Immunohistochemical Markers for Prognosis of Oligodendroglial Neoplasms

Despite numerous previous studies, oligodendrogliomas continue to generate considerable controversy in the identification of prognostic factors, including single histopathological patterns, and grade of tumor malignancy. The prognostic significance of various pathological and immunohistochemical factors has been intensively examined but numerous studies have yielded conflicting results. In the present study, biopsy samples of 123 oligodendrogliomas were examined immunohistochemically to evaluate a possible association between expression of various tumor-associated antigens and clinical outcome. Both the progression-free and overall survival times were significantly reduced for high-grade tumors, for Ki-S1 labeling index (LI)>10%, for p27 LI<20% and for p18, p53, and vascular endothelial growth factor (VEGF)-positive tumors. For low-grade tumors survival rates were significantly reduced for p27 LI less than 20%, whereas high-grade oligodendrogliomas with Ki-S1 LI greater than 10%, and with p18 positivity revealed significantly shortened survival times. We found no differences in survival times in patients with or without p14ARF, p21, mdm2, and pRb immunoreactivity. Multivariate analysis revealed that risk of oligodendroglioma progression is associated with high-grade tumors, with Ki-S1 LI>10%, and with p27 LI<20%; whereas risk of death is associated with high-grade tumors, with Ki-S1 LI>10%, and with p18 positivity. CART modeling process identified four final groups of oligodendroglioma patients: (1) thirty-nine patients with low-grade tumors and p27 LI>20%; (2) twenty patients with low-grade tumors and p27 LI<20%; (3) thirty-four patients with high-grade tumors and Ki-S1 LI<10%; and (4) thirty patients with high-grade tumors and Ki-S1 LI >10%. In summary, both the p27 and Ki-S1 scores were found to be the strong predictors of oligodendroglioma outcome together with the WHO tumor grade and they seem to be useful for assessing individual prognosis in routinely processed specimens.     

Tumor necrosis factor-alpha and kidney damage in rheumatoid arthritis

AIM: To investigate clinical significance of tumor necrosis factor-alpha (TNF-alpha) and kidney damage in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: 94 patients (84 women and 10 men, mean age 45.2 +/- 11.9 years and the disease duration 7.5 +/- 6.5 years) with RA and 20 donors were examined. In 37(39.4%) and 57(60.6%) patients radiological stages I-II and III-IV, respectively, were determined. TNF-alpha and C-reactive protein (CRP) were measured by ELISA. RESULTS: Serum levels of TNF-alpha in patients with RA appeared significantly higher than in donors (10.9 +/- 22.1 pg/ml vs 0.6 +/- 2.0 pg/ml, p < 0.001). 33 (35.1%) of 94 patients had TNF-alpha levels above 6.6 pg/ml. High serum levels of TNF-alpha correlated significantly with the presence of nephrotic syndrome (r = 0.22, p = 0.03) caused by secondary amyloidosis. There were no correlations between high levels of TNF-alpha and sex, age, disease duration, stages and clinical activity in patients with RA. Positive correlation was found between high levels of TNF-alpha and ESR (r = 0.30, p = 0.003), CRP (r = 0.37, p = 0.0001). CONCLUSION: Thus, TNF-alpha may be involved in pathogenesis of amyloidosis in RA.     

Immunohistochemical study of apoptosis in the cells of experimental injured spinal cord

We studied the temporal and spatial profile of apoptosis following acute spinal cord (SC) injury in rats and influence of chicken yolk transplantation on the programmed cell death. 18 female rats were subjected to complete SC transsection with removal of three millimeters of the SC at the level of the ninth thoracic vertebra. The gap was filled with denaturated chicken yolk in 9 animals. 9 control rats had no transplantation. Temporal and spatial course of apoptosis was estimated in longitudinal sections of the SC by TUNEL assay technique 4 hours, 3 days, 2 weeks, 40 days and 3 months after the injury. Apoptosis occurred through all posttraumatic period with its peak 40 days after the injury and decreased slowly to the minimal level by the third month. Apoptotic cells appeared near the site of the injury immediately after the trauma along the cord several hours later. Apoptosis involved only glial cells, neurons had no apoptotic signs. Suppression of apoptosis occurred in the yolk transplantation group and was accompanied by greater number of neuronal and glial survivals. Thus, apoptotic glial death after transsection of the SC in rats occurred mainly for the first eight weeks along the whole spinal cord.     

Experience in surgical treatment of patients with focal forms of temporal epilepsy

Fifteen patients with focal lesions of temporal epilepsy were examined before and 6 months to 4 years after surgery. There were low-grade gliomas in 13 cases, muscle tissue heterotopy in 1 case, and medial temporal sclerosis in 1. Epileptogenic lesions were localized in the medial structures of the temporal lobe in 10 cases and in the lateral temporal regions in 5 cases. Comprehensive neurophysiological study, including intraoperative electrocorticography, was used to identify an epileptogenic zone (EZ). EZs were found in the medial structures on the affected side in all patients. Lesionectomies were performed in all cases. It was combined with medial resection in 12 cases (it was done in 10 patients until epileptic activity disappeared). Nine patients stopped having seizures after surgery. One patient had only auras. Improvements were slight in 5 patients. A relationship was found between the surgical outcomes and the site of a lesion and EZ. They authors conclude that complete recovery may occur in cases with medial locations of a lesion and EZ. The outcomes of surgery are much poorer in cases with the lateral sites of an lesion and in those with the medial site of EZ.     

p14ARF protein (FL-132) immunoreactivity in intracranial ependymomas and its prognostic significance: an analysis of 103 cases

Although clinical and histological criteria for ependymoma prognosis are recognized, studies have reported contradictory results. Prognostic significance based on immunohistochemistry of ependymomas has been described in a few studies and a strong prognostic value of p53 aberrant expression has been established. Recently, p53 regulation has found to be dependent on the function of the pl4ARF gene product, which has been shown to be critically involved in human carcinogenesis. In this study we have examined patients with intracranial ependymomas (n=103) for immunoexpression of the novel antibody FL-132 to human pl4ARF protein. We found that: (1) the polyclonal FL-132 antibody seems to be suitable for studying pl4ARF protein status in routinely processed and paraffin-embedded specimens; (2) decreasing pl4ARF protein expression is associated with patterns of ependymoma biological aggressiveness, i.e., increasing tumor grade, elevated growth fraction and p53 protein accumulation; however, there was no any association between p14 and MDM2 immunoexpression in ependymomas; (3) although the biological events underlying pl4ARF inactivation in ependymal neoplasms are still unclear, FL-132 immunohistochemistry appears to be useful for assessing an individual prognosis in these tumors; when the p14 score was considered as "high" versus "low" (cut-off p14 labeling index at 10%), it represented an independent prognostic factor in both univariate and multivariate analyses (hazard ratio -3.56; P=0.0003); and (4) most beneficial information for evaluation of malignant ependymoma outcome should be elicited from simultaneous immunohistochemical investigation of p14 ARF and p53 in tumor specimen.