Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Clin Oncol. 2009 Dec 1;27(34):5772-80. doi: 10.1200/JCO.2009.22.8239. Epub 2009 Nov 2.

Melanoma prognostic model using tissue microarrays and genetic algorithms.

Author information

  • 1Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023, USA.

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.

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.

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.

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.

PMID:
19884546
[PubMed - indexed for MEDLINE]
PMCID:
PMC2792999
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk