Epigenetic patterns on the level of DNA methylation have already been shown to separate clinically relevant subgroups of meningiomas. We here set out to identify potential prognostic implications of epigenetic modification on the level of histones with focus on H3K27 trimethylation (H3K27me3). H3K27me3 was assessed by immunohistochemistry on 232 meningiomas from 232 patients. In 194 cases, trimethylation was detected in tumor cells. In 25 cases, staining was limited to vessels while all tumor cells were negative. Finally, 13 cases yielded equivocal staining patterns. Reduced abundance of H3K27me3 in cases with staining limited to vessels was confirmed by mass spectrometry on a subset of cases. Lack of staining for H3K27me3 in all tumor cells was significantly associated with more rapid progression (p = 0.009). In line, H3K27me3-negative cases were associated with a DNA methylation pattern of the more aggressive types among the recently introduced DNA methylation groups. Also, NF2 and SUFU mutations were enriched among cases with complete lack of H3K27me3 staining in tumor cells (p < 0.0001 and p = 0.029, respectively). H3K27me3 staining pattern added significant prognostic insight into WHO grade II cases and in the compound subset of WHO grade I and II cases (p = 0.04 and p = 0.007, respectively). However, it did not further stratify within WHO grade III cases. Collectively, these data indicate that epigenetic modifications beyond DNA methylation are involved in the aggressiveness of meningioma. It also suggests that H3K27me3 immunohistochemistry might be a useful adjunct in meningioma diagnostics, particularly for cases with WHO grade II histology or at the borderline between WHO grade I and II.
Background:Prostate cancer is a major health problem throughout the developed world. Tumor grade is one of the most important prognostic factors of prostate cancer. At present, adequate prognostic markers for prostate cancer progression are still lacking, in spite of intensive investigation. Accordingly, we studied the role of immunohistochemical (IHC) expression of p53 and Ki-67 as a prognostic factor in carcinoma prostate and correlated their expression with Gleason's grade.Materials and Methods:In this prospective study, a total of 60 cases including 50 cases of prostate carcinoma and 10 of benign prostatic hyperplasia (BPH) were taken. Tumor grade was determined according to Gleason's grading system. p53 and Ki-67 expressions were determined by IHC staining. The obtained results were analyzed and evaluated using Spearman's statistical test (SPSS version 20).Results:In BPH, p53 was expressed in only 2 of 10 (20%) cases while in carcinoma it was expressed in 38 of 50 (76%) cases. Ki-67 was expressed in only 1 of 10 (10%) BPH cases while in carcinoma it was expressed in 32 of 50 (64%) cases. In present study, 1 of 4 (25%) well differentiated, 23 of 31 (74.19%) moderately differentiated and 14 of 15 (93.33%) poorly differentiated tumors revealed p53 immunopositivity and a statistically significant correlation was observed between p53 expression and increased Gleason's grade (P = 0.038). All 4 (100%) cases of well-differentiated carcinoma were negative for Ki-67 expression. Nineteen of 31 (61.29%) moderately differentiated and 13 of 15 (86.66%) poorly differentiated tumors were positive for Ki-67 and a statistically significant correlation was observed between Ki-67 positivity and increased Gleason's grade (P = 0.002).Conclusions:Both p53 and Ki-67 were significantly up-regulated in malignant lesions as compared to benign lesions and a strong relationship with the Gleason's grading was noticed, therefore, we propose that these markers can be applied along with other prostate cancer prognostic factors.
Background:Various histopathological changes have been observed following neoadjuvant chemotherapy in individual tumors in the literature.Aims and Objectives:To observe histopathologic changes seen after neoadjuvant chemotherapy in breast malignancies, squamous cell carcinomas, adenocarcinomas, and Wilms′ tumor using breast cancer predominantly as the model.Materials and Methods:The present prospective study was carried out on 60 patients including 40 patients with carcinoma breast and 20 patients with other malignancies who received neoadjuvant chemotherapy.Results:Post neoadjuvant chemotherapy, mastectomy specimens revealed nuclear enlargement, nuclear shrinkage, necrosis, vacuolation of nucleus, vacuolation of cytoplasm, dyscohesion, and shrinkage of tumor cells with nuclear changes of nonviability like karyorrhexis, karyolysis, and pyknosis. Stromal reactions manifested as fibrosis, elastosis, collagenization, hyalinization, microcalcification, and neovascularization. Areas of necrosis included both vascular and avascular pattern. The stroma also revealed fibrinoid necrosis and mucinous change. Hyalinization of the blood vessel wall was a common finding. The most common inflammatory host response observed in the present study was lymphocytic; others included mixed inflammation, plasmacytic, prominent histiocytic, and giant cell types. Giant cell reaction was significantly correlated to all types of tumor responses (P < 0.05). Similar changes were also observed in other malignancies. A detailed review of the literature has also been done and presented.Conclusion:The tumor grade decreases and differentiation improves, in addition to the retrogressive changes and increase in stromal component, as a result of chemotherapy in carcinoma breast as well as in other malignancies.
OBJECTIVECerebral venous sinus thrombosis (CVST) is a known complication of surgeries near the major dural venous sinuses. While the majority of CVSTs are asymptomatic, severe sinus thromboses can have devastating consequences. The objective of this study was to prospectively evaluate the true incidence and risk factors associated with postoperative CVST and comment on management strategies.METHODSA prospective study of 74 patients who underwent a retrosigmoid, translabyrinthine, or suboccipital approach for posterior fossa tumors, or a supratentorial craniotomy for parasagittal/falcine tumors, was performed. All patients underwent pre- and postoperative imaging to evaluate sinus patency. Demographic, clinical, and operative data were collected. Statistical analysis was performed to identify incidence and risk factors.RESULTSTwenty-four (32.4%) of 74 patients had postoperative MR venograms confirming CVST, and all were asymptomatic. No risk factors, including age (p = 0.352), BMI (p = 0.454), sex (p = 0.955), surgical approach (p = 0.909), length of surgery (p = 0.785), fluid balance (p = 0.943), mannitol use (p = 0.136), tumor type (p = 0.46, p = 0.321), or extent of resection (p = 0.253), were statistically correlated with thrombosis. All patients were treated conservatively, with only 1 patient receiving intravenous fluids. There were no instances of venous infarctions, hemorrhages, or neurological deficits. The rate of CSF leakage was significantly higher in the thrombosis group than in the nonthrombosis group (p = 0.01).CONCLUSIONSThis prospective study shows that the radiographic incidence of postoperative CVST is higher than that previously reported in retrospective studies. In the absence of symptoms, these thromboses can be treated conservatively. While no risk factors were identified, there may be an association between postoperative CVST and CSF leak.
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