A Prognostic Gene Signature Expressed in Primary Cutaneous Melanoma: Synergism With Conventional Staging

Area of Science:

• Oncology
• Molecular Biology
• Biomarker Discovery

Background:

• Current American Joint Committee on Cancer (AJCC) staging for cutaneous melanoma has limitations in predicting clinical outcomes.
• Complementary biomarkers for routine prognostic assessment are lacking.
• Gene signatures identified in fresh-frozen (FF) melanomas were adapted for formalin-fixed paraffin-embedded (FFPE) samples.

Purpose of the Study:

• To develop a gene expression profiling (GEP) score for prognostic assessment of primary cutaneous melanoma.
• To adapt a previously identified gene signature for use with FFPE melanoma tissues.
• To define patient survival probability at the time of initial diagnosis.

Main Methods:

• Expression of 11 FF melanoma signature genes was quantified using reverse transcription polymerase chain reaction in an FFPE training cohort (n=125).
• A prognostic eight-gene signature was identified in tumor and adjacent tissues of AJCC stage I-III melanomas.
• The GEP score was technically and clinically validated in an independent FFPE melanoma cohort (n=211).

Main Results:

• The GEP score correlated significantly with melanoma-specific survival (MSS) (P < .0001).
• The score was independent of tumor stage and stroma content, and complemented AJCC staging (AUC = 0.91).
• In validation, the GEP score remained significant (P = .0131) and demonstrated high reproducibility (93%).

Conclusions:

• The GEP score serves as a clinically significant prognostic tool for melanoma.
• It provides additional prognostic information beyond conventional staging.
• The GEP score enhances the prediction of melanoma-specific survival.