The diagnostic utility of PRAME and p16 in distinguishing nodal nevi from nodal metastatic melanoma

Pathol Res Pract. 2020 Sep;216(9):153105. doi: 10.1016/j.prp.2020.153105. Epub 2020 Jul 11.

Abstract

The status of the sentinel lymph node is the strongest predictor of recurrence in patients with malignant melanoma, making accurate distinction between nodal metastases and nodal nevi of paramount importance. We explored the utility of p16 and PRAME in differentiating nodal nevi from metastatic melanoma by immunohistochemistry. We searched our institutional database for cases of nodal nevi and nodal metastatic melanoma. p16 and PRAME expression were assessed with immunolabeling quantified by extent of nuclear positivity (0-25 %, >25 %-50 %, >50 %-75 % and >75 %). Sensitivities and specificities were calculated, and discrimination assessed using the area under the receiver operating characteristic curve (AUC). Forty-nine cases out of 51 nevi and 56/56 melanoma cases had lesional tissue present for p16, while 44/51 nevi and 54/56 melanoma cases had lesional tissue present for PRAME. 43 nodal nevi (88 %) had >50 % nuclear staining for p16, while none had >50 % staining for PRAME. More than half (55 %) of melanoma cases had complete loss of nuclear staining for p16, while majority (94 %) had >50 % nuclear staining for PRAME. Using a cut-off value of 50 %, higher PRAME expression had a sensitivity and specificity of 94 % and 100 %, respectively, while lower p16 expression had a sensitivity and specificity of 66 % and 88 %, respectively, for detecting metastatic melanoma. PRAME showed significantly better discrimination (AUC = 0.97, 95 % CI 0.94-1.00) than p16 (AUC = 0.77, 95 % CI 0.68-0.86) for differentiating nodal nevi from nodal melanoma (P < 0.001). Our findings suggest that PRAME is more accurate than p16 in discriminating between the two entities, with excellent sensitivity and specificity.

Keywords: Lymph node; Melanoma; Nevus/nevi; PRAME; p16.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / analysis
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Diagnosis, Differential
  • Female
  • Humans
  • Lymphatic Metastasis / pathology
  • Male
  • Melanoma / diagnosis
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Melanoma, Cutaneous Malignant
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasms, Second Primary / diagnosis
  • Neoplasms, Second Primary / pathology
  • Nevus, Pigmented / diagnosis
  • Nevus, Pigmented / pathology*
  • Sentinel Lymph Node Biopsy / methods
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • PRAME protein, human