Diagnostic test accuracy meta‐analysis of PRAME in distinguishing primary cutaneous melanomas from benign melanocytic lesions

Abstract

Diagnostic test accuracy meta-analysis of PRAME in distinguishing primary cutaneous melanomas from benign melanocytic lesions PRAME is a novel immunohistochemical marker that aids the diagnosis of melanocytic lesions. Diffuse PRAME positivity suggests melanoma, whereas benign naevi are negative or only weakly positive. However, the factual diagnostic accuracy of PRAME is not well established. Moreover, some studies have suggested that the threshold of 3+/50% positive cells may be more useful in practice than the most widely used cut-off (4+/75% of positive cells). Hence, we performed a systematic review and diagnostic accuracy meta-analysis to evaluate sensitivity, specificity, likelihood ratios and optimal threshold for PRAME in distinguishing benign melanocytic proliferations from melanomas. Twenty-six studies were enrolled into the meta-analysis. A total of 2915 melanocytic lesions were analysed. The optimal threshold for PRAME positivity was estimated at 3.11, which translates into 3+ in practice. Sensitivity and specificity calculated from SROC at the 3+ threshold were 0.735 (0.631-0.818) and 0.915 (0.834-0.958), respectively, compared to 0.679 (0.559-0.957) and 0.957 (0.908-0.981) at the 4+ cut-off. In subgroup analysis, the spitzoid subgroup was characterised by the lowest sensitivity and diagnostic odds ratio of PRAME. Our findings indicate that PRAME immunohistochemistry may serve as an ancillary marker to support the diagnosis of melanoma. Nevertheless, the accuracy of PRAME may be lower in spitzoid neoplasms. Our meta-analysis suggests that the 3+/50% threshold might be more useful in practice than the 4+/75% cut-off, as it shows higher sensitivity with retained satisfactory specificity.

Restrospective reappraisal of the prognostic classification of spitzoid melanocytic neoplasms after BRAF and NRAS mutation characterisation: a single institution experience

“…Recently, preferentially expressed antigen in melanoma (PRAME) expression has been reported to be a useful adjunctive marker to diagnose melanocytic proliferations. 11,12 However, in ambiguous spitzoid neoplasms, the low sensitivity of PRAME expression when compared to cytogenetic techniques used in establishing the risk of progression of the tumours has been reported previously. 12,23,24 In our study, 36% of SM and 50% of MSF tested negative (Table 4), but no intermediate-grade cases showed PRAME expression of more than 50% of positive The strength of our study relies upon the presentation of a large series of spitzoid neoplasms with atypical features in which the risk of progression has been **p16 significant loss was considered when completely negative groups of tumour cells in dermis were observed.…”

“…11,12 However, in ambiguous spitzoid neoplasms, the low sensitivity of PRAME expression when compared to cytogenetic techniques used in establishing the risk of progression of the tumours has been reported previously. 12,23,24 In our study, 36% of SM and 50% of MSF tested negative (Table 4), but no intermediate-grade cases showed PRAME expression of more than 50% of positive The strength of our study relies upon the presentation of a large series of spitzoid neoplasms with atypical features in which the risk of progression has been **p16 significant loss was considered when completely negative groups of tumour cells in dermis were observed. ***The immunohistochemical results of these markers (Ki67, HMB45, p16 and PRAME) had been taken into account when classifying the tumours, and the differences between groups cannot be considered independent results.…”

“…Recently, preferentially expressed antigen in melanoma (PRAME) expression has been reported to be a useful adjunctive marker to diagnose melanocytic proliferations 11,12 . However, in ambiguous spitzoid neoplasms, the low sensitivity of PRAME expression when compared to cytogenetic techniques used in establishing the risk of progression of the tumours has been reported previously 12,23,24 .…”

“…PRAME was assessed in five grades; 11 0, negative stain, 1+, positivity in 1–25% of cells; 2+, positivity in 26–50% of cells; 3+, positivity in 51–75%; and 4+: positivity in 76% or more of cells. For analytical purposes, cases 3+ and 4+ were considered positive 12 …”

“…For analytical purposes, cases 3+ and 4+ were considered positive. 12 ALK and NTRK cytoplasmic expression of any intensity and BAP-1 nuclear expression were assessed in all cases.…”