DNA repair gene excision repair cross complementing-group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors

• Published in: Histopathology Vol. 60; no. 3; pp. 489 - 496
• Main Authors: Lima, Lucianne Maia Costa, de Souza, Ludmilla Regina, da Silva, Thiago Fonseca, Pereira, Camila Santos, Guimarães, André Luiz Sena, de Paula, Alfredo Maurício Batista, de Andrade Carvalho, Heloisa
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-02-2012; Blackwell; Wiley Subscription Services, Inc
• Subjects: adjuvant; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Brazil - epidemiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - secondary; Carcinoma, Squamous Cell - therapy; Combined Modality Therapy; Dermatology; DNA repair; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Endonucleases - genetics; Endonucleases - metabolism; Female; Gene Frequency; Gene Silencing; genetic polymorphism; Genotype; head and neck neoplasms; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; Humans; immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Methylation; Middle Aged; Neoplasm Staging; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymorphism, Restriction Fragment Length; radiotherapy; Retrospective Studies; squamous cell carcinoma; Survival Rate; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Brazil; Immunohistochemistry; head and neck neoplasms; Skin disease; Basal cell carcinoma; Genetic variability; Epidemiology; DNA repair; Repair gene; Association; Head and neck; ENT disease; Head and neck squamous cell carcinoma; Adjuvant; Squamous cell carcinoma; Excision; Genotype; Malignant tumor; Radiotherapy; Protein; Anatomic pathology; Treatment; DNA; Head and neck cancer; Methylation; genetic polymorphism; Cancer; Polymorphism
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2011.04062.x

Lima L M C, de Souza L R, da Silva T F, Pereira C S, Guimarães A L S, de Paula A M B & Carvalho H A 
(2012) Histopathology 60, 489–496
DNA repair gene excision repair cross complementing‐group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors
Aims:  To evaluate the associations of excision repair cross complementing‐group 1 (ERCC1) (DNA repair protein) (G19007A) polymorphism, methylation and immunohistochemical expression with epidemiological and clinicopathological factors and with overall survival in head and neck squamous cell carcinoma (HNSCC) patients.
Methods and results:  The study group comprised 84 patients with HNSCC who underwent surgery and adjuvant radiotherapy without chemotherapy. Bivariate and multivariate analyses were used. The allele A genotype variant was observed in 79.8% of the samples, GG in 20.2%, GA in 28.6% and AA in 51.2%. Individuals aged more than 45 years had a higher prevalence of the allelic A variant and a high (83.3%) immunohistochemical expression of ERCC1 protein [odds ratio (OR) = 4.86, 95% confidence interval (CI): 1.2–19.7, P = 0.027], which was also high in patients with advanced stage (OR=5.04, 95% CI: 1.07–23.7, P = 0.041). Methylated status was found in 51.2% of the samples, and was higher in patients who did not present distant metastasis (OR = 6.67, 95% CI: 1.40–33.33, P = 0.019) and in patients with advanced stage (OR = 5.04, 95% CI: 1.07–23.7, P = 0.041). At 2 and 5 years, overall survival was 55% and 36%, respectively (median = 30 months).
Conclusion:  Our findings may reflect a high rate of DNA repair due to frequent tissue injury during the lifetime of these individuals, and also more advanced disease presentation in this population with worse prognosis.