TY - CHAP
T1 - Tetraspanins CD9 and CD151, epidermal growth factor receptor and cyclooxygenase-2 expression predict malignant progression in oral epithelial dysplasia.
AU - Nankivell, P
AU - Williams, H
AU - McConkey, C
AU - Webster, K
AU - High, A
AU - MacLennan, K
AU - Senguven, B
AU - Rabbitts, P
AU - Mehanna, H
PY - 2013/11/26
Y1 - 2013/11/26
N2 - BACKGROUND: Prognostic biomarkers aim to improve on the current inadequate method of histological assessment to identify patients with oral epithelial dysplasia at greatest risk of malignant transformation. We aimed to assess the prognostic ability of six protein biomarkers linked to the epidermal growth factor receptor (EGFR) pathway, including three tetraspanins, in a large multicentre oral dysplasia cohort. METHODS: One hundred and forty-eight cases with varying degrees of epithelial dysplasia underwent immunohistochemical assessment for CD9, CD151, CD82, EGFR, Her-2, and COX-2. Scoring was performed independently by two observers. Univariate analyses using both logistic and Cox regression models and a multivariate regression were performed. RESULTS: Malignant progression was significantly greater in those cases with decreased expression of CD9 (P=0.02), and increased expression of CD151 (P=0.02), EGFR (P=0.04), and COX-2 (P=0.003). Histological grade (P=0.0002) and morphology (P=0.03) were also prognostic, whereas smoking and alcohol were not. The optimal combination by backward-variable selection was of histological grade (hazard ratio (HR) 1.64; 95% CI 1.12, 2.40), COX-2 overexpression (HR 1.12; 1.02, 1.24) and CD9 underexpression (HR 0.88; 0.80, 0.97). CD82 and Her-2 demonstrated no prognostic ability. CONCLUSION: This is the first study of the expression and prognostic potential of the tetraspanins in oral dysplasia. A combination of certain biomarkers with clinical factors appeared to improve the accuracy of determining the risk of malignancy in individuals with oral dysplasia. These findings may also offer potential new therapeutic approaches for this condition.
AB - BACKGROUND: Prognostic biomarkers aim to improve on the current inadequate method of histological assessment to identify patients with oral epithelial dysplasia at greatest risk of malignant transformation. We aimed to assess the prognostic ability of six protein biomarkers linked to the epidermal growth factor receptor (EGFR) pathway, including three tetraspanins, in a large multicentre oral dysplasia cohort. METHODS: One hundred and forty-eight cases with varying degrees of epithelial dysplasia underwent immunohistochemical assessment for CD9, CD151, CD82, EGFR, Her-2, and COX-2. Scoring was performed independently by two observers. Univariate analyses using both logistic and Cox regression models and a multivariate regression were performed. RESULTS: Malignant progression was significantly greater in those cases with decreased expression of CD9 (P=0.02), and increased expression of CD151 (P=0.02), EGFR (P=0.04), and COX-2 (P=0.003). Histological grade (P=0.0002) and morphology (P=0.03) were also prognostic, whereas smoking and alcohol were not. The optimal combination by backward-variable selection was of histological grade (hazard ratio (HR) 1.64; 95% CI 1.12, 2.40), COX-2 overexpression (HR 1.12; 1.02, 1.24) and CD9 underexpression (HR 0.88; 0.80, 0.97). CD82 and Her-2 demonstrated no prognostic ability. CONCLUSION: This is the first study of the expression and prognostic potential of the tetraspanins in oral dysplasia. A combination of certain biomarkers with clinical factors appeared to improve the accuracy of determining the risk of malignancy in individuals with oral dysplasia. These findings may also offer potential new therapeutic approaches for this condition.
KW - 80 and over
KW - Adult
KW - Aged
KW - Antigens
KW - Biological
KW - Biological: metabolism
KW - CD151
KW - CD151: metabolism
KW - CD9
KW - CD9: metabolism
KW - Cell Transformation
KW - Cohort Studies
KW - Cyclooxygenase 2
KW - Cyclooxygenase 2: metabolism
KW - Epidermal Growth Factor
KW - Epidermal Growth Factor: metabolism
KW - Female
KW - Glandular and Epithelial
KW - Glandular and Epithelial: diagnosis
KW - Glandular and Epithelial: metabolism
KW - Humans
KW - Male
KW - Middle Aged
KW - Mouth Neoplasms
KW - Mouth Neoplasms: diagnosis
KW - Mouth Neoplasms: metabolism
KW - Neoplasms
KW - Neoplastic
KW - Neoplastic: metabolism
KW - Precancerous Conditions
KW - Precancerous Conditions: diagnosis
KW - Precancerous Conditions: metabolism
KW - Precancerous Conditions: pathology
KW - Prognosis
KW - Receptor
KW - Retrospective Studies
KW - Tumor Markers
KW - Young Adult
U2 - 10.1038/bjc.2013.600
DO - 10.1038/bjc.2013.600
M3 - Chapter
C2 - 24201754
SN - 1532-1827 (Electronic)\r0007-0920 (Linking)
T3 - British journal of cancer
SP - 2864
EP - 2874
BT - British journal of cancer
ER -