Combined score of Y chromosome loss and T-cell infiltration improves UICC based stratification of esophageal adenocarcinoma

Abstract

Background: Staging, especially clinical lymph node staging in esophageal adenocarcinoma has only moderate sensitivity and specificity. Therefore, we evaluated combined molecular markers to predict prognosis.

Patients and methods: 890 tumor tissue samples were obtained from patients who underwent surgery for esophageal adenocarcinoma with curative intent. These were stained by tissue micro array for 48 markers which are associated with tumorigenesis and correlated with clinical data (TNM-staging, overall survival) by multivariate Cox regression.

Results: Two markers (preserved Y chromosome and high grade of (CD3+) T-cell infiltration) were found to be significantly and independently associated with better overall survival. We formed a score (called CY score) from the two markers. The more markers are positive and thus the higher the score (ranging from 0 to 2), the better the overall survival, independently of UICC. Moreover, we developed a combination score of the UICC and CY score based on cluster analysis. Patients with a UICC stage of III with the presence of both traits (CY=2) can be assigned to a better prognosis group (group II), whereas patients with a UICC stage of I without both traits (CY=0) must be assigned to a worse prognosis group (group II). Therefore, patients in stage I with adverse molecular signature might benefit of multimodal therapy.

Conclusion: In summary, the CY score adds prognostic information to the UICC stage based on tumor biology in esophageal adenocarcinoma and warrants further evaluations in independent clinical cohorts.

Keywords: CD3 cell infiltration; UICC staging; Y chromosome loss; esophageal adenocarcinoma; prognosis.