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Open AccessArticle

Y Chromosome Loss Is a Frequent Event in Barrett’s Adenocarcinoma and Associated with Poor Outcome

1
Institute of Pathology, University Hospital Cologne, 50937 Cologne, Germany
2
Department of General, Visceral and Cancer Surgery, University Hospital Cologne, 50937 Cologne, Germany
3
Department of Internal Medicine I, University of Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, 50937 Cologne, Germany
*
Author to whom correspondence should be addressed.
Contributed equally to the work.
Cancers 2020, 12(7), 1743; https://doi.org/10.3390/cancers12071743 (registering DOI)
Received: 26 April 2020 / Revised: 23 June 2020 / Accepted: 26 June 2020 / Published: 30 June 2020
Background: The loss of the Y chromosome in various malignant diseases has been described previously. There are no reliable information on the actual frequency, significance and homogeneity of Y chromosome loss (LoY) in esophageal adenocarcinoma (EAC). Methods: 400 male EAC including lymph-node metastases were analyzed with commercially available Y chromosome specific fluorescence in-situ probes. The results were correlated with molecular and immunohistochemical markers and clinicopathological aspects. Results: The entire cohort (n = 400) showed a singular LoY of one chromosome arm in 1.0% (q-arm) and 2.8% (p-arm), complete LoY in 52.5%. LoY was strongly associated with shortened overall-survival (OS). Patients with preserved Y chromosome had a median OS of 58.8 months, patients with LoY an OS of 19.4 months (p < 0.001). Multivariate analysis showed LoY as an independent prognostic marker with a hazard ratio of 1.835 (95% CI 1.233–2.725). LoY correlated with TP53 mutations (p = 0.003), KRAS amplification (p = 0.004), loss of ARID1a (p = 0.045) and presence of LAG3 (p = 0.018). Conclusions: Loss of the Y chromosome is a very common phenomenon in EAC. The LoY is heterogeneously distributed within the tumor, but corresponding lymph node metastases frequently show homogeneous LoY, indicating a selection and metastasizing advantage with poor prognosis. To date, the male predominance of EAC (7–9:1) is unclear, so genetic explanatory models are favored. The LoY in EAC may be biologically and functionally relevant and additional genomic or functional analyses are needed. View Full-Text
Keywords: Y chromosome loss; Barrett; esophageal adenocarcinoma; prognosis; tumor microenvironment Y chromosome loss; Barrett; esophageal adenocarcinoma; prognosis; tumor microenvironment
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Loeser, H.; Wölwer, C.B.; Alakus, H.; Chon, S.-H.; Zander, T.; Buettner, R.; Hillmer, A.M.; Bruns, C.J.; Schroeder, W.; Gebauer, F.; Quaas, A. Y Chromosome Loss Is a Frequent Event in Barrett’s Adenocarcinoma and Associated with Poor Outcome. Cancers 2020, 12, 1743.

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