The tumor-suppressor protein p53 is over-expressed in a large fraction of squamous-cell carcinomas of the larynx (LSCCs). p53 overexpression is dependent upon the synthesis of mutated versions of the ...protein and has been associated with the malignant progression of certain tumor types. In order to examine the prognostic value of p53 immunodetection in LSCCs, we performed a retrospective analysis on a selected series of tumors, using the PAb 1801 and CM1 antibodies. No significant difference in the frequency of p53 over-expression was observed between tumors from patients with early relapse (67%) and those who had been disease-free for more than 5 years (84%). The lack of correlation of p53 immunoreactivity with clinical stage and differentiation grade of LSCCs, together with the coordinated expression of p53 in primary tumors and the corresponding lymph-node metastases, indicate that p53 over-expression is probably unrelated to the biological aggressiveness of these tumors. In addition, the detection of p53 immunostaining in pre-invasive areas as well as in preneoplastic lesions suggests that p53 abnormalities probably constitute a very early event in LSCC development.
Comparison of human leukocyte antigen (HLA) frequencies in patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and in patients with HCV-associated non-Hodgkin’s lymphoma ...(NHL) has not been addressed previously. To this aim, we investigated the distribution of HLA class II alleles in two selected groups of HCV-infected patients. Group 1 included 50 patients with HCV-associated NHL; group 2 included 29 patients with HCV-associated HCC. A control group included 144 hospitalized patients without NHL or HCC and who were negative for HCV, hepatitis B virus, and human immunodeficiency virus antibodies. Polymerase chain reaction sequence DRB1 and DQB1 specific-primer methods were used. DRB1*1101/DQB1*0301 haplotype, which mainly favors the spontaneous clearance of HCV infection, was lower in HCC subjects than in controls, whereas HLA-DRB1*1104/DQB1*0301, was higher in NHL patients. These findings suggest different pathogenic pathways in HCC and in NHL development. In patients with HCV-associated HCC, a major protective role of DQB1*0301 allele, rather than DRB1*11, was found, probably because of a better HLA class II-associated virus clearance. By contrast, the same allele as HLA-DRB1*04 showed an increase in HCV-associated NHL. These data suggest that NHL and HCC development may be associated to a different response with respect to chronic HLA class II-restricted antigen presentation (perhaps a switch toward CD4+Th2 response in NHL?) or, alternatively, that these alleles could be in linkage disequilibrium to unrelated gene(s), or are in synergy with other immunomodulatory genes that may confer increased risk for NHL.
Epstein-Barr virus (EBV)-positive Hodgkin's and Reed-Stern-berg (HRS) cells express the virus-encoded latent membrane proteins LMP1 and LMP2 that could serve as rejection targets in Hodgkin's disease ...(HD). To examine whether EBV-triggered reactivities can be detected in the tumor, we have compared cytokine mRNA expression, cell phenotype, and cytotoxic activity in biopsies from 8 EBV-carrying and 6 EBV-HD patients. Neither the pattern of lymphokine production nor the cell phenotype of the in vivo-activated interleukin-2-responding populations provided a clear discrimination between EBV+ and EBV cases. HLA class l-restricted EBV-specific cytotoxicity was shown in interleukin-2-dependent cultures from 3 of 3 EBV tumors, whereas cultures from 6 of 6 EBV+ tumors were either noncytotoxic or exerted LAK-type cytotoxicity. EBV-specific cytotoxic T lymphocyte precursors were present in the blood of 1 patient carrying an EBV+ tumor. The results suggest that a tumor-associated suppression of EBV-specific T-cell responses may play an important role in the pathogenesis of EBV+ HD.
Colorectal cancers with high-frequency microsatellite instability show peculiar clinicopathological features and a favorable clinical outcome. We investigated whether the improved prognosis for these ...cancers is related to the content of activated cytotoxic intraepithelial T lymphocytes. Microsatellite instability and the amount of activated cytotoxic lymphocytes were analyzed according to clinicopathological features, survival, and disease recurrence in 109 right-sided colon carcinomas from 245 consecutive patients with stage II/III colon cancer that underwent radical surgery. High-frequency microsatellite instability was found in 43% of stage II/III proximal colon cancers and was associated with significantly higher numbers of activated cytotoxic lymphocytes. High-frequency microsatellite instability, as well as the content of intratumoral-activated cytotoxic T lymphocytes correlated with improved overall and disease-free survival, particularly in patients with stage III tumors. Multivariate analysis revealed that patients with both features had a risk of death and relapse markedly lower than that associated with microsatellite status or intratumoral cytotoxic lymphocytes separately. The presence of local cytotoxic immune responses is probably the major determinant of the good clinical course of patients with microsatellite unstable colon cancer. Furthermore, high-frequency microsatellite instability coupled with a high content of intratumoral cytotoxic lymphocytes may identify a subset of colon cancer patients with a favorable clinical outcome, particularly in stage III disease.
3 Pathogenesis of ocular adnexal lymphoma Ponzoni, M; Dolcetti, R; Magnino, S ...
European journal of cancer supplements,
2010, Letnik:
8, Številka:
4
Journal Article
The presence and distribution of human herpesvirus 6 (HHV-6) variants was investigated by polymerase chain reaction in samples from healthy donors and biopsies from non-Hodgkin's lymphomas and ...Hodgkin's disease. HHV-6 DNA was present in peripheral blood lymphocytes of 17% of healthy donors, variant B three times more frequently than A. HHV-6 was not present in 35 non-Hodgkin's lymphomas of B cell origin and was in only 1 of 10 non-Hodgkin's lymphomas in AIDS patients. HHV-6 DNA was present in 29% of Hodgkin's disease samples; variant B was more frequent than A. Epstein-Barr virus DNA was detected in 38% of Hodgkin's disease biopsies and did not correlate with HHV-6. Thus, the two HHV-6 variants are differently distributed in the healthy population, and the virus probably has no direct role in the development of B cell non-Hodgkin's lymphoma. The detection of HHV-6 DNA in about one-third of Hodgkin's disease biopsies suggests that HHV-6 might be associated with a subset of this disorder.
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