Does JC virus have a role in the etiology and prognosis of Egyptian colorectal carcinoma? REHAB M. SAMAKA, MOSHIRA M. ABD EL-WAHED, HAYAM A. AIAD, MONA A. KANDIL and DALIA R. AL-SHARAKY Pathology Department, Menoufyia University, Shebin El-Kom, Egypt Samaka RM, Abd El-Wahed MM, Aiad HA, Kandil MA, Al-Sharaky DR. JCV in colorectal carcinoma in Egyptian patients. APMIS 2013; 121: 316–28. John Cunningham virus (JCV) encodes an oncogenic T-antigen, which is capable of interacting with key growth regulatory pathways. JCV definite role as causal agent of human cancer, still awaits final confirma- tion. The present study was conducted to assess the possible role of JCV in Egyptian colorectal carcinoma (CRC) and correlate the expression with the clinicopathological features and survival. JCV in situ hybridi- zation (ISH) signals and large T antigen immunoreactivity were examined in 87 colonic specimens. Positive glandular JCV ISH signals were detected in 20%, 25% and 40% of normal, adenoma and CRC cases respectively. Stromal JCV ISH signals were identified in 26% of CRC cases and 5% of adenoma however, normal mucosa did not show stromal positivity with significant difference (p = 0.03). Glandular JCV expression was significantly associated with high grade (p = 0.03), high mitotic index (p=0.02) and low apoptotic index (p = 0.00). Positive stromal signals were significantly associated with low apoptosis (p = 0.00). No positive nuclear immunostaining of JCV large T antigen was detected in all specimens. JCV stromal expression was the 2nd most powerful indicator of short survival and bad prognosis (p = 0.03) in CRC patients. JCV might play an etiological role in CRC tumorogenesis and short survival in Egyptian CRC patients. Key words: John Cunningham virus; in situ hybridization; large T antigen; Colorectal carcinoma. Rehab M. Samaka, Pathology Department, Menoufiya University, Shebin Elkom, Egypt. e-mail: rehabsamaka@yahoo.com Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer in men and the second in women according to recent global health statistics (1). In Egypt, the incidence of CRC according to the National Cancer Insti- tute, Cairo University, is 6.53% (2) and accord- ing to Mokhtar et al., is 2.27% for colon carcinoma and 2.08% for rectal carcinoma (3). An interest in Egyptian CRC has been raised when personal observations and epidemiologi- cal studies revealed a high incidence of the dis- ease among young Egyptian population (4). This uniquely high proportion of early-onset CRC, the early and continuous exposure to hazardous environmental agents and the differ- ent mutational spectrum in Egypt justify fur- ther studies (5). CRC is characterized by aneuploidy and widespread chromosomal rear- rangements that result in the excessive activity of certain growth-stimulating genes and the deletion of other tumor suppressor genes. The mechanism that permits the accumulation of this extreme degree of chromosomal disorders in cancer currently is unexplained (6). There has been gradual acceptance that viruses can participate in the induction of some cancers (7). John Cunningham virus (JCV) is a human polyomavirus that was first isolated from the brain of a patient suffering from progressive multifocal leukoencephalopathy (PML) (8). Recently, a number of reports have detected Received 22 December 2011. Accepted 19 August 2012 316 APMIS 121: 316–328 © 2012 The Authors APMIS © 2012 APMIS DOI 10.1111/apm.12001