Bishan Dass Radotra

Alterations of tumor suppressor gene p16INK4a in pancreatic ductal carcinoma.

BackgroundCell cycle inhibitor and tumor suppressor gene p16 / MTS-1 has been reported to be altered in a variety of human tumors. The purpose of the study was to evaluate primary pancreatic ductal adenocarcinomas for potentially inactivating p16 alterations.MethodsWe investigated the status of p16 gene by polymerase chain reaction (PCR), nonradioisotopic single strand conformation polymorphism (SSCP), DNA sequencing and hypermethylation analysis in 25 primary resected ductal adenocarcinomas. In addition, we investigated p16 protein expression in these cases by immunohistochemistry (IHC) using a monoclonal antibody clone (MS-887-PO).ResultsOut of the 25 samples analyzed and compared to normal pancreatic control tissues, the overall frequency of p16 alterations was 80% (20/25). Aberrant promoter methylation was the most common mechanism of gene inactivation present in 52% (13/25) cases, followed by coding sequence mutations in 16% (4/25) cases and presumably homozygous deletion in 12% (3/25) cases. These genetic alterations correlated well with p16 protein expression as complete loss of p16 protein was found in 18 of 25 tumors (72%).ConclusionThese findings confirm that loss of p16 function could be involved in pancreatic cancer and may explain at least in part the aggressive behaviour of this tumor type.

HISTOMORPHOLOGY OF RENAL DYSPLASIA—AN AUTOPSY STUDY

A retrospective analysis of pediatric autopsies in the past 18 years was done with the aim of studying the histomorphology of renal dysplasia. Renal dysplasia comprised 150 (3.66%) of the 4,099 pediatric autopsies from 20 weeks of gestation to 1 year of life. Primitive ducts with the fibromuscular collar, the sine qua non of renal dysplasia, was seen in all cases. Lobar disorganization and cysts were seen in all cases except for the 7 cases of hypodysplasia. Other elements were seen in varying proportions: cartilage in 33.7%, bone in 1.08%, thickening of basement membrane of the primitive ducts in 64.13%, extramedullary hematopoiesis in 98.9%, nerve twigs in 72.8%, and nodular renal blastema in 2.17% cases. In unilateral multicystic dysplasia/renal agenesis, the contralateral kidney showed abnormalities in 44.45% and 47.37% of cases, respectively.

Bcl-XL protein levels determine apoptotic index in pancreatic carcinoma.

Objectives: The present study was designed to analyze the expression of the major antiapoptotic molecules Bcl-2, Bcl-XL and the proapoptotic Bax in pancreatic ductal carcinoma and their correlation to the extent of apoptosis. Methods: Tissue samples were obtained from patients (age, 27-78 years) having surgery for pancreatic cancer. Normal pancreatic tissue away from the main tumor mass was also analyzed. The levels of Bcl-2, Bcl-XL, and Bax mRNA expression were analyzed by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). The presence of corresponding proteins was determined by immunohistochemistry (IHC). The apoptotic index was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Results: A total of 25 cases were analyzed. The apoptotic index (percentage) ranged from 0.0% to 1.8%, with a median of 0.26. Semiquantitative RT-PCR revealed variable mRNA expression, with the Bcl-2/Bax ratio ranging from 0.2 to 1.5 and the Bcl-XL/Bax ratio ranging from 0.3 to 1.8. There was no correlation of mRNA levels with the apoptotic index. Immunohistochemical analysis showed positive Bcl-2, Bax, Bcl-XL expression in 20%, 72%, and 92% of cancer samples; however, their levels were variable. Spearman rank correlation coefficient test revealed a significant inverse association for the Bcl-XL IHC score and apoptotic index (P < 0.05). In contrast, Bcl-2, Bax protein levels did not show any association with the apoptotic index. However, as compared with the normal pancreas, Bcl-2, Bcl-XL, Bax were overexpressed in most of the pancreatic cancer samples (Mann-Whitney U test, P < 0.01). Conclusion: In pancreatic cancer, there is an upregulation of all the apoptotic regulatory molecules and the apoptotic index is chiefly determined by Bcl-XL protein levels.

Correlation of cytokine expression with rabies virus distribution in rabies encephalitis

Rabies encephalitis is a significant health hazard, particularly in Asia. To understand the role of immune mechanisms and cytokines in rabies encephalitis, we performed a retrospective and prospective study on the autopsy material. Representative histopathological sections were studied and subjected to immunostaining for rabies virus antigen, TNF-alpha and IL-1beta. Immunohistochemistry for IL-1beta and TNF-alpha revealed expression of these cytokines in 96% of cases in microglial cells, macrophages and lymphocytes with a strong positive correlation between IL-1beta and TNF-alpha immunopositivity and degree of perivascular and parenchymal inflammation. In addition, expression of IL-1beta and TNF-alpha also correlated positively with each other. However there was no direct correlation of viral antigen load with grading of cytokine expression. These findings indicate that IL-1beta and TNF-alpha together may play an important role to coordinate the dramatic inflammatory response associated with the rabies-encephalopathy. They may serve as important targets for future therapy.

Cranial chordoma in the first decade

Cranial chordomas are extremely rare in childhood with only 25 cases having been reported in the first decade of life. A 6-year-old female child with cranial chordoma is reported. Literature on the subject is reviewed, with special reference to the management, histopathological features and prognosis in childhood chordomas as compared to the adult variety.

Cardiac botryomycosis: an autopsy report

Visceral botryomycosis is rare, and documented sites are lung, brain, kidney, liver and prostate. This report describes a rare autopsy case of disseminated visceral botryomycosis, with bulky, grape-like botryomycotic vegetations in the heart, and similar abscesses in the lungs and bone marrow. This is the first such report in the literature to the best of our knowledge.

Vascular complications of tuberculous meningitis: An autopsy study

AIMSnVascular complications have the most serious consequences in patients with tuberculous meningitis (TBM). Although stroke is seen in approximately 20% of patients with TBM, the underlying vascular damage and infarction are much more extensive. This study has been undertaken to study the pathology at different levels of cerebral vessels and their resultant complications in TBM.nnnMATERIALS AND METHODSnFifty-one postmortem TBM brains were examined over a period of 16 years (1997-2012). The vascular pathology was studied in detail. Changes in middle cerebral artery (MCA) and basilar artery (BA) and their branches at different levels were analyzed in all cases.nnnRESULTSnThe age of the patients ranged from 3 months to 72 years. Infarcts were found in 37 cases, among which they were grossly visible in 27 cases. Macroscopic infarcts were more common in MCA territory whereas microscopic infarction was more in BA distribution-brainstem and cerebellum. Vascular involvement was almost universal, with smaller branches of both MCA (94%) and BA (100%) carrying the brunt of the disease, whereas the larger branches were variably involved. Infiltrative lesions were most common at all levels; necrotizing lesions were more common in smaller branches, whereas proliferative changes were seen more in larger branches.nnnCONCLUSIONnThis study showed extensive damage of cerebral vessels in TBM, which was responsible for the presence of widespread infarctions. Microscopic infarctions in the brainstem and cerebellum were much more common than reported by radiological studies. Thus, more aggressive management of TBM is required to combat its vascular complications.

Melanotic clear cell epithelioid angiomyolipoma: a rare entity and a mimic of clear cell renal carcinoma.

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Mycotic Aneurysm and Subarachnoid Hemorrhage Following Tubercular Meningitis in an Infant With Congenital Tuberculosis and Cytomegalovirus Disease

We describe autopsy findings in a 5-month-old infant with disseminated tuberculosis and congenital cytomegalovirus disease. The infant manifested with tubercular meningitis complicating as ruptured mycotic right middle cerebral artery aneurysm. Infiltrative, proliferative, and necrotizing vascular pathologies have been described; however, the occurrence of these is dependent on the duration of illness. The vessel pathology appears to be a payback of its immersion in the local inflammatory cell–rich exudates. Strokes early in the course of the disease are believed to be a consequence of vasospasm, and those occurring later during the disease course are due to proliferative intimal disease. Intracranial mycotic aneurysm following tubercular meningitis developing at such a young age has not been reported in the literature. The lung lesions in a congenitally transmitted tuberculosis and cytomegalovirus disease have also been elaborated.

A comprehensive examination of Smad4, Smad6 and Smad7 mRNA expression in pancreatic ductal adenocarcinoma

BACKGROUNDnSmad4, Smad6 and Smad7 are important molecules in TGF-beta pathway, which plays an important role in pancreatic ductal adenocarcinoma (PDAC) biology. Aims : This study examined the expression profiles of Smad4, Smad6 and Smad7 mRNA in patient samples of PDAC and their relationship to Smad protein expression, SMAD4 gene mutations, clinicopathological parameters and patient survival.nnnSETTINGS AND DESIGNnSurgically resected, paired normal and tumor tissues of 25 patients of PDAC were studied.nnnMATERIALS AND METHODSnProtein and mRNA levels were assessed by immunohistochemistry and RT-PCR, respectively.nnnSTATISTICAL METHODSnStatistical analysis was done using Students t-test, Pearsons chi-square test, Spearmans Rank Correlation, Pearsons Correlation test and Kaplan-Meier Logrank test.nnnRESULTSnWhile there was a highly significant difference in the protein levels of all three Smads in tumor as compared to normal samples, mRNA levels were significantly different only for Smad4. Protein levels did not correlate significantly with mRNA levels for any of the three Smads. The mRNA levels of Smad4 and Smad6, Smad4 and Smad7, and Smad6 and Smad7 in tumor samples showed a significant positive correlation. The relationship of Smad4 mRNA expression to SMAD4 gene status and Smad4 protein expression was discordant and there was no significant correlation between mRNA expression and clinicopathological parameters and patient survival.nnnCONCLUSIONnThe absence of concordance between SMAD4 gene status, mRNA expression and Smad4 protein expression suggests the presence of other regulatory mechanisms in Smad4 transcription and translation in PDAC.