Loss of Y chromosome in male patients with esophageal adenocarcinoma is associated with shortened overall-survival

Background Esophageal adenocarinoma (EAC) is more prevalent in men than women (9:1) and this disparity cannot be fully explained by known risk factors. Recent studies have shown that loss of Y chromosome (LoY) confers an increased risk of solid cancer and reduces life expectancy in men.

Methods For evaluation of Y-chromosome we performed flourescence in situ hybridization (FISH) with two Y-specific probes (Abbott Molecular, Germany) for the long (q12; green signal) and the short arm (p11.3; orange signal). No green and orange signals were defined as loss of the Y-chromosome. Detection of either green or orange signals was defined as mosaic loss of the Y-chromosome. On slide non-tumor cells served as internal control.

Results Singular LoY of one chromosome arms was present in 3.9 % (q-arm) and 1.3 % (p-arm)., total LoY in 55.7 %. Patients age or administration of neoadjuvant therapy was not associated with LoY. Loss of any Y chromosomal part is associated with advanced tumor stages (pN+ p < 0.001) and advanced UICC stages (p < 0.001). Correlation with molecular marker shows a correlation between LoY and TP53 mutations (p = 0.008). Patients with LoY show a shortened overall-survival (OS) in Kaplan Meier survival analysis. Median OS is 19.4 months in LoY group compared to 58.1 months in the control group (p < 0.001). The survival difference is also detectable if only one arm of Y chromosome is deleted.

Discussion This is the first analysis of LoY in EAC in a large patients cohort so far. There is a clear connection between the loss of the Y chromosome and overall survival. The cause or timing of Y chromosome loss during tumor progression is unknown. Similar results have been shown for tumors of the neck and head area and prostate carcinomas.

Publikationsverlauf

Artikel online veröffentlicht:
07. September 2021