RSPO2 is a novel sensitive and specific biomarker in esophageal squamous intraepithelial neoplasia

Abstract Background: Esophageal squamous intraepithelial neoplasia (ESIN) is considered a precursor lesion of esophageal squamous cell carcinoma (ESCC), High grade ESIN (HGESIN)has much higher risk of progression to ESCC comparing with low grade ESIN(LGESIN). the distinction between squamous cell dysplasia and reactive changes, and HGESIN and LGESIN can sometimes be subjective and challenging. RSPO2 is a member of the R-spondin family of proteins, and was identified as either oncogenes or tumor suppressors depending on the cancer type. Methods: In the current study, we compared the immunohistochemistry(IHC) expression of newly identified marker RSPO2 with p53 and Ki-67 in different esophageal squamous lesions, and to evaluate correlations between their expression levels in these lesions. Results: IHC stains of RSPO2, p53 and Ki-6 were performed on endoscopic submucosal dissection specimens from 71 patients including 96 HGESIN, 50 LGESIN, and 160 fragments of adjacent normal squamous esophageal mucosa. RSPO2 and Ki-67 showed high sensitivity and specificity for diagnosing ESIN from normal squamous epithelium. The sensitivity of high level expression of RSPO2 in distinguishing HGESIN from LGESIN was as high as 97.92%, but specificity was only 72%. The specificity of strong staining of RSPO2 in distinguishing HGESIN from LGESIN was as high as 100%, but the sensitivity was as low as 29.17%. The specificity of high level expression of Ki-67 and p53 in distinguishing HGESIN from LGESIN was 96% and 96% respectively, but sensitivity was reduced to 56.25% and 62.5% respectively. Conclusions: This study demonstrates that both RSPO2 and Ki-67 can be useful in differential diagnosing ESIN.