A multimarker prognostic assay for primary cutaneous melanoma.
OBJECTIVE
To determine the prognostic significance of a multimarker assay incorporating expression levels of three molecular markers in primary cutaneous melanoma.


METHODS
We assessed expression levels of NCOA3, SPP1, and RGS1 using immunohistochemical analysis in a tissue microarray cohort of 395 patients. For each marker, we identified optimal cut-points for expression intensity to predict disease-specific survival (DSS) and, as a secondary endpoint, sentinel lymph node (SLN) status. The cumulative overexpression of all three markers was embodied in a multimarker index, and its prognostic effect on DSS and SLN status was assessed using Cox regression, Kaplan-Meier analysis, and logistic regression. The prognostic effect of this multimarker assay on DSS was assessed in an independent cohort of 141 patients, in which marker expression levels were scored using immunohistochemical analysis of stained tissue sections.


RESULTS
Increasing multimarker index scores were significantly predictive of reduced DSS and increased SLN metastasis in the 395-patient cohort. Multivariate logistic regression analysis revealed multimarker expression scores as an independent predictor of SLN status (P = 0.001). Multivariate Cox regression analysis showed the independent effect of the multimarker index on DSS (P < 0.001). The multimarker index was the most significant factor predicting DSS when compared with other clinical and histologic factors, including SLN status (P = 0.002). Multimarker expression scores were also the most significantly predictive of DSS in the independent cohort (P = 0.01).


CONCLUSIONS
These results describe a multimarker assay with independent prognostic effect on the prediction of survival associated with melanoma in two distinct cohorts.
Kashani-Sabet
Mohammed
M
Auerback Melanoma Research Laboratory and Melanoma Center, Comprehensive Cancer Center, and Departments of Pathology, Surgery, and Urology, University of California-San Francisco, San Francisco, California, USA. kashanim@derm.ucsf.edu
Venna
Suraj
S
Nosrati
Mehdi
M
Rangel
Javier
J
Sucker
Antje
A
Egberts
Friederike
F
Baehner
Frederick L
FL
Simko
Jeff
J
Leong
Stanley P L
SP
Haqq
Chris
C
Hauschild
Axel
A
Schadendorf
Dirk
D
Miller
James R
JR
Sagebiel
Richard W
RW
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis; D008495:Medical Oncology / Q000379:methods; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism*; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012044:Regression Analysis; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor