Immunohistochemical characteristics of bladder cancer in patients with virus-positive tumors

Abstract

Background. Viral infection is a major factor in virus-associated carcinogenesis.Objective: to evaluate the expression of growth factors and markers of apoptosis, proliferative activity, and angiogenesis in patients with viral DNA-positive bladder cancer.Materials and methods. The study included 100 bladder cancer patients (72 males and 28 females) aged between 38 and 90 years (mean age 65 ± 10). Tumor tissue samples were tested by polymerase chain reaction to detect DNA of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2 respectively), high-risk human papillomavirus (HPV), cytomegalovirus (CMV), and Epstein—Barr virus (EBV). Immunohistochemical analysis was performed in 32 patients and included the following markers: proliferation marker Ki-67, p63, apoptosis regulator Bcl-2, p53, angiogenesis marker CD31, adhesion protein CD44, and epidermal growth factor receptor (EGFR).Results. Viral DNA in tumor tissue was detected in 34 patients; of them, 50 % had poorly-differentiated tumors. Twenty-seven patients were found to have EBV DNA in their tumor tissue; 6 patients had CMV DNA; 5 patients had high-risk HPV DNA (types 16, 39, 45, 52, and 59); 1 patient had HSV1 and HSV2 DNA. Four out of 34 participants had mixed infections (1 case of HPV 59 + EBV; 2 cases of EBV + CMV; 1 case of CMV + EBV + HPV 31 and 52). We observed a strong correlation between the presence of EBV DNA and levels of CD31 and Ki-67 expression as well as between high-risk HPV DNA and Bcl-2 expression. High levels of antibodies against EBV capsid antigen were associated with EGFR and Ki-67 expression, whereas the level of antibodies against EBV nuclear antigen correlated with CD44 expression. We evaluated specific characteristics of expression of the markers analyzed depending on the tumor stage, grade of anaplasia, and recurrence. We also assessed morphological characteristics of changes in lymphocytic and plasma cell infiltrates.Conclusion. We found a correlation between the presence of viral DNA in bladder cancer tissue and markers of proliferative activity, angiogenesis, and apoptosis. Viral infection is likely to increase proliferative activity and suppression of apoptosis, which may cause tumor progression. Further studies are needed to assess this correlation.