PMID- 28885660 OWN - NLM STAT- MEDLINE DCOM- 20180831 LR - 20181202 IS - 1724-6008 (Electronic) IS - 0393-6155 (Linking) VI - 33 IP - 1 DP - 2018 Jan TI - Cortactin and phosphorylated cortactin tyr(421) and tyr(466) expression in supraglottic laryngeal carcinomas and lymph node metastases. PG - 79-86 LID - 10.5301/ijbm.5000297 [doi] AB - 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 tyr(421) and tyr(466)) 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. FAU - Marioni, Gino AU - Marioni G AD - 1 Department of Neurosciences, Otolaryngology Section, University of Padua, Padua - Italy. FAU - Lionello, Marco AU - Lionello M AD - 2 Otolaryngology Unit, Vittorio Veneto Hospital, Vittorio Veneto - Italy. FAU - Marchese-Ragona, Rosario AU - Marchese-Ragona R AD - 1 Department of Neurosciences, Otolaryngology Section, University of Padua, Padua - Italy. FAU - Fasanaro, Elena AU - Fasanaro E AD - 3 Department of Radiotherapy, Veneto Institute of Oncology IOV-IRCCS, Padua - Italy. FAU - Valentini, Elisa AU - Valentini E AD - 4 Department of Medicine DIMED, University of Padua, Padua - Italy. FAU - Zanoletti, Elisabetta AU - Zanoletti E AD - 1 Department of Neurosciences, Otolaryngology Section, University of Padua, Padua - Italy. FAU - Stritoni, Paola AU - Stritoni P AD - 1 Department of Neurosciences, Otolaryngology Section, University of Padua, Padua - Italy. FAU - Ramacciotti, Giulia AU - Ramacciotti G AD - 1 Department of Neurosciences, Otolaryngology Section, University of Padua, Padua - Italy. AD - 5 Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Amsterdam - The Netherlands. FAU - Guzzardo, Vincenza AU - Guzzardo V AD - 4 Department of Medicine DIMED, University of Padua, Padua - Italy. FAU - Giacomelli, Luciano AU - Giacomelli L AD - 4 Department of Medicine DIMED, University of Padua, Padua - Italy. FAU - Ralli, Giovanni AU - Ralli G AD - 6 Department of Sensory Organs, Policlinico Umberto I, Sapienza University of Rome, Rome - Italy. FAU - Ottaviano, Giancarlo AU - Ottaviano G AD - 1 Department of Neurosciences, Otolaryngology Section, University of Padua, Padua - Italy. FAU - Blandamura, Stella AU - Blandamura S AD - 4 Department of Medicine DIMED, University of Padua, Padua - Italy. LA - eng PT - Journal Article PL - United States TA - Int J Biol Markers JT - The International journal of biological markers JID - 8712411 RN - 0 (Biomarkers, Tumor) RN - 0 (Cortactin) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adult MH - Aged MH - Biomarkers, Tumor/genetics MH - Carcinoma/*genetics/pathology MH - Cortactin/*genetics MH - ErbB Receptors/*genetics MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Laryngeal Neoplasms/*genetics/pathology MH - Lymph Nodes/pathology MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Phosphorylation MH - Prognosis OTO - NOTNLM OT - Cortactin OT - Laryngeal OT - Lymph node metastases OT - Phosphorylated OT - Squamous cell carcinoma OT - Supraglottic EDAT- 2017/09/09 06:00 MHDA- 2018/09/01 06:00 CRDT- 2017/09/09 06:00 PHST- 2017/09/09 06:00 [pubmed] PHST- 2018/09/01 06:00 [medline] PHST- 2017/09/09 06:00 [entrez] AID - D9AC40DA-438E-4FD1-ACCA-A2FF40630FB5 [pii] AID - 10.5301/ijbm.5000297 [doi] PST - ppublish SO - Int J Biol Markers. 2018 Jan;33(1):79-86. doi: 10.5301/ijbm.5000297.