Multiple predictive biomarker testing in melanoma: Another challenge in identifying the optimal approach on cytological samples

Cytopathology. 2023 May;34(3):198-203. doi: 10.1111/cyt.13211. Epub 2023 Feb 8.

Abstract

Background: The management of cutaneous melanoma has changed dramatically in recent years thanks to the development of tyrosine kinase and immune-checkpoint inhibitors (ICIs). Thus, multiple biomarker testing is becoming ever more important for the identification of patients who are potentially eligible for these treatments. One reliable approach to the molecular evaluation of metastatic melanoma is fine needle cytology (FNC). To examine the utility of this approach for assessing PD-L1 expression levels, we evaluated the cellular adequacy of residual cell block (CB) material from metastatic melanomas that were previously tested for BRAF and NRAS mutations.

Methods: We retrieved from our internal archives a series of FNC samples of metastatic melanoma that had been subjected to molecular testing on residual CB material or a dedicated needle rinse between January 2016 and July 2022. Real-time polymerase chain reaction was used to assess BRAF and NRAS status, and an SP263 assay was employed to ascertain PD-L1 expression levels.

Results: Overall, n = 19 cases were selected. Of these, 11 (57.9%) cases revealed a BRAF exon 15 p.V600E mutation, one case (5.3%) revealed NRAS mutation, and seven cases (36.8%) showed no mutations. Regarding PD-L1 assessment, 16/19 (84.2%) cases were deemed adequate, meaning they contained at least 100 viable cells.

Conclusions: We highlighted the feasibility of assessing PD-L1 expression levels in residual CB material from metastatic melanomas previously tested for BRAF and NRAS mutations. Moreover, we pointed out that FNC needle rinses may be an alternative source of nucleic acids for molecular testing, preserving CB material for immunocytochemistry evaluation.

Keywords: PD-L1; fine needle cytology; immunotherapy; melanoma; molecular biology.

MeSH terms

  • B7-H1 Antigen
  • Biomarkers
  • GTP Phosphohydrolases / genetics
  • Humans
  • Melanoma* / diagnosis
  • Melanoma* / genetics
  • Melanoma, Cutaneous Malignant
  • Proto-Oncogene Proteins B-raf / genetics
  • Skin Neoplasms* / diagnosis
  • Skin Neoplasms* / genetics

Substances

  • B7-H1 Antigen
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • Biomarkers