Assessment and biological significance of JC polyomavirus in colorectal cancer in Tunisia.

PURPOSE: Several reports have indicated the presence of JC polyomavirus (JCV) in many human tumors, including colorectal cancers (CRCs). The presence of JCV infection in CRC patients has not been investigated in African countries. METHODS: We examined the prevalence and the biological significance of JCV in Tunisian CRC patients. The presence of JCV was assessed by polymerase chain reaction (PCR) in a series of 105 CRCs and 89 paired non-tumor colonic mucosa samples from Tunisian patients. Results were correlated with the clinicopathological features and immunohistochemical expression of ß-catenin, p53, and the proliferation marker Ki-67. RESULTS: JCV DNA was detected in 58.1% (61/105) of CRC and in only 14.6% (13/89) of paired non tumor colonic mucosa samples (p=0.03). The presence of JCV was significantly correlated with tumor differentiation (p=0.03). Moreover, JCV presence was significantly correlated with nuclear accumulation of ß-catenin (p=0.008) and p53 accumulation (p=0.0001). Multivariate logistic regression analysis showed that tumor differentiation, ß-catenin and p53 accumulation were independent parameters significantly associated with the presence of JCV in CRC (p=0.04; p=0.05; p=0.001, respectively). CONCLUSION: We support a role of JCV in colorectal carcinogenesis in Tunisian patients, especially of well differentiated morphology.

Proteomic assessment of markers for malignancy in the mucus of intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas evolve from dysplasia to invasive adenocarcinoma. The aims of this study were to look for candidate protein profiles in IPMN mucus according to histological grade, using a differential proteomic technique, and to highlight protein peaks associated with malignant transformation. METHODS: Forty-three mucus samples obtained from surgically resected IPMN and categorized as benign (low/moderate dysplasia) or malignant (severe dysplasia/invasive adenocarcinoma) in 21 and 22 patients, respectively. A surface-enhanced laser desorption ionization time-of-flight mass spectrometry was used to determine candidate protein expression profiles. Protein peaks that significantly differed between benign/malignant IPMN (area under curve > 0.88; P < 10; high intensity) were identified using adapted software. RESULTS: Among 952 protein peaks, 31 were differentially expressed in benign/malignant IPMN (P < 0.001). Among them, 5 candidate proteins of interest (mass-to-charge ratio [m/z]: 5217, 6326, 6719, 10,453, and 10,849 d) were selected by their high diagnostic accuracy and ability to distinguish between malignant and benign tumors. No correlation was found between peak profiles and duct involvement. CONCLUSIONS: Carcinogenic process in IPMN is associated with changes in mucus proteome with characteristic peaks that could be potential candidate biomarkers of malignancy. ABBREVIATIONS: IPMN - intraductal papillary mucinous neoplasm, EPC - extrapancreatic cancer, MRI - magnetic resonance imaging, ERCP - endoscopic retrograde cholangiopancreatography.

Mucinous cystic tumor of the pancreas: immunohistochemical assessment of "ovarian-type stroma".

The new histopathological classification of exocrine pancreatic tumors by the World Health Organization, now includes "ovarian-type stroma" ("OS") in the definition of mucinous cystic tumor of the pancreas (MCT-P). This study investigated the clinicopathological findings of the MCT-P according to WHO classification and scrutinize the function of "OS" in MCT-P immunohistochemically. Thirty-four cases of MCT-P (28 adenomas, 2 borderline tumors and 4 adenocarcinomas) were examined clinicopathologically. The "OS" of 34 MCTs-P were studied immunohistochemically and compared with the stroma of 10 mucinous cystic tumors of the ovary (MCTs-O), 10 conventional pancreatic carcinomas and 6 normal ovaries. Almost all 34 MCTs-P were located in the body-tail of the pancreas of middle-aged women. Histologically the "OS" cells exhibited luteinization in 11/34 (32.4%). Immunohistochemically, both "OS" cells and the stromal cells in MCT-O showed similar positivity rates; calponin (34/34 and 9/10), h-caldesmon (28/34 and 8/10), alpha-inhibin (29/34 and 9/10), estrogen-receptor (21/34 and 6/10) and progesterone-receptor (28/34 and 9/10, respectively). Some neoplastic epithelial cells of MCT-P were positive for human chorionic gonadotropin (hCG) (21/34, 61.8%). This study indicates the predominance of MCT in the distal pancreas of middle-aged women. Furthermore, the immunohistochemical and histological results demonstrate that the "OS" of MCT-P and the stroma of MCT-O share the same characteristics. The results also suggested that the hCG produced by the neoplastic epithelium probably plays an important role in the luteinization of the stroma of MCT-P. We therefore conclude there is a possibility that MCT-P originates from the left remnant primordial gonadal cells which migrated to the pancreatic anlage during the early development of the fetus.