Study of mutated p53 protein by immunohistochemistry in urothelial neoplasm of urinary bladder.

It is difficult to predict which urothelial neoplasm would subsequently recur or progress to muscle invasive tumours or produce metastasis.The aim and objective of the study were to evaluate the scope of immunohistochemical expression of p53 in human urothelial neoplasms with regard to grade, stage and outcome of the patients. Eighteen consecutive patients were taken and urothelial tumour samples were obtained from transurethral resection or surgical excision. Histopathological examinations were performed and the grading was done according to the WHO/ISUP consensus classification of urothelial neoplasms. Immunohistochemical staining for p53 was performed on formalin fixed paraffin embedded tissue sections with appropriate positive and negative control. It was found 3 patients with papillary urothelial neoplasm of low malignant potential (PUNLMP), 5 cases of papillary low grade urothelial carcinoma, 10 patients with papillary high grade urothelial carcinoma including 2 cases of invasive urothelial carcinoma. All three PUNLMP cases showed negative results. Four out of 5 low grade papillary urothelial carcinoma had nuclear p53 accumulation, while all of the 10 papillary high grade carcinoma had high p53 index. The finding of negative p53 staining in PUNLMPs and high p53 index in high grade papillary urothelial carcinomas and invasive carcinomas support the notion that mutation of p53 gene might be unrelated to the development of urothelial neoplasms but definitely play a crucial role in progression of the malignancy.

Kappa statistics in the screening of malignancy of prostate.

The optimal upper limit of the normal range for prostate specific antigen (PSA) is suggested, but review of literature reveals that, malignancy of prostate can occur below that range and some benign prostatic diseases are occasionally associated with higher levels. The aim of the study is for early detection of prostatic malignancy. We tried to evaluate digital rectal examination (DRE), estimation of PSA and transrectal ultrasound (TRUS) guided core needle biopsy and histopathological examination in the patients. Seventy-two consecutive patients with lower urinary tract symptoms were taken in this retrospective study from January 2005 to February 2006. PSA level was measured by automated chemilumininescence system. Prostatic biopsies were taken for histopathological examination and stained with haematoxylin and eosin. Gleason grading was applied in case of adenocarcinoma of prostate. For detection of malignancy, sensitivity, specificity, predictive value for positive test and of negative test, percentage of false negatives and false positives, p-values, confidence interval and kappa statistical calculations were done. It was found 19 cases with PSA level > 4 ng/ml had benign diseases of prostate and one person having PSA level < 4 ng/ml had adenocarcinoma of prostate. Seven DRE positive cases had benign disease of the prostate and 5 DRE negative patients had adenocarcinoma of prostate. When compared, serum total PSA value alone and combined PSA and DRE, the later combined approach was found to be more useful. We recommend the study of DRE, PSA and TRUS guided core needle biopsy for detection of prostatic cancer at localised and potentially curable stage.

Dopamine in vivo inhibits VEGF-induced phosphorylation of VEGFR-2, MAPK, and focal adhesion kinase in endothelial cells.

Vascular permeability factor (VPF)/VEGF is a potent multifunctional cytokine and growth factor that has critical roles in vasculogenesis and in both physiological and pathological angiogenesis. Because it has been recently shown that the neurotransmitter dopamine at pharmacological dose can inhibit VEGF/VPF-mediated microvascular permeability, proliferation, and migration of endothelial cells in vitro, we therefore hypothesized that endogenous dopamine may regulate the actions of VPF/VEGF in vivo. We report that VPF/VEGF-induced phosphorylation of VEGF receptor 2, focal adhesion kinase, and MAPK in the endothelial cells is strikingly increased in both dopamine-depleted and dopamine D(2) receptor knockout mice compared with normal controls, thereby indicating that endogenous dopamine regulate these critical signaling cascades required for the in vivo endothelial functions of VPF/VEGF. Together, these observations provide new mechanistic insight into the dopamine-mediated inhibition of the activities of VPF/VEGF and suggest that endogenous neurotransmitter dopamine might be an important physiological regulator of VPF/VEGF activities in vivo.

Ablation of peripheral dopaminergic nerves stimulates malignant tumor growth by inducing vascular permeability factor/vascular endothelial growth factor-mediated angiogenesis.

Many important physiological and pathological processes are modulated by angiogenesis. It has been shown that initiation of this angiogenic process is an essential early step in the progression of malignant tumors. We report here that ablation of peripheral dopaminergic nerves markedly increased angiogenesis, microvessel density, microvascular permeability, and growth of malignant tumors in mice. Endogenous peripheral dopamine acted through D2 receptors as significantly more angiogenesis and tumor growth was observed in D2 dopamine receptor knockout mice in comparison with controls. The vascular endothelial growth factor receptor 2 phosphorylation, which is critical for promoting angiogenesis, was also significantly more in tumor endothelial cells collected from the dopamine-depleted and D2 dopamine receptor knockout animals. These results reveal that peripheral endogenous neurotransmitter dopamine might be an important physiological regulator of vascular endothelial growth factor-mediated tumor angiogenesis and growth and suggest a novel link between endogenous dopamine, angiogenesis, and tumor growth.

Depleted dopamine in gastric cancer tissues: dopamine treatment retards growth of gastric cancer by inhibiting angiogenesis.

PURPOSE: It has been recently shown that the catecholamine neurotransmitter dopamine (DA) strongly and selectively inhibits vascular permeability factor/vascular endothelial growth factor (VPF/VEGF)-induced angiogenesis. Gastric cancer is highly angiogenic and is dependent on VEGF for its growth and progression. Because substantial amounts of DA present in normal stomach tissues has been implicated in several gastric functions, we therefore investigated the role, if any, of this neurotransmitter in the growth and progression of gastric cancer. EXPERIMENTAL DESIGN: Initially, the status of DA and tyrosine hydroxylase, the rate-limiting enzyme required for DA synthesis, were determined in human gastric cancer tissues and in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer tissues of rats. On the basis of our observation of inverse correlation between stomach DA and gastric cancer growth, we determined the effect of pharmacological dose of DA on the angiogenesis and growth of MNNG induced gastric cancer in rats and Hs746T human gastric cancer in nude mice. RESULTS: DA and tyrosine hydroxylase were absent in both human and rat gastric cancer tissues. On the contrary, a low nontoxic pharmacological dose of DA significantly retarded tumor angiogenesis by inhibiting VEGFR-2 phosphorylation in tumor endothelial cells, which expressed DA D(2) receptors. This action of DA was associated with the growth inhibition of both MNNG-induced rat malignant gastric tumors and xenotransplanted human gastric cancer in nude mice. CONCLUSIONS: Our study demonstrates that there is an inverse correlation between endogenous stomach DA and gastric cancer and indicates that DA already in clinical use for other purposes might have a role as an antiangiogenic agent in the treatment of gastric cancer.

Fine needle aspiration cytology of thyroid gland and histopathological correlation--revisited.

Fine needle aspiration of the thyroid gland, followed by cytological studies and their correlation with histopathological diagnosis have been undertaken to assess the effectiveness of fine needle aspiration cytology in diagnosing disorders of this gland. The cases in which discrepancies had arisen between these two methods of diagnosis have also been reviewed. Out of the total 100 patients studied, 28 were cases of simple colloid goitre, 17 of adenomatoid goitre, 10 of autoimmune thyroiditis ranging from lymphocytic thyroiditis to Hashimoto's thyroiditis, 28 of follicular neoplasia, 10 of papillary carcinoma, one of medullary carcinoma, 2 of anaplastic carcinoma and 4 of cystic lesions of the thyroid gland. Although, fine needle aspiration cytology of the thyroid gland was diagnostic in 75% of cases, it did not correlate with the histopathological diagnosis in the remaining 25% of cases. Possible reasons behind these discrepancies have been discussed.