Research Papers:

Prognostic value and clinicopathologic characteristics of L1 cell adhesion molecule (L1CAM) in a large series of vulvar squamous cell carcinomas

Marjolijn D. Trietsch _, Maaike H.M. Oonk, Lukas J.A.C. Hawinkels, Rosalie Bor, Jaap D.H. van Eendenburg, Zina Ivanova, Alexander A.W. Peters, Hans W. Nijman, Katja N. Gaarenstroom and Tjalling Bosse

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Oncotarget. 2016; 7:26192-26205. https://doi.org/10.18632/oncotarget.8353

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Marjolijn D. Trietsch1, Maaike H.M. Oonk2, Lukas J.A.C. Hawinkels3, Rosalie Bor3, Jaap D.H. van Eendenburg1, Zina Ivanova4, Alexander A.W. Peters5, Hans W. Nijman2, Katja N. Gaarenstroom5, Tjalling Bosse1

1Department of Pathology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands

2Department of Gynaecology, University Medical Center Groningen, 9700 RB Groningen, The Netherlands

3Gastroenterology-Hepatology and Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands

4Institute for Pathology and Parasitology, Bulgarian Academy of Sciences, 1040 Sofia, Bulgaria

5Department of Gynaecology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Correspondence to:

Marjolijn D. Trietsch, e-mail: [email protected]

Keywords: L1 cell adhesion molecule, L1CAM, vulvar cancer, squamous cell carcinoma, survival

Received: December 31, 2015    Accepted: March 04, 2016    Published: March 25, 2016


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.

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