ABSTRACT
BACKGROUND: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis. OBJECTIVE: To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management. METHODS: Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n = 586) were collected from 23 independent centers in a prospectively designed study. A GEP signature was developed using a discovery cohort (n = 202) and validated in a separate, nonoverlapping, independent cohort (n = 324). RESULTS: A prognostic 40-GEP test was developed and validated, stratifying patients with high-risk cSCC into classes based on metastasis risk: class 1 (low risk), class 2A (high risk), and class 2B (highest risk). For the validation cohort, 3-year metastasis-free survival rates were 91.4%, 80.6%, and 44.0%, respectively. A positive predictive value of 60% was achieved for the highest-risk group (class 2B), an improvement over staging systems, and negative predictive value, sensitivity, and specificity were comparable to staging systems. LIMITATIONS: Potential understaging of cases could affect metastasis rate accuracy. CONCLUSION: The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/secondary , Gene Expression Profiling/methods , Skin Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging/methods , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Assessment/methods , Skin/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/epidemiology , Skin Neoplasms/genetics , Survival RateABSTRACT
OBJECTIVE: To assess the efficacy of intraincisional clindamycin therapy as an alternative to nafcillin treatment in decreasing the risk of postoperative wound infections in dermatologic surgery. DESIGN: Prospective, double-blinded, randomized, placebo-controlled trial conducted over a 7-month period. SETTING: Three private practice Mohs micrographic surgery referral centers. PATIENTS: A total of 1030 consecutive patients who underwent Mohs micrographic surgery with subsequent reconstruction. INTERVENTIONS: Prior to reconstruction, patients were randomly assigned to receive either intraincisional buffered lidocaine with epinephrine containing clindamycin or buffered lidocaine with epinephrine without clindamycin. Nurses and physicians who scored the wound at follow-up were blinded to the treatment conditions. MAIN OUTCOME MEASURES: Surgical wounds evaluated at the time of suture removal were scored according to a standardized assessment based on erythema, edema, and the presence of purulent discharge. Wounds scored 4 or higher were considered to be infected. Bacterial cultures obtained when indicated were also compared. RESULTS: Of the 1172 surgical wounds included in the study, 29 had wound scores of 4 or higher, 6 in the study group and 23 in the control group (P =.001, Fisher exact test). Of these 29, 18 had culture-positive infections. Four of these occurred in the study group, and 14 occurred in the control group (P =.02, Fisher exact test). CONCLUSIONS: The results of this study further support the efficacy of single-dose preoperative intraincisional antibiotic treatment for dermatologic surgery. With the relatively high prevalence of patient-reported penicillin allergies, buffered lidocaine containing clindamycin offers an inexpensive, safe, convenient, and effective alternative.
