in normal cells except for the testis (11,12).…”

Section: Introductionmentioning

confidence: 99%

PRAME expression in melanoma is negatively regulated by TET2-mediated DNA hydroxymethylation

Fang,

Vallius,

Zhang

et al. 2024

Preprint

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Preferentially Expressed Antigen in Melanoma (PRAME) and Ten-Eleven Translocation (TET) dioxygenase-mediated 5-hydroxymethylcytosine (5hmC) are emerging melanoma biomarkers. We observed an inverse correlation between PRAME expression and 5hmC levels in benign nevi, melanoma in situ, primary invasive melanoma, and metastatic melanomas via immunohistochemistry and multiplex immunofluorescence: nevi exhibited high 5hmC and low PRAME, whereas melanomas showed the opposite pattern. Single-cell multiplex imaging of melanoma precursors revealed that diminished 5hmC coincides with PRAME upregulation in premalignant cells. Analysis of TCGA and GTEx databases confirmed a negative relationship between TET2 and PRAME mRNA expression in melanoma. Additionally, 5hmC levels were reduced at the PRAME 5′ promoter in melanoma compared to nevi, suggesting a role for 5hmC in PRAME transcription. Restoring 5hmC levels via TET2 overexpression notably reduced PRAME expression in melanoma cell lines. These findings establish a function of TET2-mediated DNA hydroxymethylation in regulating PRAME expression and demonstrate epigenetic reprogramming as pivotal in melanoma tumorigenesis.

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“…PRAME expression by immunohistochemistry (IHC) effectively discriminates cutaneous 5,12 , oral mucosal 13 , and uveal 14 melanomas from atypical nevi. Only nuclear staining of PRAME is considered positive, and expression in >75% of malignant cells is observed in 83% of primary cutaneous melanomas, thereby constituting a malignant PRAME expression pattern.…”

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confidence: 99%

PRAME Immunohistochemistry for Distinguishing Vulvar and Vaginal Melanoma From Benign Melanocytic Nevi

Martin,

Gilks

et al. 2023

International Journal of Gynecological Pathology

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Vulvovaginal melanoma (VVM) is a rare but deadly disease, accounting for 5% of all vulvar malignancies, with a 5-yr survival rate of only 47% for all stages of the disease. VVM is a distinct subset of melanoma, with a unique genomic profile and underlying pathogenesis unassociated with sun exposure. Distinguishing these rare malignancies from very common pigmented lesions of the vulva and vagina is challenging as histologic features often overlap between entities. PReferentially expressed Antigen in MElanoma (PRAME) is a melanoma-associated protein, and immunohistochemistry (IHC) for PRAME distinguishes cutaneous, oral mucosal, and retinal melanoma from atypical nevi. Given the biological differences between VVM and cutaneous melanoma, the utility of PRAME IHC for the diagnosis of VVM is unknown. We accrued a cohort of 20 VVM and 21 benign vulvar melanocytic nevi. We found that nuclear PRAME IHC staining with 4+ intensity was present in 85% of the VVM and 0% of the nevi. With the assistance of PRAME IHC, we found evidence of close or positive margin involvement in 3 of 10 cases where margins were originally diagnosed as negative for melanoma in situ. Our study is the first to assess PRAME IHC in a cohort of VVM cases and provides confidence for using PRAME IHC to assist with diagnosis and margin assessment in this rare disease.

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PRAME immunohistochemistry is useful in differentiating oral melanomas from nevi and melanotic macules

Cited by 4 publications

References 17 publications

Immunohistochemistry for PRAME in Dermatopathology

Immunohistochemistry for PRAME in Dermatopathology

PRAME expression in melanoma is negatively regulated by TET2-mediated DNA hydroxymethylation

PRAME Immunohistochemistry for Distinguishing Vulvar and Vaginal Melanoma From Benign Melanocytic Nevi

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