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Lymphocyte antigen 6 superfamily member D is a marker of urothelial and squamous differentiation : Implications for risk stratification of bladder cancer

Andersson, Nina ; Ohlsson, Johan ; Wahlin, Sara LU ; Nodin, Björn LU ; Boman, Karolina LU ; Lundgren, Sebastian LU and Jirström, Karin LU orcid (2020) In Biomarker research 8(1).
Abstract

Background: Screening across a multitude of normal and malignant tissues revealed an enhanced expression of lymphocyte antigen 6 superfamily member D (LY6D) in squamous epithelium and urothelium, as well as in malignancies derived therefrom. The aim of this study was to further delineate the protein expression of LY6D in urothelial bladder cancer, with particular attention to its relationship with clinicopathological characteristics and patient outcome. Methods: Immunohistochemical expression of LY6D was assessed in tissue microarrays with urothelial bladder cancer tumours from three independent patient cohorts; one with transurethral resection of the bladder (TURB) specimens of mixed tumour stages from 110 consecutive cases, one with... (More)

Background: Screening across a multitude of normal and malignant tissues revealed an enhanced expression of lymphocyte antigen 6 superfamily member D (LY6D) in squamous epithelium and urothelium, as well as in malignancies derived therefrom. The aim of this study was to further delineate the protein expression of LY6D in urothelial bladder cancer, with particular attention to its relationship with clinicopathological characteristics and patient outcome. Methods: Immunohistochemical expression of LY6D was assessed in tissue microarrays with urothelial bladder cancer tumours from three independent patient cohorts; one with transurethral resection of the bladder (TURB) specimens of mixed tumour stages from 110 consecutive cases, one with tumours of mixed stages from 260 incident cases in a population-based cohort, and one with paired TURB specimens, resected tumours and a subset of lymph node metastases from 145 patients with muscle-invasive bladder cancer (MIBC). Chi-square and non-parametric tests were applied to examine associations of LY6D expression with clinicopathological characteristics. Kaplan-Meier and Cox regression analyses were applied to examine 5-year overall survival (OS) and recurrence free survival (RFS) in relation to LY6D expression. Results: In the two cohorts with mixed stages, positive LY6D expression was denoted in 63 and 64% of the cases, respectively, and found to be significantly higher in low-grade and less invasive tumours. Negative LY6D expression was significantly associated with a reduced 5-year OS, although not independently of established prognostic factors. In the population-based cohort, LY6D expression was higher in tumours with squamous differentiation and lower in other variant histologies compared to pure urothelial tumours, and the association of LY6D expression with survival was somewhat enhanced after exclusion of the former. LY6D expression was generally lower in the MIBC cohort, and even more reduced in resected tumours compared to TURB specimens in patients who had not received neoadjuvant chemotherapy. There were no significant associations between LY6D expression and RFS, neither allover nor in relation to neoadjuvant chemotherapy. Conclusion: LY6D is a marker of urothelial and squamous differentiation that may add useful diagnostic and prognostic information to better guide the clinical management of bladder cancer, given that the presence of variant histology is taken into account.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Differentiation, Lymphocyte antigen 6 superfamily member D, Prognosis, Urinary bladder cancer, Urothelial cancer
in
Biomarker research
volume
8
issue
1
article number
51
publisher
BioMed Central (BMC)
external identifiers
  • pmid:33042546
  • scopus:85092309414
ISSN
2050-7771
DOI
10.1186/s40364-020-00232-1
language
English
LU publication?
yes
id
24e97a16-f5b9-44bd-be7a-f370a999a38e
date added to LUP
2020-11-02 15:51:01
date last changed
2024-03-20 18:07:54
@article{24e97a16-f5b9-44bd-be7a-f370a999a38e,
  abstract     = {{<p>Background: Screening across a multitude of normal and malignant tissues revealed an enhanced expression of lymphocyte antigen 6 superfamily member D (LY6D) in squamous epithelium and urothelium, as well as in malignancies derived therefrom. The aim of this study was to further delineate the protein expression of LY6D in urothelial bladder cancer, with particular attention to its relationship with clinicopathological characteristics and patient outcome. Methods: Immunohistochemical expression of LY6D was assessed in tissue microarrays with urothelial bladder cancer tumours from three independent patient cohorts; one with transurethral resection of the bladder (TURB) specimens of mixed tumour stages from 110 consecutive cases, one with tumours of mixed stages from 260 incident cases in a population-based cohort, and one with paired TURB specimens, resected tumours and a subset of lymph node metastases from 145 patients with muscle-invasive bladder cancer (MIBC). Chi-square and non-parametric tests were applied to examine associations of LY6D expression with clinicopathological characteristics. Kaplan-Meier and Cox regression analyses were applied to examine 5-year overall survival (OS) and recurrence free survival (RFS) in relation to LY6D expression. Results: In the two cohorts with mixed stages, positive LY6D expression was denoted in 63 and 64% of the cases, respectively, and found to be significantly higher in low-grade and less invasive tumours. Negative LY6D expression was significantly associated with a reduced 5-year OS, although not independently of established prognostic factors. In the population-based cohort, LY6D expression was higher in tumours with squamous differentiation and lower in other variant histologies compared to pure urothelial tumours, and the association of LY6D expression with survival was somewhat enhanced after exclusion of the former. LY6D expression was generally lower in the MIBC cohort, and even more reduced in resected tumours compared to TURB specimens in patients who had not received neoadjuvant chemotherapy. There were no significant associations between LY6D expression and RFS, neither allover nor in relation to neoadjuvant chemotherapy. Conclusion: LY6D is a marker of urothelial and squamous differentiation that may add useful diagnostic and prognostic information to better guide the clinical management of bladder cancer, given that the presence of variant histology is taken into account. </p>}},
  author       = {{Andersson, Nina and Ohlsson, Johan and Wahlin, Sara and Nodin, Björn and Boman, Karolina and Lundgren, Sebastian and Jirström, Karin}},
  issn         = {{2050-7771}},
  keywords     = {{Differentiation; Lymphocyte antigen 6 superfamily member D; Prognosis; Urinary bladder cancer; Urothelial cancer}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Biomarker research}},
  title        = {{Lymphocyte antigen 6 superfamily member D is a marker of urothelial and squamous differentiation : Implications for risk stratification of bladder cancer}},
  url          = {{http://dx.doi.org/10.1186/s40364-020-00232-1}},
  doi          = {{10.1186/s40364-020-00232-1}},
  volume       = {{8}},
  year         = {{2020}},
}