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Cortactin and phosphorylated cortactin tyr421 and tyr466 expression in supraglottic laryngeal carcinomas and lymph node metastases

Abstract

Background

The most important adverse prognostic factor for laryngeal squamous cell carcinoma (LSCC) is the presence of cervical lymph node metastases. The supraglottic area of the larynx is richly supplied with lymphatics, and 25%-75% of supraglottic carcinomas metastasize in neck lymph nodes. Cortactin is a multidomain protein related to actin cytoskeleton regulation, podosome and lamellipodia formation, integrin signaling, axon guidance and extracellular matrix degradation. Cortactin is involved in metastasis formation because of its role in cell mobility. The present study focused mainly on the role of cortactin and phosphorylated cortactin (residues tyr421 and tyr466) expression and subcellular localization in primary supraglottic LSCCs and their cervical lymph node metastases.

Methods

The immunohistochemical expression of cortactin, p-Y466-cortactin and p-Y421-cortactin was assessed in 38 primary supraglottic LSCCs and 10 lymph node metastases. The statistical approach included bootstrapping analysis.

Results

Despite a significantly higher expression of cortactin in carcinoma cells than in adjacent normal laryngeal mucosa, no associations emerged between prognosis and the expression of cortactin or its isoforms in supraglottic LSCC. Statistical analysis found cortactin expression higher in less-differentiated LSCCs (p = 0.03). A significant direct correlation was found between cortactin and p-Y466-cortactin levels (p = 0.031), and between p-Y466-cortactin and p-Y421-cortactin levels (p = 0.001).

Conclusions

Cortactin expression in carcinoma cells and its known involvement in the EGFR pathway suggest a role for this protein as a target for LSCC therapy. Further prospective studies are needed to investigate the potential of cortactin, p-Y466-cortactin and p-Y421-cortactin expression as markers of response to treatment (particularly EGFR-directed agents) in LSCC.

Post author correction

Article Type: ORIGINAL RESEARCH ARTICLE

DOI:10.5301/ijbm.5000297

Authors

Gino Marioni, Marco Lionello, Rosario Marchese-Ragona, Elena Fasanaro, Elisa Valentini, Elisabetta Zanoletti, Paola Stritoni, Giulia Ramacciotti, Vincenza Guzzardo, Luciano Giacomelli, Giovanni Ralli, Giancarlo Ottaviano, Stella Blandamura

Article History

Disclosures

Financial support: This study was partly supported by grant no. 60A07-4802/15 (to G.M.) from the University of Padova, Italy.
Conflict of interest: The authors declare that they have no conflict of interest.

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Authors

Affiliations

  •  Department of Neurosciences, Otolaryngology Section, University of Padua, Padua - Italy
  •  Otolaryngology Unit, Vittorio Veneto Hospital, Vittorio Veneto - Italy
  •  Department of Radiotherapy, Veneto Institute of Oncology IOV–IRCCS, Padua - Italy
  •  Department of Medicine DIMED, University of Padua, Padua - Italy
  •  Department of Otolaryngology–Head and Neck Surgery, VU University Medical Center, Amsterdam - The Netherlands
  •  Department of Sensory Organs, Policlinico Umberto I, Sapienza University of Rome, Rome - Italy

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