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Prognostic value and clinicopathologic characteristics of L1 cell adhesion molecule (L1CAM) in a large series of vulvar squamous cell carcinomas
BACKGROUND: Vulvar cancer treatment is mostly curative, but also has high morbidity rates. In a search for markers that can identify patients at risk of metastases, we investigated the prognostic value of L1-cell adhesion molecule (L1CAM) in large series of vulvar squamous cell carcinomas (VSCCs). L...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041974/ https://www.ncbi.nlm.nih.gov/pubmed/27028855 http://dx.doi.org/10.18632/oncotarget.8353 |
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author | Trietsch, Marjolijn D. Oonk, Maaike H.M. Hawinkels, Lukas J.A.C. Bor, Rosalie van Eendenburg, Jaap D.H. Ivanova, Zina Peters, Alexander A.W. Nijman, Hans W. Gaarenstroom, Katja N. Bosse, Tjalling |
author_facet | Trietsch, Marjolijn D. Oonk, Maaike H.M. Hawinkels, Lukas J.A.C. Bor, Rosalie van Eendenburg, Jaap D.H. Ivanova, Zina Peters, Alexander A.W. Nijman, Hans W. Gaarenstroom, Katja N. Bosse, Tjalling |
author_sort | Trietsch, Marjolijn D. |
collection | PubMed |
description | BACKGROUND: Vulvar cancer treatment is mostly curative, but also has high morbidity rates. In a search for markers that can identify patients at risk of metastases, we investigated the prognostic value of L1-cell adhesion molecule (L1CAM) in large series of vulvar squamous cell carcinomas (VSCCs). L1CAM promotes cell motility and is an emerging prognostic factor for metastasis in many cancer subtypes. RESULTS: L1CAM expression was observed at the invasive front or in spray-patterned parts of 17% of the tumours. L1CAM-positive tumours expressed vimentin more often, but L1CAM expression was not associated with TP53 or CTNNB1 mutations. Five-year survival was worse for patients with L1CAM expression (overall survival 46.1% vs 63.6%, P=.014, disease specific survival 63.8% vs 80.0%, P=.018). Multivariate analysis indicates L1CAM expression as an independent prognostic marker (HR 2.9, 95% CI 1.10–7.68). An in vitro spheroid invasion assay showed decreased invasion of L1CAM-expressing VSCC spindle cells after treatment with L1CAM-neutralising antibodies. MATERIALS AND METHODS: Paraffin-embedded tumour tissue from two cohorts (N=103 and 245) of primary VSCCs were stained for L1CAM, vimentin and E-cadherin. Patients of the first cohort were tested for human papilloma virus infection and sequenced for TP53 and CTNNB1 (β-catenin) mutations. The expression of L1CAM was correlated to clinical characteristics and patient survival. CONCLUSION: This is the first study to show high L1CAM-expression at the infiltrating margin of VSCC's. L1CAM-expressing VSCCs had a significantly worse prognosis compared to L1CAM-negative tumours. The highest expression was observed in spindle-shaped cells, where it might be correlated to their invasive capacity. |
format | Online Article Text |
id | pubmed-5041974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50419742016-10-10 Prognostic value and clinicopathologic characteristics of L1 cell adhesion molecule (L1CAM) in a large series of vulvar squamous cell carcinomas Trietsch, Marjolijn D. Oonk, Maaike H.M. Hawinkels, Lukas J.A.C. Bor, Rosalie van Eendenburg, Jaap D.H. Ivanova, Zina Peters, Alexander A.W. Nijman, Hans W. Gaarenstroom, Katja N. Bosse, Tjalling Oncotarget Research Paper BACKGROUND: Vulvar cancer treatment is mostly curative, but also has high morbidity rates. In a search for markers that can identify patients at risk of metastases, we investigated the prognostic value of L1-cell adhesion molecule (L1CAM) in large series of vulvar squamous cell carcinomas (VSCCs). L1CAM promotes cell motility and is an emerging prognostic factor for metastasis in many cancer subtypes. RESULTS: L1CAM expression was observed at the invasive front or in spray-patterned parts of 17% of the tumours. L1CAM-positive tumours expressed vimentin more often, but L1CAM expression was not associated with TP53 or CTNNB1 mutations. Five-year survival was worse for patients with L1CAM expression (overall survival 46.1% vs 63.6%, P=.014, disease specific survival 63.8% vs 80.0%, P=.018). Multivariate analysis indicates L1CAM expression as an independent prognostic marker (HR 2.9, 95% CI 1.10–7.68). An in vitro spheroid invasion assay showed decreased invasion of L1CAM-expressing VSCC spindle cells after treatment with L1CAM-neutralising antibodies. MATERIALS AND METHODS: Paraffin-embedded tumour tissue from two cohorts (N=103 and 245) of primary VSCCs were stained for L1CAM, vimentin and E-cadherin. Patients of the first cohort were tested for human papilloma virus infection and sequenced for TP53 and CTNNB1 (β-catenin) mutations. The expression of L1CAM was correlated to clinical characteristics and patient survival. CONCLUSION: This is the first study to show high L1CAM-expression at the infiltrating margin of VSCC's. L1CAM-expressing VSCCs had a significantly worse prognosis compared to L1CAM-negative tumours. The highest expression was observed in spindle-shaped cells, where it might be correlated to their invasive capacity. Impact Journals LLC 2016-03-25 /pmc/articles/PMC5041974/ /pubmed/27028855 http://dx.doi.org/10.18632/oncotarget.8353 Text en Copyright: © 2016 Trietsch et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Trietsch, Marjolijn D. Oonk, Maaike H.M. Hawinkels, Lukas J.A.C. Bor, Rosalie van Eendenburg, Jaap D.H. Ivanova, Zina Peters, Alexander A.W. Nijman, Hans W. Gaarenstroom, Katja N. Bosse, Tjalling Prognostic value and clinicopathologic characteristics of L1 cell adhesion molecule (L1CAM) in a large series of vulvar squamous cell carcinomas |
title | Prognostic value and clinicopathologic characteristics of L1 cell adhesion molecule (L1CAM) in a large series of vulvar squamous cell carcinomas |
title_full | Prognostic value and clinicopathologic characteristics of L1 cell adhesion molecule (L1CAM) in a large series of vulvar squamous cell carcinomas |
title_fullStr | Prognostic value and clinicopathologic characteristics of L1 cell adhesion molecule (L1CAM) in a large series of vulvar squamous cell carcinomas |
title_full_unstemmed | Prognostic value and clinicopathologic characteristics of L1 cell adhesion molecule (L1CAM) in a large series of vulvar squamous cell carcinomas |
title_short | Prognostic value and clinicopathologic characteristics of L1 cell adhesion molecule (L1CAM) in a large series of vulvar squamous cell carcinomas |
title_sort | prognostic value and clinicopathologic characteristics of l1 cell adhesion molecule (l1cam) in a large series of vulvar squamous cell carcinomas |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041974/ https://www.ncbi.nlm.nih.gov/pubmed/27028855 http://dx.doi.org/10.18632/oncotarget.8353 |
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