ArticlePloS one2012
A seven-marker signature and clinical outcome in malignant melanoma: a large-scale tissue-microarray study with two independent patient cohorts.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
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Who cites it
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.Annals of oncology : official journal of the European Society for Medical Oncology · 2025Guideline
- Construction and analysis of multiparameter prognostic models for melanoma outcome.Methods in molecular biology (Clifton, N.J.) · 2014Pooled it
- Tumor-associated B-cells induce tumor heterogeneity and therapy resistance.Nature communications · 2017Trial
- Exploring uncertainties in melanoma management: a Spanish multidisciplinary Delphi consensus.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- [Biomarkers in adjuvant and neoadjuvant treatment of melanoma].Dermatologie (Heidelberg, Germany) · 2025Review
- Prognostic Biomarkers in Evolving Melanoma Immunotherapy.American journal of clinical dermatology · 2025Review
- B cells enhance IL-1 beta driven invasiveness in triple negative breast cancer.Scientific reports · 2025Article
- B cells enhance IL-1 beta driven invasiveness in triple-negative breast cancer.Research square · 2024Article
- Immune Checkpoints and Cellular Landscape of the Tumor Microenvironment in Non-Melanoma Skin Cancer (NMSC).Cells · 2024Review
- Novel Prognostic Markers for Skin Cutaneous Melanoma.Clinical, cosmetic and investigational dermatology · 2024Article
- The role of tissue-resident memory T cells as mediators for response and toxicity in immunotherapy-treated melanoma-two sides of the same coin?Frontiers in immunology · 2024Review
- Analytical Validation of an Immunohistochemical 7-Biomarker Prognostic Assay (immunoprintDiagnostics (Basel, Switzerland) · 2023Article
- Tumor-associated immune cell infiltrate density in penile squamous cell carcinomas.Virchows Archiv : an international journal of pathology · 2022Article
- A B-cell or a key player? The different roles of B-cells and antibodies in melanoma.Pigment cell & melanoma research · 2022Review
- Risk Stratification and Clinical Characteristics of Patients with Late Recurrence of Melanoma (>10 Years).Journal of clinical medicine · 2022Article
- Immune Landscape and an RBM38-Associated Immune Prognostic Model with Laboratory Verification in Malignant Melanoma.Cancers · 2022Article
- Tumor-B-cell interactions promote isotype switching to an immunosuppressive IgG4 antibody response through upregulation of IL-10 in triple negative breast cancers.Journal of translational medicine · 2022Article
- Associations of immune cell homing gene signatures and infiltrates of lymphocyte subsets in human melanomas: discordance with CD163Journal of translational medicine · 2021Article
- Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma.Cancer cell international · 2021Article
- Distinct Molecular Mechanisms of Altered HLA Class II Expression in Malignant Melanoma.Cancers · 2021Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrent staging methods such as tumor thickness, ulceration and invasion of the sentinel node are known to be prognostic parameters in patients with malignant melanoma (MM). However, predictive molecular marker profiles for risk stratification and therapy optimization are not yet available for routine clinical assessment. METHODS AND
findingsUsing tissue microarrays, we retrospectively analyzed samples from 364 patients with primary MM. We investigated a panel of 70 immunohistochemical (IHC) antibodies for cell cycle, apoptosis, DNA mismatch repair, differentiation, proliferation, cell adhesion, signaling and metabolism. A marker selection procedure based on univariate Cox regression and multiple testing correction was employed to correlate the IHC expression data with the clinical follow-up (overall and recurrence-free survival). The model was thoroughly evaluated with two different cross validation experiments, a permutation test and a multivariate Cox regression analysis. In addition, the predictive power of the identified marker signature was validated on a second independent external test cohort (n=225). A signature of seven biomarkers (Bax, Bcl-X, PTEN, COX-2, loss of β-Catenin, loss of MTAP, and presence of CD20 positive B-lymphocytes) was found to be an independent negative predictor for overall and recurrence-free survival in patients with MM. The seven-marker signature could also predict a high risk of disease recurrence in patients with localized primary MM stage pT1-2 (tumor thickness ≤2.00 mm). In particular, three of these markers (MTAP, COX-2, Bcl-X) were shown to offer direct therapeutic implications.
conclusionsThe seven-marker signature might serve as a prognostic tool enabling physicians to selectively triage, at the time of diagnosis, the subset of high recurrence risk stage I-II patients for adjuvant therapy. Selective treatment of those patients that are more likely to develop distant metastatic disease could potentially lower the burden of untreatable metastatic melanoma and revolutionize the therapeutic management of MM.
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