Detection of Genetic Alterations in Oral Squamous Cell Carcinoma Using Multiplex LigationDependent Probe Amplification (MLPA)

@#Deletions and amplifications of genes often occur during multistep progression from oral precancer, seen as oral epithelial dysplasia (OED) to cancerous stage. These genetic alterations could be used as markers to aid in detection of oral squamous cell carcinomas (OSCC). This study explored the use of multiplex ligation-dependent probe amplification (MLPA) technique in detecting OSCC and OED specific genetic alterations. MLPA was used to detect gains and losses of 106 genes in DNA extracted from frozen tissue samples of 10 OSCC and 10 noncancer patients. Two biopsies of OED were analyzed to explore the alterations in oral potentially malignant disorders. There were significant differences (p<0.001) in the number of alterations in OSCC and dysplasia compared to non-cancer samples respectively. The most frequently altered genes in OSCC were PTP4A3, RECQL4, ATM, and KLK3 (60%). Five genes (MYC, SLA, TNFRSF1A, MESDC1, MIF) were altered in 50% of OSCC samples. These nine genes were specific to OSCC samples (p<0.05). Some genes, including MYB, MET, CASP2, SLA and PTEN occurred in 50% of OED samples. MLPA was able to detect genetic alterations, that are present only in the OSCC samples and showed potential to be used as an adjunctive tool in early diagnosis of OSCC.

Beginning of a New Era for the Annals of Dentistry University of Malaya (Ann Dent UM)

@#Since 1994 Ann Dent UM is publishing scholarly contributions in the broader field of Dentistry. Likewise the faculty of Dentistry at Universiti Malay, as the pioneer school of Dentistry in Malaysia, it’s official journal has also pioneered the milestone of dental journal publications in the country. Over the years, the journey for the journal has not always been as smooth as it could have been. Nevertheless 25 years have been a long time to be in existence in the world of scientific peer-reviewed publications.

Diagnostic cerebral angiography in spontaneous intracranial haemorrhage: a guide for developing countries.

OBJECTIVE: Spontaneous intracranial haemorrhage constitutes 18-40% of all stroke cases. Indications for cerebral angiography to find underlying potentially treatable vascular abnormalities are not clear. This study determined which intracranial haemorrhage patients need cerebral angiography by correlating computed tomography (CT) findings, age and hypertension history with cerebral angiography findings. METHODS: A total of 54 patients (8-79 years) with intracranial haemorrhage who underwent both CT examination and six-vessel cerebral angiography were studied over a 2-year period. Cerebral angiography was repeated within 6 weeks if the first angiogram was negative. RESULTS: Angiography detected vascular lesions in 50% of cases (aneurysm 38.9% and arteriovenous malformation, AVM, 11.1%). In the aneurysm group, angiographic yield was 34.3% whereas in the AVM group, it was 37.9%. Subarachnoid haemorrhage (SAH) combined with other types of haemorrhage (such as intracerebral haemorrhage, ICH) was not significantly correlated with the likelihood of finding a vascular lesion, both aneurysm and AVM (p = 0.157). Age less than 50 years had significant correlation (p = 0.021) in the AVM group as well as in the aneurysm group (p < 0.001). A history of hypertension was associated with both aneurysm (p = 0.039) and AVM (p = 0.008). No patients with deep intracerebral haematoma had vascular lesions. The presence of an intravascular haemorrhage (IVH) had significant correlation with aneurysm (p = 0.008) but not AVM. There was no significant difference in mean age between patients with and without a vascular lesion (p = 0.134). CONCLUSION: Cerebral angiography is justified in patients with ICH accompanied by pure SAH (p = 0.001). Other factors associated with finding a vascular lesion were a history of hypertension and the presence of IVH. Diagnostic cerebral angiography is indicated for patients with ICH and SAH and IVH with a history of hypertension, regardless of age.

Absence of Ras, c-myc and Epidermal Growth Factor Receptor (EGFR) Mutations in Human Gliomas and its Clinical Factors Associated with Pathological Grading After Six Years of Diagnosis in North East Malaysian Patients.

Neoplastic transformation appears to be a multi-step process in which the normal controls of cell proliferation and cell-cell interaction are lost, thus transforming normal cells into cancer. The tumorigenic process involves the interplay between oncogenes and tumour suppressor genes. In this study, we have selected the ras family, c-myc and epidermal growth factor receptor (EGFR) genes to detect whether their abnormalities are associated with the expression and progression of glioma cases in Malay patients. We have used the polymerase chain reaction-single stranded conformation polymorphism followed by direct sequencing for the study. For the ras gene family, we screened the point mutations in codons 12 and 61 of the H-, K-, and N-ras gene; for EGFR and c-myc, we analyzed only the exon 1 in glioma samples. In mutational screening analyses of the ras family, c-myc and EGFR gene, there was no mobility shift observed in any tumour analyzed. All patterns of single stranded conformation polymorphism (SSCP) band observed in tumour samples were normal compared to those in normal samples. The DNA sequencing results in all high-grade tumours showed that all base sequences were normal. All 48 patients survived after five years of treatment. In simple logistic regression analysis, variables which were found to be significant were hemiplegia (p=0.047) and response radiotherapy (p=0.003). Hemiplegics were 25 times more likely to have high pathological grade compared to those without. Patients with vascular involvement were 5.5 times more likely to have higher pathological grade. However, these findings were not significant in multivariate analysis. Patients who had radiotherapy were nearly 14 times more likely to have higher pathological grade. Multivariate analysis revealed that patients with hemiplegia were more likely to have higher pathological grade (p= 0.008). Those with higher pathological grading were 80 times more likely to have radiotherapy (p=0.004).

Analysis of pediatric subdural empyema outcome in relation to computerized tomography brain scan.

A cross-sectional study was conducted to predict the outcome in patients with subdural empyema, using initial and post-treatment CT scan brain parameters. Data collection was done on those children who were diagnosed to have subdural empyema by CT scan of the brain with contrast, who underwent burrhole evacuation, from February 2000 until April 2002. Numerous factors, such as coma or loss of unconsciousness at diagnosis, age, types of antibiotic, microbiology, extension of empyema, associated cerebral infarction and ventriculitis, were analyzed. Poor prognosis was associated with loss of consciousness, and hypodensity by CT scan at presentation (p < 0.005). Patients with an extensive subdural empyema will have a good outcome if they are treated early and aggressively with antibiotics and burrhole evacuation.

Molecular genetic analysis of anaplastic pleomorphic xanthoastrocytoma.

A case of pleomorphic xanthoastrocytoma in a 10-year-old Malay boy is reported. The patient presented with headache and epilepsy. On computed tomography, a ring-enhancing low-density lesion was observed in the left fronto-temporal area. During surgery, a cystic tumour containing serous fluid was found and almost totally removed. Histologically, the tumour exhibited marked pleomorphism of oval and spindle-shaped cells intermixed with uni- and multinucleated giant cells, and xanthomatous cells with foamy cytoplasm. The tumour displayed pericellular reticulin and periodic acid-Schiff positive granules. Focally, six mitotic characters per 10 high-power fields were seen, and necrosis was confined only to the inner lining of the cyst. Mutational analysis showed that a frameshift mutation (a 4-bp deletion) in the p53 gene had occurred in codons 273 and 274 of exon 8. No mutation was detected in the p16 gene. No allelic loss and/or loss of heterozygosity were observed on chromosome 10 using microsatellite marker D105532. The patient was treated with postoperative radiotherapy because of histological anaplasia and the presence of residual tumour. The patient showed marked neurological recovery after a follow-up period of 2 years.

Intramedullary spindle cell hemangioendothelioma of the thoracic spinal cord--case report.

A 28-year-old Malay man presented with progressive paraparesis over a period of 6 months. Magnetic resonance imaging of the spine revealed a thoracic intramedullary spinal cord tumor at the T-7 level with homogeneous enhancement following intravenous gadolinium administration. Laminectomy and partial decompression of the tumor was performed. Histological examination of the tumor revealed features of spindle cell hemangioendothelioma. The patient was managed with limited field radiotherapy followed by systemic interferon therapy. Good neurological improvement was seen subsequently. The patient has survived 48 months with growth restraint at the primary site, although residual neurological deficit persists. Immunotherapy should be considered as a treatment modality for intramedullary hemangioendothelioma of the spinal cord after surgery and radiotherapy.