title: Downregulation of CD9 protein expression is associated with aggressive behavior of oral squamous cell carcinoma.
abstract: Squamous cell carcinoma of the oral cavity (OSCC) is a malignancy characterized by a high degree of local aggression and metastasis to cervical lymph nodes. Tetraspanins are proteins with functional roles in a wide array of cellular processes and are reported to be associated with tumor progression. The present study investigated the expression of the CD9, CD37, CD63, CD81 and CD82 tetraspanins in OSCC using immunohistochemistry (IHC) and quantitative Real Time-PCR (qRT-PCR). Tissue microarray (TMA) analysis of samples from 179 cases of OSCC and 10 normal samples oral mucosa were evaluated immunomorphologically. We analyzed CD9 and CD82 expression by qRT-PCR in 66 OSCC cases and 4 normal samples of oral mucosa. Expression of CD63, CD37 and CD81 was not detected in the samples studied. CD82 was downregulated or negative in 127 of 179 (80%) specimens; no correlation was observed between CD82 expression, clinicopathological parameters, disease-free survival and 5-year overall survival. CD9 expression was downregulated or negative in 75 of 129 (42%) OSCC samples. Loss of CD9 expression in OSCC samples correlated with the incidence of lymph node metastasis (p=0.017). Disease-free survival and the 5-year overall survival of patients with downregulated or negative CD9 expression were significantly lower than in patients with positive CD9 expression (p=0.010 and p=0.071, respectively). No correlation was found between CD9 or CD82 expression and clinicopathological parameters by qRT-PCR. Our results suggest that the downregulation or lack of expression of the CD9 protein might indicate a more aggressive of OSCC.
authors.affiliation: Department of Anatomical Pathology, Hospital A.C. Camargo, São Paulo, Brazil. mebuim@hotmail.com
authors.forename: Marcilei Eliza Cavicchioli
authors.initials: ME
authors.lastname: Buim
authors.forename: Silvia Vanessa
authors.initials: SV
authors.lastname: Lourenço
authors.forename: Kátia Candido
authors.initials: KC
authors.lastname: Carvalho
authors.forename: Roberta
authors.initials: R
authors.lastname: Cardim
authors.forename: Cláudia
authors.initials: C
authors.lastname: Pereira
authors.forename: André Lopes
authors.initials: AL
authors.lastname: Carvalho
authors.forename: José Humberto
authors.initials: JH
authors.lastname: Fregnani
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary*; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051861:Kangai-1 Protein / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D060149:Tetraspanin 30; D059470:Tetraspanins; D046888:Tissue Array Analysis
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C059071:CD37 protein, human; C554586:CD63 protein, human; C554798:CD81 protein, human; C497688:CD82 protein, human; C554869:CD9 protein, human; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010980:Platelet Membrane Glycoproteins; C109139:TSPAN4 protein, human; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D060149:Tetraspanin 30; D059470:Tetraspanins