title: Epithelial-mesenchymal transition (EMT) markers have prognostic impact in multiple primary oral squamous cell carcinoma.
abstract: Multiple primary tumors can occur in up to 35 % of the patients with head and neck cancer, however its clinicopathological features remain controversial. Deregulation of epithelial-mesenchymal transition (EMT) signaling has been associated with aggressive malignancies and tumor progression to metastasis in several cancer types. This study is the first to explore EMT process in multiple primary oral squamous cell carcinomas (OSCC). Immunohistochemical analysis of E-cadherin, catenin (α, β, and γ), APC, collagen IV, Ki-67, cyclin D1, and CD44 were performed in a tissue microarray containing multiple representative areas from 102 OSCC patients followed-up by at least 10 years. Results were analysed in relation to clinicopathological characteristics and survival rates in patients presenting multiple primary tumors versus patients without second primary tumors or metastatic disease. Significant association was observed among multiple OSCCs and protein expression of E-cadherin (P = 0.002), β-catenin (P = 0.047), APC (P = 0.017), and cyclin D1 (P = 0.001) as well as between lymph nodes metastasis and Ki-67 staining (P = 0.021). OSCCs presenting vascular embolization were associated with negative β-catenin membrane expression (P = 0.050). There was a significantly lower survival probability for patients with multiple OSCC (log-rank test, P < 0.0001), for tumors showing negative protein expression for E-cadherin (log-rank test, P = 0.003) and β-catenin (log-rank test, P = 0.031). Stratified multivariate survival analysis revealed a prognostic interdependence of E-cadherin and β-catenin co-downexpression in predicting the worst overall survival (log-rank test, P = 0.007). EMT markers have a predicted value for invasiveness related to multiple primary tumors in OSCC and co-downregulation of E-cadherin and β-catenin has a significant prognostic impact in these cases.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, Segal Cancer Centre and Lady Davis Institute for Medical Research, McGill University, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada, sabrinadaniela@hotmail.com.
authors.forename: Sabrina Daniela
authors.initials: SD
authors.lastname: da Silva
authors.forename: Grégoire B
authors.initials: GB
authors.lastname: Morand
authors.forename: Faisal A
authors.initials: FA
authors.lastname: Alobaid
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hier
authors.forename: Alex M
authors.initials: AM
authors.lastname: Mlynarek
authors.forename: Moulay A
authors.initials: MA
authors.lastname: Alaoui-Jamali
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015820:Cadherins / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D051177:Catenins / Q000096:biosynthesis; D019938:Cyclin D1 / Q000096:biosynthesis; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology*; D009378:Neoplasms, Multiple Primary / Q000401:mortality / Q000473:pathology*; D016612:Paraffin Embedding; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D014021:Tissue Preservation; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D015820:Cadherins; D051177:Catenins; D018960:Hyaluronan Receptors; D019394:Ki-67 Antigen; D051176:beta Catenin; D019938:Cyclin D1