Usha Agrawal

Role of Tumor Suppressor and Angiogenesis Markers in Prediction of Recurrence of Non Muscle Invasive Bladder Cancer

Non muscle invasive bladder cancers recur frequently and identification of biomarkers for predicting recurrence are necessary. The present study evaluated the individual and synergistic effects of tumor suppressor (p53/p21waf1) and angiogenesis [vascular endothelial growth factor (VEGF)/endoglin (CD105)] markers. The study included 90 cases of non muscle invasive bladder cancer. Cell spots were stained with primary antibodies and Flourescein isothiocyanate (FITC). Slides were observed under confocal laser scanning microscope for protein expression. The association between the markers individually and synergistically with recurrence were assessed by a χ2 and Fisher’s Exact test. Survival analysis was performed to predict recurrence and test for significant difference in recurrence free survival probability. Recurrence [overall:39(43.3%) and low grade(LG):26(54.2%)] was significant with p53 and VEGF expression and the profiles p53/VEGF, p53/CD105, VEGF/CD105, p53/p21/CD105, p53/VEGF/CD105 and all four were significantly associated with recurrence in both groups. In the multivariable model the [HR(95%CI),p: overall and LG] profiles p21/VEGF [2.195(1.052-4.582),0.036; 3.425(1.332-8.811),0.011], VEGF/CD105[2.624(1.274-5.403),0.009 and 3.380(1.348-8.472),0.009], p53/p21/CD105 [2.000(0.993-4.027),0.052 and 2.539(1.047-6.157),0.039], p53/VEGF/CD105 [2.360(1.148-4.849),0.020 and 2.738(1.104-6.788),0.030], p21/VEGF/CD105 [2.611(1.189-5.731),0.017 and 3.946(1.530-10.182),0.005] and all four [2.382(1.021-5.556),0.045 and 3.572(1.287-9.911),0.014] significantly predicted the recurrence along with significant log rank. In the pTa subset (n = 33) the profiles p53/p21, p53/CD105, p21/VEGF, VEGF/CD105, p53/VEGF/CD105, p53/p21/CD105 and p21/VEGF/CD105, significantly predicted hazard for recurrence. The present study emphasizes an underlying association between tumor suppressor (p21waf1) and angiogenesis (VEGF/CD105) biomarkers. In addition combination profiles appeared to indicate an aggressive nature with high propensity for recurrence in LG and pTa tumours.

Thickness of glomerular and tubular basement membranes in preclinical and clinical stages of diabetic nephropathy

Aims: This study aimed to elucidate the early renal changes in diabetes mellitus (DM) with and without clinical symptoms related to renal damage. Methods: Renal biopsy was studied in 25 patients (14 with microalbuminuria and 11 with albuminuria) both by light and electron microscopies (LM and EM, respectively) for renal changes and morphometry was performed to study glomerular and tubular basement membranes (GBM and TBM, respectively) width using a Soft Imaging System GmBH (analysis 3). Results: A significant increase was noted in the mean GBM and TBM thickness in both the preclinical and clinical groups compared to the control group. The changes in the TBM were noted to be predominant in both preclinical and clinical patients. Conclusions: This study indicates the importance of morphometric evaluation of the GBM and TBM width in the elucidation of early renal damage in diabetic nephropathy, especially in the absence of LM changes. The significance of identification of early renal changes using morphometric techniques for better management of these patients requires further studies.

Exosomal protein interactors as emerging therapeutic targets in urothelial bladder cancer

BACKGROUND Exosomes are rich sources of biological material (proteins and nucleic acids) secreted by both tumor and normal cells, and found in urine of urinary bladder cancer patients. OBJECTIVE The objective of the study was to identify interacting exosomal proteins in bladder cancer for future use in targeted therapy. METHODS The Exocarta database (www.exocarta.org) was mined for urinary bladder cancer specific exosomal proteins. The urinary bladder cancer specific exosomal proteins (n=248) were analyzed to identify enriched pathways by Onto-tool Pathway Express (http://vortex.cs.wayne.edu/ontoexpress). RESULTS Enriched pathways included cellular architecture, motility, cell to cell adhesion, tumorigenesis and metastasis. Proteins in the 9 top-ranked pathways included CTNNA1 (alpha-catenin), CTNNB1 (beta-catenin), VSAP, ITGA4, PAK1, DDR1, CDC42, RHOA, NRAS, RHO, PIK3AR1, MLC1, MMRN1, and CTTNBP2 and network analysis revealed 10 important hub proteins and identified inferred interactor NF2. CONCLUSIONS The importance of identifying interactors is that that they can be used as targets for therapy, for example, using Bevacizumab (avastin--an angiogenesis inhibitor) against NF2 to inhibit protein-protein interactions will inhibit tumor growth and progression by hindering the exosome biogenesis.

Malignant melanoma and basal cell carcinoma of the face: a rare coexistence.

The simultaneous presence of two disparate neoplasms occurring in the same specimen has been well documented, albeit uncommonly. The juxtaposition of malignant melanoma (MM) and basal cell carcinoma (BCC) as collision tumors has been rarely reported, with most cases describing melanoma in situ and BCC. We report a case of a 20-year-old male presenting with three papillomatous growths on the face, localized over the left frontotemporal region, below the right eye and over the right eyebrow. On histopathology and immunohistochemistry the lesions were diagnosed as pigmented MM and BCC. MM and BCC presenting at different sites on the face in the same patient along with a focus of metastasis in the same anatomical region as the primary tumor is quite rare. To the best of our knowledge this is the first report of such a case.

Leydig cell tumor: An unusual presentation

Leydig cell tumor is a benign tumor of the testis and malignant transformation, if present, is rare. The case presented here showed certain features of malignancy but no infiltration beyond the capsule or metastasis. The case could not be labeled as benign or malignant and patient is on follow-up. Differential diagnosis and clinical implications of a case in the borderline zone are discussed.

Squamous cell carcinoma arising in unilateral Warthin's tumor of parotid gland

Warthins tumor is a well-defined benign salivary gland neoplasm consisting of both epithelial and lymphoid components. Malignant transformation is extremely rare and the differential diagnosis of metastasis of an epidermoid carcinoma to Warthins tumor is important. We present a case with squamous cell carcinoma arising in unilateral Warthins tumor of parotid gland in a 16-year-old female patient.

Collision of malignant melanoma and squamous cell carcinoma in rectum: first report of a rare tumor

The term collision tumor is used to describe two neoplasms occurring in the same anatomic location with juxtaposition of different tumor elements. Such a coexistence of tumors anywhere in the body is relatively rare. We report a case of 32-year-old female with collision tumor of rectum. The tumor showed two distinct histological patterns with predominant component consisting of malignant melanoma and a minor component of squamous cell carcinoma. The morphological picture of collision was further confirmed by specific immunohistochemical profile of the two tumors. Collision tumors of rectum are uncommon with most of the reported cases comprising adenocarcinoma and neuroendocrine tumors. To the best of our knowledge this is the first case of collision tumor of malignant melanoma and squamous cell carcinoma in the rectum.

Association of Systemic Lupus Erythematosus and Beta Thalassaemia Trait- A Case Report.

Systemic Lupus Erythematosus (SLE) is a multisystem chronic inflammatory disease of autoimmune aetiology. It has a predilection for female gender and presence of photosensitive rash over the sun exposed area gives a clue to the diagnosis. Diagnosis in a male patient with atypical manifestations is unusual and difficult. A 25-year-old male presented with fever, fatigue, vomiting, abdominal pain and loss of weight. He had sustained injury on his right arm following which he developed abscess at the trauma site and severe anaemia. Further evaluation revealed pancytopenia and peritonitis. Though peritonitis is rare in SLE, it was considered in the differential diagnosis after ruling out bacterial and tubercular peritonitis. Positive anti-dsDNA and antiSm antibodies confirmed the diagnosis. While evaluating for microcytic anaemia it was found that iron studies were normal and A2 fraction was raised in haemoglobin electrophoresis. The symptoms and laboratory parameters improved remarkably with steroid therapy. Beta thalassaemia trait is rare in patients with SLE, but when they co-exist the manifestations can be severe. High degree of suspicion is required to diagnose SLE in male patients in absence of typical photosensitive rash. Beta thalassaemia trait often does not require any treatment except genetic counseling. However empirical treatment with iron should be avoided.

Unusual Presentation of Light Chain Deposition Disease: A Case Report.

Light Chain Deposition Disease (LCDD) is a rare disease characterized by deposition of monoclonal non-amyloid light chains in multiple organs. We report an unusual histologic manifestation of LCDD in a 55-year-old female patient, who presented with nephrotic syndrome and an increased serum creatinine. This case of LCDD had features of cast nephropathy on biopsy which is diagnostic of myeloma kidney, when the patient was clinically asymptomatic. Serum electrophoresis showed no abnormal band. There was no other evidence of a B-cell clonal disorder or amyloidosis. Following chemotherapy, improvement in renal function correlated with a reduction in circulating light-chain levels.

Clear cell odontogenic carcinoma of maxilla: A diagnostic challenge

Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic tumor which occurs mostly in the mandible. It is primarily seen in fifth to seventh decades with a female predilection. We report a case of CCOC in the maxillary arch of a 66-year-old woman. Morphologic examination along with histochemical and immunohistochemical markers led to the establishment of the diagnosis. It is important to diagnose this entity and differentiate it from other clear cell tumors in the head and neck region as it is a locally aggressive tumor with a propensity for regional, nodal, and distant metastasis.