Identification of high-risk patients with a seven-biomarker prognostic signature for adjuvant treatment trial recruitment in American Joint Committee on Cancer v8 stage I-IIA cutaneous melanoma

Eur J Cancer. 2023 Mar:182:77-86. doi: 10.1016/j.ejca.2023.01.002. Epub 2023 Jan 7.


Purpose: Many patients with resected American Joint Committee on Cancer (AJCC) early-stage cutaneous melanoma nonetheless die of melanoma; additional risk stratification approaches are needed.

Patients and methods: Using prospectively-collected whole-tissue sections, we assessed in consecutive stage I-IIA patients (N = 439), a previously-validated, immunohistochemistry-based, 7-biomarker signature to prognosticate disease-free survival (DFS), melanoma-specific survival (MSS; primary end-point) and overall survival (OS), independent of AJCC classification.

Results: Seven-marker signature testing designated 25.1% of patients (110/439) as high-risk (stage IA, 13.3% [43/323], IB, 53.2% [42/79], and IIA, 67.6% [25/37]). A Kaplan-Meier analysis demonstrated high-risk patients to have significantly worse DFS, MSS and OS versus low-risk counterparts (P < 0.001). In multivariable Cox regression modelling also including key clinicopathological/demographic factors, 7-marker signature data independently prognosticated the studied end-points. Models with the 7-marker signature risk category plus clinicopathological/demographic covariates substantially outperformed models with clinicopathological/demographic variables alone in predicting all studied outcomes (areas under the receiver operator characteristic curve 74.1% versus 68.4% for DFS, 81.5% versus 71.2% for MSS, 80.9% versus 73.0% for OS; absolute differences 5.7%, 10.3% and 7.9%, respectively, favouring 7-marker signature risk category-containing models).

Conclusion: In patients with AJCC early-stage disease, the 7-marker signature reliably prognosticates melanoma-related outcomes, independent of AJCC classification, and provides a valuable complement to clinicopathological/demographic factors.

Keywords: Data collection; Disease-free survival (DFS); Malignant melanoma; Prognostic factor; Prospective studies; Risk assessment; Survival; Tumour staging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Humans
  • Melanoma* / pathology
  • Melanoma, Cutaneous Malignant
  • Neoplasm Staging
  • Prognosis
  • Skin Neoplasms* / pathology
  • United States


  • Biomarkers