Abstract 4776: Expression of Human Papillomavirus E6 and E7 genes in colorectal cancer.

Abstract

Abstract Purpose: The role of human papillomavirus (HPV) has been well established in the pathogenesis on cervical cancers and anogenital. However, HPV-DNA has also been detected in tumor tissues of other malignancies such as head and neck cancer, esophageal cancer, and some skin cancers. Viral genes expression and multiplication occur exclusively in the nuclei of the infected cells and are tightly linked to the state of differentiation of the cells. Integration of viral DNA into host genome is essential for carcinogenesis since it promotes disruption of HPV E2 gene, leading to abnormal expression of E6 and E7 oncoproteins. Both E6 and E7 can form specific complexes with tumor suppressor gene p53 and pRB respectively. However, the role of HPV in the pathogenesis of colorectal cancer is still undetermined. Our objectives were (1) to evaluate the presence of HPV infection in patients with CRC; (2) to type HPV positive cases using primer specific for HPV-16, and (3) to determine the mRNA expression levels of the viral oncogenes HPV-16 E6 and HPV-16 E7. Experimental Designs: To determine the association of HPV and CRC, we conducted an age-and-gender matched case-control study using tumor and tumor-adjacent colorectal tissues from patients with CRC (cases) and without CRC (controls). Presence of L1, E2, and E6 genes was analyzed to determine whether a full-length HPV genome existed in tumor and normal tissue samples. Human HPV-16 DNA detection was performed by a nested PCR strategy using the PGMY09/PGMY11 as outer primer, and GP5+/GP6+ as inner primers. We detected the expression of E6 and E7 mRNA in the HPV-16 (+) cases. Hypothesis testing was performed using Pearson Chi-square analysis of proportions and conditional logistic regression using SPSS 17. Results: A total of 54 (ß-actin+) CRC patients (mean age 61 ±11 years, 27 males) and 36 controls (mean age was 60 ± 9 years, 18 males) were evaluated. HPV DNA was identified in 25 of 54 (46.3%) patients with CRC and in 1 of 36 (2.8%) controls (OR = 25.58; 95% CI 3.22 to 203.49, p < 0.001). HPV-16 was identified in 18 of 25 (72.0%) HPV-positive CRC cases, and in one (2.8%) control was HPV (+). All 18 HPV-16 CRC cases showed expressed E6 mRNA. Six of 18 (33.3%) HPV-16 positive cases expressed E7 mRNA. Among the 12 CRC cases where both tumor and adjacent tissue was available, 2 of 9 (16.7%) exhibited HPV-16 DNA in both tumor and tumor-adjacent tissues. Conclusion: These results support that colorectal HPV infection is common among patients with CRC. The high presence of HPV in tumors located proximal to the rectum suggests that this infection might not result from direct spread from anogenital sites. Moreover, our finding of highly frequent active expression of E6 and E7 viral oncogenes in the host strongly suggests that HPV oncoproteins may play a role in the pathogenesis of colorectal carcinogenesis. Citation Format: Wesley Villavicencio-Torres, Mercedes Y. Lacourt-Ventura, Sharon C. Fonseca-Williams, Maria Del Mar Gonzalez- Pons, Yaritza Diaz-Algori, Carlos Torres-Ramos, Raul D. Bernabe-Dones, Marcia R. Cruz-Correa. Expression of Human Papillomavirus E6 and E7 genes in colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4776. doi:10.1158/1538-7445.AM2013-4776