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Melanoma prognostic model using tissue microarrays and genetic algorithms.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2009 Dec 01; Vol. 27 (34), pp. 5772-80. Date of Electronic Publication: 2009 Nov 02. - Publication Year :
- 2009
-
Abstract
- Purpose: As a result of the questionable risk-to-benefit ratio of adjuvant therapies, stage II melanoma is currently managed by observation because available clinicopathologic parameters cannot identify the 20% to 60% of such patients likely to develop metastatic disease. Here, we propose a multimarker molecular prognostic assay that can help triage patients at increased risk of recurrence.<br />Methods: Protein expression for 38 candidates relevant to melanoma oncogenesis was evaluated using the automated quantitative analysis (AQUA) method for immunofluorescence-based immunohistochemistry in formalin-fixed, paraffin-embedded specimens from a cohort of 192 primary melanomas collected during 1959 to 1994. The prognostic assay was built using a genetic algorithm and validated on an independent cohort of 246 serial primary melanomas collected from 1997 to 2004.<br />Results: Multiple iterations of the genetic algorithm yielded a consistent five-marker solution. A favorable prognosis was predicted by ATF2 ln(non-nuclear/nuclear AQUA score ratio) of more than -0.052, p21(WAF1) nuclear compartment AQUA score of more than 12.98, p16(INK4A) ln(non-nuclear/nuclear AQUA score ratio) of < or = -0.083, beta-catenin total AQUA score of more than 38.68, and fibronectin total AQUA score of < or = 57.93. Primary tumors that met at least four of these five conditions were considered a low-risk group, and those that met three or fewer conditions formed a high-risk group (log-rank P < .0001). Multivariable proportional hazards analysis adjusting for clinicopathologic parameters shows that the high-risk group has significantly reduced survival on both the discovery (hazard ratio = 2.84; 95% CI, 1.46 to 5.49; P = .002) and validation (hazard ratio = 2.72; 95% CI, 1.12 to 6.58; P = .027) cohorts.<br />Conclusion: This multimarker prognostic assay, an independent determinant of melanoma survival, might be beneficial in improving the selection of stage II patients for adjuvant therapy.
- Subjects :
- Activating Transcription Factor 2 analysis
Algorithms
Cyclin-Dependent Kinase Inhibitor p16 analysis
Cyclin-Dependent Kinase Inhibitor p21 analysis
Disease-Free Survival
Female
Humans
Male
Melanoma mortality
Melanoma secondary
Middle Aged
Prognosis
Skin Neoplasms mortality
Skin Neoplasms pathology
Survival Rate
beta Catenin analysis
Biomarkers, Tumor analysis
Melanoma chemistry
Protein Array Analysis
Skin Neoplasms chemistry
Tissue Array Analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 27
- Issue :
- 34
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 19884546
- Full Text :
- https://doi.org/10.1200/JCO.2009.22.8239