Immunohistochemical expression of histone modification pattern in adult glioblastoma.

BACKGROUND: Despite the growing advances in molecular research and therapeutics, glioblastomas are still considered highly invasive aggressive tumors with a median survival of 15 months. Genetic alterations have been studied in detail; however, additionally, there is now growing evidence on the role of epigenetic alterations in glioblastoma. Recently, histone modification patterns have been found to have a significant part in gene expression and prognosis. However, further research in this field is warranted to establish its role for the betterment of these patients with the deadly disease. AIMS: To determine the immunohistochemical expression of histone modifications like histone-3-lysine-18 acetylation (H3K18Ac) and histone-4-lysine 20 trimethylation (H4K20triMe) in glioblastoma patients. MATERIALS AND METHODS: This is a retrospective study of 48 glioblastoma patients who underwent surgery. Immunohistochemistry (IHC) for tri-methyl-histone-H4 (Lys20) (H4K20triMe) and acetyl-histone-H3 (Lys18) (H3K18Ac) was performed in paraffin-embedded tissues manually, and the expression was noted. Data on the mitotic index and overall survival was collected and statistically analyzed. RESULTS: The mean age was 50 years with a M: F ratio of 1.6:1. Out of 48 cases, 60% (28 cases) demonstrated positivity for H3K18Ac and 98% (46 cases) for H4K20triMe. The pattern of expression was nuclear with increased expression adjacent to necrosis and at the invasive front. The overall median Q score for H3K18Ac was 1/12 and for H4K20triMe was 6/12. No significant statistical significance was observed between histone expression, Ki67%, and overall survival. CONCLUSION: Histone modification patterns are being explored in detail in an array of tumors. They also have a potential role in glioblastoma for risk stratification and instituting appropriate treatment based on the prognosis. Epigenetic changes like histone modification patterns, in addition to genetics, can pave the way for a better molecular understanding of glioblastomas and provide hope in the future to improve the survival of these patients with deadly diseases.

Radiation-Induced Papillary Meningioma: A Case Report.

Meningiomas are the most common tumors that develop following cranial radiotherapy. They have a shorter latency period and an aggressive behavior when compared with spontaneously occurring meningiomas. We report a 69-year-old male who underwent high-dose radiotherapy for recurrent pituitary adenoma and later developed temporal high-grade meningioma which was excised. Patient developed tumor bed bleed twice in the postoperative period and succumbed subsequently to the disease. After a thorough review of literature, this may be the second case of radiation-induced grade III papillary meningioma which has been reported.

Isolated ruptured dissecting aneurysm of PICA with extremely narrow neck managed by a novel endovascular technique-a case report and review of literature.

Dissecting aneurysms of posterior inferior cerebellar artery (PICA) are usually extensions of vertebral artery dissection. Isolated dissecting aneurysms of PICA are extremely rare. A 5-month-old female child presented with history of fall from a height of around 2 ft., followed by incessant crying and multiple episodes of vomiting. The anterior fontanelle was lax. Plain CT scan brain showed IVH in the fourth ventricle with no hydrocephalus. Twenty-four hours after admission, the child had one episode of vomiting and became unresponsive. The child was intubated, and a repeat CT scan brain showed thick acute SDH in the posterior fossa with hydrocephalus. Emergency suboccipital craniectomy and evacuation of thick acute subdural hematoma were done. Organized clot noted in the midline between the tonsils was not removed. Digital subtraction angiography (DSA) done 48 h after surgery showed ruptured dissecting aneurysm of left PICA. Endovascular temporary parent artery occlusion by coil deployment was performed, after which a check angiogram revealed complete exclusion of aneurysm from circulation. Endovascular proximal parent artery occlusion is the preferred treatment modality for dissecting aneurysms of PICA. Selective coil or Onyx embolization of the aneurysm with parent vessel preservation technique is a valid and increasingly used alternative. In this case, a novel technique of endovascular temporary parent artery occlusion by coil deployment was performed successfully. This technique may be recommended in select cases.

A Rare Case of a High-Grade Astroblastoma with 5-Year Follow-up.

Astroblastoma is a very rare glial tumor derived from astroblasts. It has been controversial in terms of its features and diagnosis. The objective of this report is to present the findings of the high-grade astroblastoma with a good prognosis in a 21-year-old female who presented to us with diplopia and headache. While imaging led to the foremost differentials of pleomorphic xanthoastrocytoma and Ganglioglioma which are low-grade neoplasms, the final diagnosis was established on microscopy and immunohistochemistry after excision. Treatment protocol included surgery with postoperative radiotherapy and chemotherapy. Due to controversial and limited literature, this tumor poses difficulties in diagnosis and management. This is a rare, successfully managed case of astroblastoma with a positive outcome 5 years after the diagnosis was established. In this case report, we review the steps of diagnosis, the differentials, the pathological and histological features, and the management of this rare entity.

Clinical Evaluation of Proline, Glutamic acid, and Leucine-Rich Protein 1 Expression in Astrocytomas and Correlations with the Proliferation Marker Ki-67.

Malignant astrocytomas presenting in humans of any age group are a challenge to diagnose and treat. Hence, there is a quest for new markers to ascertain their grades and predict disease outcomes. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a nuclear receptor co-regulator, is an oncogene found in various cancers. We postulate that by screening for PELP1, its correlation with survival outcomes of patients across various grades can indicate a plausible novel diagnostic marker and a potential therapeutic target in gliomas. Immunostaining of 100 cases of astrocytomas for PELP1 was performed on paraffin-embedded sections. Results showed that PELP1 expression increases with higher grades; the mean H-score of PELP1 in grade-I astrocytomas was determined to be 112.3, whereas in grade-IV it was 235.1 (P value = 0.0001). Survival analysis of patients with H-score of 200-300 was only 8.8% and 68.8% in patients with scores of 0-100. PELP1 expression in high-grade astrocytomas is an important factor in determining the outcomes. Graphical abstract Evaluation of molecular expression of PELP1 along with Ki-67 LI signifies a linear increase in its expression pattern among different grades of astrocytomas from low- to high-grade tumors, which can serve as a potential prognostic molecular marker in differentiating various types of astrocytomas in humans.

Clinical Evaluation of P21 Activated Kinase 1 (PAK1) Activation in Gliomas and Its Effect on Cell Proliferation.

Glioblastomas are the primary malignant tumors of brain tissues with poor prognosis and highly invasive phenotypes. Till now Ki-67 LI has emerged as a well-studied proliferation marker that aids in tumor grading, but labeling index alone cannot predict overall survival in gliomas. P21 activated kinase 1 (PAK1) - a serine/threonine kinase has been shown to function as downstream nodule for various oncogenic signaling pathways that promote neoplastic changes. This study is designed to evaluate the expression of PAK1 across various grades and its correlation with Ki-67 LI and overall survival rates among a total number of 140 clinical brain tumors of glioma patients. We also studied the activation status of phospho PAK1 in glioma tissues and established the role of PAK1 in proliferation of glioblatoma cell lines under γ-irradiation.This study provides molecular evidence signifying the role of PAK1 and its activation status in the progression of Gliomas to more aggressive phenotypes.