Three-gene immunohistochemical panel predicts progression and unfavorable prognosis in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is a highly invasive disease with a poor long-term survival rate. Although there has been progress in understanding the pathogenesis of ESCC, there are currently no molecular biomarkers that are used in routine clinical practices to determine prognosis. Therefore, the aim of this study was to determine a small immunohistochemical panel that could predict the prognosis of patients with ESCC. Phospholipase C epsilon-1 (PLCE1), IKKα, IKBα, p65, and p53 were highly expressed in ESCC tissues. The high expression level of PLCE1, IKBα, and p53 showed a significant positive correlation with a short overall survival (P = .022, .009, and .024, respectively). This 3-biomarker panel (ie, PLCE1, IKBα, and p53) was found to be a predictor of ESCC, with a worse overall survival as each positive marker was added (hazard ratio, 1.553; 95% confidence interval, 1.166-2.067; P = .003). In another cohort (including 1922 esophageal endoscopic biopsy tissues), the lesions of 28 patients were aggravated. Three proteins (PLCE1, 12/28 [42.86%]; IKBα, 16/28 [57.14%]; p53, 16/28 [57.14%]) were immunoreactive in patients with progressive disease. Our study identified and validated that this immunohistochemical biomarker panel of 3 proteins, consisting of PLCE1, IKBα, and p53, is not only independently associated with an unfavorable outcome for ESCC patients but also able to predict disease progression to precancerous lesions.