Presence of JC Polyomavirus in Nonneoplastic Inflamed Colon Mucosa and Primary and Metastatic Colorectal Cancer

Abstract

Background: Despite decades of epidemiologic and histopathologic investigations, the association between JC polyomavirus (JCPyV) infection and colorectal cancer (CRC) remains controversial. Objective: This study tested the presence of JCPyV sequences and determined the viral load in a series of colorectal samples from Iranian patients. In total, 223 formalin-fixed paraffin-embedded samples from patients diagnosed with primary and metastatic CRC as well as with nonneoplastic inflamed colon mucosa were analyzed by quantitative real-time PCR for the presence of JCPyV large tumor antigen (LT-Ag) sequences. Results: JCPyV LT-Ag sequences were detected in 18.6% of the CRC tissues and in 15.5% of the nonneoplastic control group. Viral LT-Ag was quantified in 18/100 primary colon adenocarcinomas, 2/10 metastatic adenocarcinomas, and 1/3 primary adenocarcinomas of the rectum. Two JCPyV-positive metastatic tumors presented a negative test result for JCPyV in the corresponding primary tumor. The median JCPyV LT-Ag copy number was 64 × 10^–2 per cell and 14 × 10^–2 per cell in the CRC cases and the nonneoplastic samples, respectively. There was no statistically significant difference between the two study groups regarding median LT-Ag DNA load (p = 0.059). Among the JCPyV-positive samples, the LT-Ag DNA load was higher in 2 metastatic tumors (from a patient with lung metastasis: 232 × 10^–2 copies per cell; from a patient with liver metastasis: 121 × 10^–2 copies per cell). Conclusions: The detection of JCPyV DNA at low copy numbers (lower than 1 viral copy per cell equivalent) and the absence of viral sequences in the corresponding primary tumors of the JCPyV-positive metastatic samples weaken the hypothesis of an etiological role of JCPyV in primary CRC induction.