Dimitris Panoussopoulos

Heat shock protein 70 and HLA-DR molecules tissue expression. Prognostic implications in colorectal cancer.

PURPOSE: The expression of 70,000-Da heat shock protein (HSP 70) and HLA-DR molecules on cancer cells influences immunologic mechanisms that may be of some prognostic significance. The purpose of this study was to examine the relationship among immunohistochemical HSP 70, HLA-DR expression, and clinicopathologic tumor variables, as well as patient survival in a series of 128 colorectal carcinomas. METHOD: A three-step immunoperoxidase staining technique was undertaken for detection of both markers. RESULTS: Of the examined carcinomas 77.3 percent were HSP 70-positive and 74.2 percent were HLA-DR-positive. Increased HSP 70-positive expression correlated significantly with low differentiation (P<0.05), showed a tendency to characterize advanced stages of disease, and was clearly associated with worse overall survival (P<0.05). The highest rate of HLA-DR positivity was demonstrated in early stages and was significantly associated with more favorable prognosis (P<0.001). HSP 70-positive/HLA-DR-negative patients had worse overall survival compared with the rest (P<0.001). CONCLUSIONS: The resulting opposite effects on prognosis of examined markers seem to be related to different pathophysiologic functional roles on tumor immunology.

Association between mutations in the CARD15/NOD2 gene and colorectal cancer in a Greek population

Epidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD) is a typical example since patients with longstanding IBD are at increased risk for development of colorectal cancer (CRC). Therefore, genetic factors predisposing to or implicated in the chronic inflammatory process in IBD may simultaneously predispose to CRC. Recently CARD15/NOD2 has been associated with IBD, which further strengthens the notion that the inflammatory response plays a crucial role in this disease. Several mutations have been identified in the CARD15/NOD2 gene, which appear with significantly higher frequency in patients with IBD. In this report, we have examined the frequency of the 3 major mutations R702W, G908R and 3020insC of the CARD2/NOD2 gene in a series of 104 consecutive Greek patients with sporadic colorectal cancer and 100 healthy individuals. The frequency of all the mutations was significantly elevated compared to the control population (R702W, OR=5.00, p=0.023; G908R, OR=2.78, p=0.025; 3020insC, OR=2.44, p=0.017). Patients with advanced stage tumors were more frequently carriers of at least 1 variant in the CARD15/NOD2 gene (p=0.009). Our results suggest that CARD2/NOD2 may be a genetic factor that predispose to sporadic colorectal cancer.

Assessment of JC polyoma virus in colon neoplasms.

PURPOSEResearch data have recently emphasized an intriguing association of JC polyoma virus with colon carcinogenesis. Tumorigenicity of JC virus is attributed to the T-antigen of its Mad-1 variant. Controversy arose when another research group did not confirm this association. The purpose of this study was to detect JC virus in a series of colon neoplasms from Greek patients.METHODSA nested polymerase chain reaction assay was used to detect JC virus in 80 cancerous, 25 adenomatous specimens of large bowel, and 20 colonoscopic biopsy samples from normal patients without colorectal neoplasia. Quantitation of JC virus DNA was performed by real-time polymerase chain reaction.RESULTSJC polyoma virus nucleotide sequence was detected in 61 percent of colon adenocarcinomas and in 60 percent of adenomas, at a viral load of 9 × 103 to 20 × 103 copies/µg DNA. Adjacent normal mucosa in 35 positive colon adenocarcinoma specimens, and normal mucosa from six patients of the control group, had low viral loads (50–450 copies/µg DNA).CONCLUSIONSJC polyoma virus genome is present in colon neoplasms. JC virus detection in adenomas at comparable viral loads to malignant tumors suggests its implication at early steps of colonic carcinogenesis. Taking into consideration other published data, infection of colonic epithelium with JC virus might be a prime candidate for a role in chromosomal and genomic instability.

Evaluation of Cathepsin D immunostaining in colorectal adenocarcinoma

Cathepsin D (CD), an estrogen‐regulated lysosomal protease, has been detected in a variety of tissues. CD expression has been correlated with the invasive potential of breast cancer, acting as an autocrine mitogen or as a protease that degrades the extracellular matrix. The role of CD expression in predicting prognosis or invasive potential in colorectal carcinomas is mostly unknown.

Focal Divergent Chondrosarcomatous Differentiation in a Primary Pleomorphic Liposarcoma and Expression of Transforming Growth Factor 3 Report of a Case and Review of the Literature

A rare case of primary pleomorphic liposarcoma of the thigh with a myxoid component, in which divergent differentiation to a well-differentiated chondrosarcoma was focally present, is described. Presence of heterologous elements has mainly been recognized in the context of dedifferentiated liposarcomas. Few cases of benign mesenchymal tissue have also been reported in well-differentiated and myxoid liposarcomas, while divergent sarcomatous differentiation in liposarcomas appears to be also rare in the absence of dedifferentiation. Positive immunostaining of transforming growth factor-n, which seems to play a role in the formation of bone and cartilage, was demonstrated in our case. Review of the existing literature on the subject has been carried out.