The expression and prognostic relevance of CDH3 in tongue squamous cell carcinoma

doi:10.1111/apm.13176

. 2021 Dec;129(12):717-728.

doi: 10.1111/apm.13176. Epub 2021 Nov 3.

The expression and prognostic relevance of CDH3 in tongue squamous cell carcinoma

Miia Seppälä¹, Laura Jauhiainen¹, Sanni Tervo², Ahmed Al-Samadi^{1

3}, Markus Rautiainen⁴, Tuula Salo^{3

5

6

7

8}, Kaisa Lehti^{9

10}, Outi Monni¹¹, Sampsa Hautaniemi¹², Olli Tynninen¹³, Antti Mäkitie^{14

15

16}, Laura K Mäkinen¹⁷, Timo Paavonen¹⁸, Sanna Toppila-Salmi¹⁹

Affiliations

¹ Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland.
² Department of Pathology, University of Tampere, Tampere, Finland.
³ Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴ Department of Otorhinolaryngology, Tampere University Hospital, Tampere, Finland.
⁵ Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁶ Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.
⁷ Medical Research Centre, Oulu University Hospital, Oulu, Finland.
⁸ Helsinki University Hospital, Helsinki, Finland.
⁹ Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
¹⁰ Department of Microbiology, Tumor, and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
¹¹ Applied Tumor Genomics Research Program, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
¹² Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland.
¹³ Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland.
¹⁴ Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
¹⁵ Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki, HUS Helsinki University Hospital, Helsinki, Finland.
¹⁶ Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
¹⁷ Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
¹⁸ Department of Pathology, Fimlab Laboratories and Department of Medicine and Health Technology, Tampere University, Tampere, Finland.
¹⁹ Skin and Allergy Hospital, Helsinki University Hospital, Haartman Institute University of Helsinki, University of Helsinki, Helsinki, Finland.

PMID: 34580913
DOI: 10.1111/apm.13176

The expression and prognostic relevance of CDH3 in tongue squamous cell carcinoma

Miia Seppälä et al. APMIS. 2021 Dec.

. 2021 Dec;129(12):717-728.

doi: 10.1111/apm.13176. Epub 2021 Nov 3.

Authors

Affiliations

¹ Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland.
² Department of Pathology, University of Tampere, Tampere, Finland.
³ Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴ Department of Otorhinolaryngology, Tampere University Hospital, Tampere, Finland.
⁵ Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁶ Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.
⁷ Medical Research Centre, Oulu University Hospital, Oulu, Finland.
⁸ Helsinki University Hospital, Helsinki, Finland.
⁹ Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
¹⁰ Department of Microbiology, Tumor, and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
¹¹ Applied Tumor Genomics Research Program, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
¹² Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland.
¹³ Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland.
¹⁴ Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
¹⁵ Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki, HUS Helsinki University Hospital, Helsinki, Finland.
¹⁶ Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
¹⁷ Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
¹⁸ Department of Pathology, Fimlab Laboratories and Department of Medicine and Health Technology, Tampere University, Tampere, Finland.
¹⁹ Skin and Allergy Hospital, Helsinki University Hospital, Haartman Institute University of Helsinki, University of Helsinki, Helsinki, Finland.

PMID: 34580913
DOI: 10.1111/apm.13176

Abstract

P-cadherin (CDH3) is a cell-to-cell adhesion molecule that regulates several cellular homeostatic processes in normal tissues. Lack of CDH3 expression is associated with aggressive behavior in oral squamous cell carcinoma (OSCC). Previous studies have shown that CDH3 is downregulated in high-grade OSCC and its reduced expression is predictive for poorer survival. The aim of this study was to evaluate the expression and prognostic relevance of CDH3 in tongue squamous cell carcinoma (TSCC). A retrospective series of 211 TSCC and 50 lymph node samples were stained immunohistochemically with polyclonal antibody (anti-CDH3). CDH3 expression was assessed semi-quantitatively with light microscopy. Fisher's exact test was used to compare patient and tumor characteristics, and the correlations were tested by Spearman correlation. Survival curves were drawn by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate Cox regression was used to estimate the association between CDH3 expression and survival. CDH3 expression did not affect TSCC patient's disease-specific survival or overall survival. Strong CDH3 expression in the primary tumor predicted poor disease-specific and overall survival in patients with recurrent disease. CDH3 expression in lymph nodes without metastasis was negative in all cases. CDH3 expression was positive in all lymph node metastases with extranodal extension. In contrast to previous report about the prognostic value of CDH3 in OSCC, we were not able to validate the result in TSCC.

Keywords: CDH3; immunohistochemistry; lymph node metastasis; survival; tongue squamous cell carcinoma.

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References

REFERENCES

1. Leemans CR, Braakhuis BJM, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer 2010;11:9-22.
1. Scully C, Bagan J. Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications. Oral Dis 2009;15:388-99. https://doi.org/10.1111/j.1601-0825.2009.01563.x
1. Mäkitie AA, Koivunen P, Keski-Säntti H, et al. Oral tongue carcinoma and its treatment in Finland. Eur Arch Otorhinolaryngol 2007;264:263-7.
1. Bello IO, Soini Y, Salo T. Prognostic evaluation of oral tongue cancer: means, markers and perspectives (II). Oral Oncol 2010;46:636-43.
1. Abraham R, Schafer J, Rothe M, Bange J, Knyazev P, Ullrich A. Identification of MMP-15 as an anti-apoptotic factor in cancer cells. J Biol Chem 2005;280:34123-32.

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[1] Leemans CR, Braakhuis BJM, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer 2010;11:9-22.

[2] Leemans CR, Braakhuis BJM, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer 2010;11:9-22.

[3] Scully C, Bagan J. Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications. Oral Dis 2009;15:388-99. https://doi.org/10.1111/j.1601-0825.2009.01563.x

[4] Scully C, Bagan J. Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications. Oral Dis 2009;15:388-99. https://doi.org/10.1111/j.1601-0825.2009.01563.x

[5] Mäkitie AA, Koivunen P, Keski-Säntti H, et al. Oral tongue carcinoma and its treatment in Finland. Eur Arch Otorhinolaryngol 2007;264:263-7.

[6] Mäkitie AA, Koivunen P, Keski-Säntti H, et al. Oral tongue carcinoma and its treatment in Finland. Eur Arch Otorhinolaryngol 2007;264:263-7.

[7] Bello IO, Soini Y, Salo T. Prognostic evaluation of oral tongue cancer: means, markers and perspectives (II). Oral Oncol 2010;46:636-43.

[8] Bello IO, Soini Y, Salo T. Prognostic evaluation of oral tongue cancer: means, markers and perspectives (II). Oral Oncol 2010;46:636-43.

[9] Abraham R, Schafer J, Rothe M, Bange J, Knyazev P, Ullrich A. Identification of MMP-15 as an anti-apoptotic factor in cancer cells. J Biol Chem 2005;280:34123-32.

[10] Abraham R, Schafer J, Rothe M, Bange J, Knyazev P, Ullrich A. Identification of MMP-15 as an anti-apoptotic factor in cancer cells. J Biol Chem 2005;280:34123-32.

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The expression and prognostic relevance of CDH3 in tongue squamous cell carcinoma

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The expression and prognostic relevance of CDH3 in tongue squamous cell carcinoma

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