HLA-A*02-B*46 Haplotype: an Adverse Prognostic Factor in Han Patients with Nasopharyngeal Carcinoma

Epidemiological studies have shown that human leukocyte antigen（HLA） allelic polymorphisms are closely correlated to susceptibility to nasopharyngeal carcinoma（NPC）, and in a previous study, we showed that HLA-B＊46 and HLA-A＊02-B＊46 haplotypes were strongly associated with NPC susceptibility. In this retrospective study, we investigated the phenotype of the HLA-A and HLA-B alleles and haplotypes and correlated these data to the clinical and pathological parameters of NPC to understand the role of HLA alleles and haplotypes in NPC prognosis. The cohort comprised 117 NPC patients from a Han population in Xinjiang. The local recurrence-free survival（LRFS）, distant metastasis-free survival（DMFS）, disease-free survival（DFS）, and overall survival（OS） were analyzed. The 5-year DMFS of the HLA-A＊02-B＊46 haplotype carriers and non-carriers was 66.4% and 90.3%, respectively. In addition, age was found to be a prognostic factor for LRFS, DFS, and OS（P=0.032, 0.040, and 0.013, respectively）. We found that the HLA-A＊02-B＊46 haplotype might be a prognostic marker in addition to the traditional TNM staging in patients with NPC.

Relations of proliferative activities of gastric carcinoma cells to lymphatic involvement, venous invasion and prognosis

Background This study was to evaluate bivariate bromodeoxyuridine(BrdUrd)/DNA flow cytometric analysis in detection of gastric carcinoma and to study the relations of cellular BrdUrd labeling indices (LI), G_2/M-phase fraction(G_2/MPF) and DNA ploidy pattern to lymphatic involvement, venous invasion and prognosis.Methods Fresh tumor samples from 60 patients with gastric carcinoma were analyzed by bivariate BrdUrd/DNA flow cytometry. The results were correlated with lymphatic vessel invasion, lymphatic node metastasis, the number of matastatic lymphatic nodes, and venous invasion. Propidium iodide (PI) was used as a fluorescent probe for total cellular DNA, and a monoclonal antibody against BrdUrd was used as a probe for BrdUrd incorporated into DNA. Fluorescent-labeled goat anti-mouse antibody was used as a second antibody. S-phase fractions were measured by in vitro BrdUrd labeling, and DNA ploidy and G_2/MPF were also measured. Comparison of survival was performed with the log-rank test, the Chi-square test for qualitative data, and Student’s t test for quantu data. Results BrdUrd LI and G_2/MPF values were significantly higher in tumors with lymphatic vessel invasion than in those without invasion respectively (P<0.01); the patients who had tumors with lymphatic vessel invasion showed a significantly poor prognosis (P<0.01). Both BrdUrd LI and G_2/MPF values were significantly higher in tumors with lymphatic node metastasis than in those without metastasis (P<0.01). A statistical significant difference was noted in the 5-year survival rates between the patients with lymph node metastasis and those without metastasis. Compared with diploid carcinoma, the incidence of lymph node metastasis was significantly higher in aneuploid carcinoma (P<0.05), and the patients with aneuploid carcinoma showed a significantly poor prognosis (P<0.05). BrdUrd LI was significantly higher in patients with more than 5 metastatic lymph nodes than those with 1-4 metastatic lymph nodes (P<0.05) and those without metastasis (P<0.01). G_2/MPF values in those patients either with more than 5 metastatic lymph nodes or 1-4 metastatic lymph nodes were higher than those without metastasis (P<0.01 and P<0.05). A statistical significance was seen in the 5-year survival rates among the patients with no metastatic lymph node, 1-4 metastatic nodes and more than 5 metastatic nodes (P<0.01). G_2/MPF values were significantly higher in patients with venous invasion than in those without invasion (P<0.01).Conclusions Positive correlations exist between cellular BrdUrd LI, G_2/MPF with lymphatic involvement and prognosis, and DNA aneuploid with lymphatic involvement and prognosis. The same was true between G_2/MPF value and venous invasion in gastric carcinoma.