Expression of Y-box-binding protein YB-1 allows stratification into long- and short-term survivors of head and neck cancer patients.

BACKGROUND: Histology-based classifications and clinical parameters of head and neck squamous cell carcinoma (HNSCC) are limited in their clinical capacity to provide information on prognosis and treatment choice of HNSCC. The primary aim of this study was to analyse Y-box-binding protein-1 (YB-1) protein expression in different grading groups of HNSCC patients, and to correlate these findings with the disease-specific survival (DSS). METHODS: We investigated the expression and cellular localisation of the oncogenic transcription/translation factor YB-1 by immunohistochemistry on tissue micro arrays in a total of 365 HNSCC specimens and correlated expression data with clinico-pathological parameters including DSS. RESULTS: Compared with control tissue from healthy individuals, a significantly (P<0.01) increased YB-1 protein expression was observed in high-grade HNSCC patients. By univariate survival data analysis, HNSCC patients with elevated YB-1 protein expression had a significantly (P<0.01) decreased DSS. By multivariate Cox regression analysis, high YB-1 expression and nuclear localisation retained its significance as a statistically independent (P<0.002) prognostic marker for DSS. Within grade 2 group of HNSCC patients, a subgroup defined by high nuclear and cytoplasmic YB-1 levels (co-expression pattern) in the cells of the tumour invasion front had a significantly poorer 5-year DSS rate of only 38% compared with overall 55% for grade 2 patients. Vice versa, the DSS rate was markedly increased to 74% for grade 2 cancer patients with low YB-1 protein expression at the same localisation. CONCLUSION: Our findings point to the fact that YB-1 expression in combination with histological classification in a double stratification strategy is superior to classical grading in the prediction of tumour progression in HNSCC.

[Tumor-associated prognostic factors of the plasminogen activator family: determination and clinical value of u-PA, t-PA, PAI-1, and PAI-2]. / Tumorassoziierte Prognosefaktoren der Plasminogenaktivator-Familie. Bestimmung und klinische Wertigkeit von u-PA, t-PA, PAI-1 und PAI-2.

Proteolytic factors belonging t the plasminogen activator family (plasmin, u-PA, t-PA, u-PAR, PAI-1, and PAI-2), which usually are involved in blood clotting and degradation of blood clots, are also present in healthy and diseased tissue of the kidney, lung, liver, gastro-intestinal tract, breast, prostate, ovary, and brain. These factors are engaged in brain development, angiogenesis and vascular invasion, wound healing as well as in placenta development and embryogenesis. Plasminogen activators u-PA and t-PA, their inhibitors PAI-1 and PAI-2, and the u-PA-receptor (u-PAR, CD87) are often elevated in solid malignant tumour tissues compared to their normal counterparts. In breast cancer patients, an elevated tumour tissue extract antigen content of u-PA, PAI-1, and u-PAR is associated with increased tumour aggressiveness and poor prognosis; in contrary, an elevated content of t-PA and PAI-2 indicates a favourable prognosis. For clinical relevant determination of these proteolytic factors in tumour tissue extracts, only enzymo-immunometric tests (ELISA) are recommended. Enzymometric and enzymographic tests are actually conducted only in an experimental, preclinical context.

[Hematologic changes in patients under long-term hemodialysis and hemofiltration treatment with special reference to serum concentrations of folic acid and vitamin B 12]. / Hämatologische Veränderungen bei Patienten mit chronischer Hämodialyse- und Hämofiltrationsbehandlung unter besonderer Berücksichtigung der Folsäure- und Vitamin-B12-Serumkonzentrationen.

The incidence of macrocytic anemia has been investigated in 32 patients on maintenance hemodialysis (mean age 46 years, mean duration of dialysis treatment 27.5 months), in 18 patients with combined hemodialysis (HD) and hemofiltration (HF) treatment (mean age 42 years, mean duration of combined HD and HF treatment 6.3 months) and in 32 patients after renal transplantation (mean age 41 years, mean observation period since successful renal transplantation 55.2 months). Also investigated were serum levels of vitamin B12 (radioassay kit 57Co) and folic acid (radioassay kit 125J). Macrocytosis (MCV greater than 96 fl) was observed in 38% of the patients on maintenance hemodialysis, in 44% of the patients with combined HD and HF treatment, and in 47% of the renal transplant recipients. In the chronically dialysed patients, in contrast to the patients with combined HD and HF treatment, the mean serum folic acid level was significantly lower (p less than 0.005) than that of healthy controls. Serum levels of vitamin B12 were within the normal range in all patients. There were no significant differences in serum levels of folic acid and vitamin B12 between the patients with MCV greater than 96 fl and MCV less than or equal to 96 fl. Nor was there a correlation between the serum levels of folic acid or vitamin B12 and mean corpuscular volume. These results suggest that folic acid deficiency is of minor importance in the complex pathogenesis of anemia in hemodialysed patients.