In:
Cancers, MDPI AG, Vol. 12, No. 7 ( 2020-06-30), p. 1743-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2072-6694
DOI:
10.3390/cancers12071743
Language:
English
Publisher:
MDPI AG
Publication Date:
2020
detail.hit.zdb_id:
2527080-1
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