Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0.

A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well-documented (≥5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.

Nuclear hTERT immunohistochemical expression is associated with survival of patients with urothelial bladder cancer.

BACKGROUND: The role of telomere in tumorigenesis is complex. While telomerase activation is suggested to be necessary for tumor growth, it may also help in diminishing genetic instability. The expressions of the telomerase reverse transcriptase/hTERT and the telomerase associated protein-1/hTEP-1 were investigated in relation to clinicopathological parameters and various proliferative and apoptotic biological markers. MATERIALS AND METHODS: The immunohistochemical method ABC/HRP was performed on paraffin sections of 132 patients with urothelial bladder carcinomas to detect the proteins hTERT, hTEP-1, Ki-67, bcl-2, p53 and caspase-3. RESULTS: The hTEP-1 protein was localized in the cytoplasm of cancerous cells (56.6%), while the hTERT protein was detected in the nuclei and the cytoplasm of cancerous cells (57.6% and 45.5%, respectively). hTEP-1 demonstrated an association with lower stage of the disease (p = 0.036), as well as both nuclear and cytoplasmic hTERT (p = 0.018 and p = 0.0001, respectively). Cytoplasmic hTERT showed inverse correlation with the mutant p53 protein (p = 0.047), while both cytoplasmic hTERT and hTEP-1 demonstrated parallel correlation with caspase-3 (p = 0.004 and p = 0.048, respectively). Nuclear hTERT associated with improved overall survival in multivariate analysis (p = 0.007). CONCLUSION: The association of the hTERT protein with low stage urothelial carcinomas and improved patients' survival is in keeping with the idea that the early activation of telomerase may protect against genetic instability and the prevalence of aggressive malignant clones.

Enhanced mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in breast carcinomas is correlated with adverse prognosis.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) has emerged as a multifunctional protein with the contrasting activities of inhibiting tissue-degrading enzymes and promoting cellular growth. In an attempt to elucidate the clinical significance of TIMP-1 in breast cancer, the expression of TIMP-1 mRNA was evaluated in 117 invasive breast carcinomas by mRNA in situ hybridization, in correlation with clinicopathological parameters, immunohistochemical prognostic factors (Ki-67, c-erb-B-2, bcl-2) and clinical outcome. TIMP-1 was detected in stromal cells in areas within the tumours and at the tumour margin. High TIMP-1 mRNA expression in the marginal portion of the tumours was significantly correlated with lymph node metastasis (p<0.05) and c-erbB-2 expression (p<0.05). On the other hand, increased TIMP-1 mRNA expression within the tumours showed a statistically significant correlation with ER detection (p<0.01). Multivariate analysis revealed worse survival for patients with high TIMP-1 mRNA expression in the marginal portion of the tumours; the subgroup of these patients co-expressing high levels of TIMP-1 mRNA within the tumours as well had even worse survival (p=0.042). In conclusion, our data support the multifunctional role of TIMP-1, particularly its growth-promoting activity, on the basis of its significant correlation with lymph node metastasis and adverse prognosis. In addition to the latter property, a probable association of TIMP-1 with tumour cell differentiation is suggested by its topographical correlation with ER detection.