RB1 gene mutations in retinoblastoma and its clinical correlation

Purpose

To find correlation between the type of mutations observed and the severity of the disease using multiple techniques like polymerase chain reactions (PCR), quantitative multiplex PCR, sequencing and RNA analysis.

Methods

Prospective, observational study. Patients who had been screened for mutations in the RB1 gene were included in the study. Patient details including demographic data; age and sex, laterality, international classification of intraocular retinoblastoma (ICIOR) staging, modality of management, histopathology high risk factors if the eyes were enucleated and metastasis rate were assessed.

Results

Seventy four patients were studied. Fifty three patients had bilateral and 21 unilateral disease. Complete genetic data was analyzed for 74 patients and complete clinical correlation was established for all the 49 patients with mutations. Of the total mutations identified, 11/49 (22.4%) of patients had large deletions, 12/49 (24.5%) had small deletions or insertions, 14/49 (28.6%) had nonsense mutations, 7/49 (14.3%) had splice mutations and 5/49 (10.2%) of patients had missense mutations. Four cases were familial. Group E ICIOR stage at presentation was noted in 40% of patients with large deletions, 33% with small deletions whereas 38.5% with splice mutations and 44.4% of patients with missense mutations presented with Group B ICIOR. Twenty five percentages of eyes with large deletions had high risk features on histopathology and one patient among these developed metastasis.

Conclusion

Current laboratory testing of RB1 mutations may be feasible in determining the severity of the disease and patient counseling. The study provides a starting point for looking at correlations.     

Frequent loss of heterozygosity and altered expression of the candidate tumor suppressor gene ' FAT' in human astrocytic tumors

Background  

We had earlier used the comparison of RAPD (Random Amplification of Polymorphic DNA) DNA fingerprinting profiles of tumor and corresponding normal DNA to identify genetic alterations in primary human glial tumors. This has the advantage that DNA fingerprinting identifies the genetic alterations in a manner not biased for locus.     

Pediatric glioblastomas: a histopathological and molecular genetic study

Glioblastoma multiforme (GBM) occurs rarely in children. Relatively few studies have been performed on molecular properties of pediatric GBMs. Our objective in this study was to evaluate the genetic alterations in pediatric GBM (age < or = 18 years) with special reference to p53, p16, and p27 protein expression, alterations of the epidermal growth factor receptor (EGFR), and deletion of the phosphate and tensin homolog gene (PTEN). Thirty cases of childhood GBMs reported between January 2002 and June 2007 were selected, and slides stained with hematoxylin and eosin were reviewed. Immunohistochemical staining was performed for EGFR, p53, p16, and p27, and tumor proliferation was assessed by calculating the MIB-1 labeling index (LI). Fluorescence in situ hybridization analysis was performed to evaluate for EGFR amplification and PTEN deletion. Histopathological features and MIB-1 LI were similar to adult GBMs. p53 protein expression was observed in 63%. Although EGFR protein overexpression was noted in 23% of cases, corresponding amplification of the EGFR gene was rare (5.5%). Deletion of the PTEN gene was also equally rare (5.5%). One case showed polysomy (chromosomal gains) of chromosomes 7 and 10. Loss of p16 and p27 immunoexpression was observed in 68% and 54% of cases, respectively. In pediatric de novo/primary GBMs, deletion of PTEN and EGFR amplification are rare, while p53 alterations are more frequent compared to primary adult GBMs. Frequency of loss of p16 and p27 immunoexpression is similar to their adult counterparts. This suggests that pediatric malignant gliomas are distinctly different from adult GBMs, highlighting the need for identification of molecular targets that may be adopted for future novel therapeutic strategies.     

Oral misoprostol versus intracervical prostaglandin E2 gel for active management of premature rupture of membranes at term

Objective

To compare the efficacy and safety of oral misoprostol with intracervical prostaglandin E2 (PGE2) gel for the active management of premature rupture of membranes (PROM) at term.

Methods

Women with pregnancies between 37 and 42 weeks presenting with PROM at term and a Bishop score of 5 or less were randomly assigned to receive either a 4-hourly oral dose of 50 µg of misoprostol up to a maximum of 3 doses or 2 applications of intracervical PGE2 gel at a 6-hour interval. Oxytocin was given if labor had not started after 12 hours.

Results

Twenty women in the misoprostol group (n = 31) delivered within 12 hours compared with 5 in the PGE2 group (n = 30) (P < 0.001). The induction-to-delivery interval in the misoprostol group was shorter than in the PGE2 gel group (615 min vs 1070 min; P < 0.001). The mode of delivery was comparable between the 2 groups (P = 0.821). Abnormalities in uterine contractions and neonatal outcomes were also comparable. The requirement for oxytocin was lower and patient satisfaction was better in the misoprostol group.

Conclusion

Oral misoprostol is a safe and efficacious alternative to intracervical PGE2 gel in the active management of PROM at term.     

Metabolic Syndrome: An Occupational Perspective

Objective:

To study the prevalence of Metabolic Syndrome (MS) in an Indian industrial setup and to study disparity in occurrence of MS in a working population based on occupational status.

Materials and Methods:

Cross-sectional study of 651 employees who underwent periodic medical examination. The International Diabetes Federation (IDF) definition of MS and International Standard Classification of Occupations (ISCO)-88 classification of occupations were used.

Results:

The overall crude prevalence of MS was found to be 18.5%. Nineteen percent of the non-manual workers and 18.3% of the manual workers suffered from MS. The single largest occupational category with MS was ISCO-88 group 1, which included the managers and senior officials. However, no difference was found among the manual and non-manual workers in prevalence of MS.     

Clinicopathological and molecular characteristics of pediatric meningiomas

Molecular and clinical characteristics of pediatric meningiomas are poorly defined. Therefore, we analyzed clinical, morphological and molecular profiles of pediatric meningiomas. Forty pediatric meningiomas from January 2002 to June 2015 were studied. 1p36, 14q32 and 22q‐deletion were assessed by fluorescent in situ hybridization and mutations of most relevant exons of AKT, SMO, KLF4, TRAF and pTERT using sequencing. Expression of GAB1, stathmin, progesterone receptor (PR), p53 along with MIB‐1 LI was examined using immunohistochemistry. There were 36 sporadic and four NF2 associated meningiomas. Among sporadic meningiomas, the majority (72.2%) of cases harbored 22q‐deletion. Difference in frequency of combined 1p/14q deletion in Grade‐I versus Grade‐II/III tumors was not significant (13.7% vs 28.5%, P = 0.57). PR immunoreactivity was seen in 65.5% of Grade‐I and 14.2% of Grade‐II/III tumors (P = 0.03). The majority (97.2%) of meningiomas were immunonegative for p53. Stathmin and GAB co‐expression was observed in 58.3% of cases. Notably, AKT, SMO, KLF4, TRAF7 (exon 17) and pTERT mutations were seen in none of the cases analyzed. 1p/14q codeletion was frequent in skull base as compared to non‐skull base meningiomas (23% vs 11.1%, P = 0.37). All NF2 meningiomas harbored 22q‐deletion and showed GAB and stathmin co‐expression while none showed 1p/14q loss. Pediatric meningiomas share certain phenotypic and cytogenetic characteristics with adult counterparts, but GAB and stathmin co‐expression in the majority of cases and non‐significant difference in frequency of 1p/14q co‐deletion between low‐ and high‐grade meningiomas indicate an inherently aggressive nature. Characteristic AKT/SMO, KLF4/TRAF7 and pTERT genetic alterations seen in adults are distinctly absent in pediatric meningiomas.     

Juvenile hyaline fibromatosis and infantile systemic hyalinosis: divergent expressions of the same genetic defect?

We describe here a three year-old girl with classic clinical and histological features of juvenile hyaline fibromatosis. We found a history of similar skin findings in her eldest sister, in whom the disorder took a rapidly progressive and fatal course in the second year of life, suggesting either a very severe form of juvenile hyaline fibromatosis, or the possibility of infantile systemic hyalinosis. The similarities and differences between these two described types of hyalinoses have been reviewed in reference to the present report.     

Spinal teratoma with pulmonary differentiation: a report of rare case and review of literature

The occurrence of intradural spinal teratomas in association with spinal dysraphism is uncommon and even rarer is pulmonary differentiation in a teratoma. We report a case of spinal dysraphism, duplication of lumbosacral spine, split cord malformation (SCM I), and meningomyelocele in an 8-month-old child. Excision of meningomyelocele and detethering of cord was done. Pathologic examination revealed a mature teratoma with pulmonary differentiation. To the best of our knowledge this is the second case of spinal teratoma with pulmonary differentiation.