Swarnalata Gowrishankar

Non diabetic renal disease in type 2 diabetes mellitus

Aim:  The aim of this analysis of renal biopsies in people with type 2 diabetes was to know the prevalence and nature of non‐diabetic renal disease (NDRD) and to note its correlation with the duration of diabetes, extent of proteinuria and presence or absence of retinopathy.

ARID1B, a member of the human SWI/SNF chromatin remodeling complex, exhibits tumour-suppressor activities in pancreatic cancer cell lines

Background:The human ATP-dependent SWItch/sucrose nonfermentable (SWI/SNF) complex functions as a primary chromatin remodeler during ontogeny, as well as in adult life. Several components of the complex have been suggested to function as important regulators of tumorigenesis in various cancers. In the current study, we have characterised a possible tumour suppressor role for the largest subunit of the complex, namely the AT-rich interaction domain 1B (ARID1B).Methods:We performed Azacytidine and Trichostatin A treatments, followed by bisulphite sequencing to determine the possible DNA methylation-induced transcription repression of the gene in pancreatic cancer (PaCa) cell lines. Functional characterisation of effect of ARID1B ectopic expression in MiaPaCa2 PaCa cell line, which harboured ARID1B homozygous deletion, was carried out. Finally, we evaluated ARID1B protein expression in pancreatic tumour samples using immunohistochemistry on a tissue microarray.Results:ARID1B was transcriptionally repressed due to promoter hypermethylation, and ectopic expression severely compromised the ability of MiaPaCa2 cells to form colonies in liquid culture and soft agar. In addition, ARID1B exhibited significantly reduced/loss of expression in PaCa tissue, especially in samples from advanced-stage tumours, when compared with normal pancreas.Conclusion:The results therefore suggest a possible tumour-suppressor function for ARID1B in PaCa, thus adding to the growing list of SWI/SNF components with a similar function. Given the urgent need to design efficient targeted therapies for PaCa, our study assumes significance.

PNUTS Functions as a Proto-Oncogene by Sequestering PTEN

PTEN is a well-defined tumor suppressor gene that antagonizes the PI3K/Akt pathway to regulate a multitude of cellular processes, such as survival, growth, motility, invasiveness, and angiogenesis. While the functions of PTEN have been studied extensively, the regulation of its activity during normal and disease conditions still remains incompletely understood. In this study, we identified the protein phosphatase-1 nuclear targeting subunit PNUTS (PPP1R10) as a PTEN-associated protein. PNUTS directly interacted with the lipid-binding domain (C2 domain) of PTEN and sequestered it in the nucleus. Depletion of PNUTS leads to increased apoptosis and reduced cellular proliferation in a PTEN-dependent manner. PNUTS expression was elevated in certain cancers compared with matched normal tissues. Collectively, our studies reveal PNUTS as a novel PTEN regulator and a likely oncogene.

Evidence for possible non-canonical pathway(s) driven early-onset colorectal cancer in India.

Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for >90% of late‐onset colorectal cancer (CRC). Our understanding of early‐onset sporadic CRC is however comparatively limited. In addition, most seminal studies have been performed in the western population and analyses of tumorigenesis pathway(s) causing CRC in developing nations have been rare. We performed a comparative analysis of early and late‐onset CRC from India with respect to common genetic aberrations including Wnt, KRAS, and p53 (constituting the classical CRC progression sequence) in addition to MSI. Our results revealed the absence of Wnt and MSI in a significant proportion of early‐onset as against late‐onset CRC in India. In addition, KRAS mutation frequency was significantly lower in early‐onset CRC indicating that a significant proportion of CRC in India may follow tumorigenesis pathways distinct from the classical CRC progression sequence. Our study has therefore revealed the possible existence of non‐canonical tumorigenesis pathways in early‐onset CRC in India.

A comparative study of cervical smears in an urban hospital in India and a population-based screening program in Mauritius.

OBJECTIVE To study cervical smear abnormalities in urban women in India and women in Mauritius and to compare the results in the two groups. STUDY DESIGN An analysis of 6010 cervical smears taken as part of routine check-ups in an urban hospital was done and an analysis of 10,000 cervical smears taken from women participating in a National Cancer Screening Program in Mauritius was done. Emphasis was put on cervical epithelial cell abnormalities and the results in the two populations are compared with that of similar studies in other parts of the world. RESULTS Non specific inflammation formed 19.6% and 25.34% of the smears in the Indian and Mauritian groups, respectively (with specific infection forming 6.05% and 15.08%). The epithelial abnormalities constituted 1.392% of the Indian group and 0.47% of the Mauritian group. The difference was statistically significant in the atypical squamous cells of uncertain significance (ASCUS) and atypical glandular cells of uncertain significance (AGUS) group. CONCLUSIONS The prevalence of low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) is similar to that in the developed world.

Olfactory ensheathing cell tumor

Olfactory ensheathing cells (OECs) are found in the olfactory bulb and olfactory nasal mucosa. They resemble Schwann cells on light and electron microscopy, however, immunohistochemical staining can distinguish between the two. There are less than 30 cases of olfactory groove schwannomas reported in the literature while there is only one reported case of OEC tumor. We report an OEC tumor in a 42-year-old male and discuss the pathology and origin of this rare tumor.

Desmoplastic fibroma of the frontal bone

Desmoplastic fibroma is a benign but locally aggressive tumor arising usually from the mandible, pelvis and long bones with a potential for recurrence. We report a case of desmoplastic fibroma of the frontal bone in a young male.

Banded Collagen in the Kidney with Special Reference to Collagenofibrotic Glomerulopathy

Background: The normal glomerular basement membrane, composed of type IV collagen, plays an important function in the process of filtration. Rarely, type III, type I, or type V collagen is seen in the glomerulus, resulting in three different types of non-immune mediated glomerulopathies recognized thus far. These are characterized by deposition of banded collagen fibers in the glomerulus. Methods: The authors reviewed 4934 kidney biopsies submitted over the past 5 years. Five of these revealed the presence of banded collagen in the glomeruli. Conclusion: Combined clinical and ultrastructural examination has led to a definitive diagnosis. These diseases exhibit indolent progression and as yet do not have specific treatment.

Gleason scoring of prostatic carcinoma: Impact of a web-based tutorial on inter- and intra-observer variability

A total of 40 cases of prostatic adenocarcinomas were scored independently by four pathologists using the Gleason scoring system. After attending a web-based tutorial, the scoring was repeated by all. Consensus scores were obtained by simultaneous viewing of each case in a multihead microscope by all four pathologists. The scores were then compared. The pretutorial kappa (kappa) values ranged from 0.36 to 0.64 with an average of 0.459. After the tutorial, the kappa values ranged from 0.44 to 0.678 with the average kappa value increasing to 0.538, thus indicating an improvement in the agreement. The intraobserver agreement ranged from 0.435 to 0.788. We conclude that web-based tutorials with emphasis on images developed by experts serve to achieve an uniformity in reporting.

Acute Kidney Injury Recognition in Low- and Middle-Income Countries.

Acute kidney injury (AKI) is increasingly common around the world. Because of the low availability of effective therapies and resource limitations, early preventive and therapeutic measures are essential to decrease morbidity, mortality, and cost. Timely recognition and diagnosis of AKI requires a heightened degree of suspicion in the appropriate clinical and environmental context. In low- and middle-income countries (LMICs), early detection is impaired by limited resources and low awareness. In this article, we report the consensus recommendations of the 18th Acute Dialysis Quality Initiative meeting in Hyderabad, India, on how to improve recognition of AKI. We expect these recommendations will lead to an earlier and more accurate diagnosis of AKI, and improved research to promote a better understanding of the epidemiology, etiology, and histopathology of AKI in LMICs.