title: Validation and Enhancement of the Clinicopathological Melanoma Nomogram via Incorporation of a Molecular Marker in the Primary Tumor.
abstract: To validate the melanoma nomogram and improve its function in prediction of nodal dissemination by incorporating a molecular marker in the model. Microphthalmia transcription factor (MITF) is an important regulator of melanocyte homeostasis and differentiation. We have shown that the grade of MITF expression in primary melanoma cells can serve as a predictor of nodal status. Many efforts to identify the nodal spread in cutaneous melanoma using non-invasive means have been recently undertaken. A nomogram was developed by Memorial Sloan Kettering Cancer Center (MSKCC) based on clinicopathological features of the primary melanoma to predict the nodal status. In this study, we applied the same nomogram for external validation. Then, we added MITF as an independent predictive factor, and assessed its impact on the nomogram's accuracy in prediction of the nodal spread.
  
  
  
  We included 171 patients with melanoma with available tumor specimens, and used MITF staining grade of ≥50% as a pathological characteristic of the primary tumor in addition to age, location, thickness, Clark level, and ulceration, as reported by MSKCC.
  
  
  
  Upon comparison of receiver operating curves, we confirmed the external validation of the melanoma nomogram, in accordance with the MSKCC curves [area under the curve (AUC) 0.742 vs. 0.650]. Addition of MITF ≥50% as an independent factor in the analysis improved the model fit significantly (AUC=0.825 vs. 0.742; p<0.0001).
  
  
  
  The nomogram described by MSKCC is a valuable tool in predicting sentinel lymph node involvement in primary cutaneous melanoma. Addition of MITF≥50% into the logistic regression analysis significantly improves the accuracy of the melanoma nomogram in prediction of regional nodal spread.
authors.affiliation: Department of General Surgery, University of Illinois Hospital and Health Sciences System, Chicago, IL, U.S.A. snaffouj@uic.edu.
authors.forename: Samer A
authors.initials: SA
authors.lastname: Naffouje
authors.affiliation: Department of Internal Medicine, Louis Weiss Memorial Hospital, Chicago, IL, U.S.A.
authors.forename: Rand
authors.initials: R
authors.lastname: Naffouje
authors.affiliation: Department of Biostatistics, University of Illinois at Chicago College of Medicine, Chicago, IL, U.S.A.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Surgical Oncology, University of Illinois at Chicago Hospital and Health Sciences System, Chicago, IL, U.S.A.
authors.forename: George I
authors.initials: GI
authors.lastname: Salti
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor
keywords: Microphthalmia transcription factor; melanoma; nomogram