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Biomedical subjects

J Rode

Publications and source records attributed to J Rode.

At least 19 recordsLinked to original sources

Expression and processing of gastrin in pancreatic adenocarcinoma.

BACKGROUND: Gastrin is a trophic hormone and promotes growth of gastrointestinal and non-gastrointestinal cancers. Studies both in vitro and in vivo have suggested that pancreatic cancer cells not only have the ability to respond to circulating forms of gastrin but also to respond to the autocrine production of gastrin and its precursors. The aim of this study was to identify the expression of CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin in both normal pancreas and pancreatic adenocarcinoma. METHODS: Tissue sections from patients with normal pancreas (n = 10) and pancreatic cancer (n = 22) were assessed using immunohistochemical methods for CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin expression. RESULTS: Normal pancreas showed no expression of receptor or gastrin isoforms except for occasional cells in the islets. Definite expression of CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin was observed in 95, 91, 55 and 23 per cent of sections from patients with pancreatic cancer respectively. CONCLUSION: Pancreatic cancer cells express CCK-B/gastrin receptor and gastrin precursor forms in most patients. Expression of the gastrin precursor forms is probably related to autocrine production. New therapeutic strategies need to be developed for the management of pancreatic cancer. Targeting gastrin and its receptor may provide a novel treatment option.

Adenocarcinoma↗

Expression and processing of gastrin in hepatocellular carcinoma, fibrolamellar carcinoma and cholangiocarcinoma.

BACKGROUND/AIMS: Gastrin is a trophic factor within the normal gastrointestinal tract and is also a mitogen for a number of gastrointestinal and non-gastrointestinal tumours. Precursor forms of gastrin including progastrin (proG) and glycine-extended gastrin (G-gly) as well as the fully processed amidated gastrin (G-NH2) are expressed by tumours. There has been little study of the role of gastrin in either normal liver or liver tumours. The aim of this study was to identify the expression of CCK-B/gastrin receptor (CCK-BR), proG, G-gly and G-NH2 in normal liver and liver tumours. METHODS: Tissue sections from patients with hepatocellular carcinoma, fibrolamellar carcinoma, cholangiocarcinoma as well as normal liver biopsies were assessed for expression of CCK-BR and gastrin isoforms. RESULTS: Most liver tumours express CCK-BR and are able to process gastrin as far as proG and G-gly, although not as far as the amidated form. There appears to be little expression of the receptor and no expression of precursor forms of gastrin in normal liver. CONCLUSIONS: Liver tumours express the CCK-BR and precursor forms of gastrin. This expression may be associated with tumour proliferation.

Bile Duct Neoplasms↗

Discrimination between benign and malignant melanocytic skin lesions by multivariate analysis, quantitative S-100 immunohistochemistry, nuclear morphometry and DNA cytometry.

OBJECTIVE: To determine whether combined quantitative immunohistochemistry of S-100, nuclear morphometry and DNA image cytometry improves discrimination between benign and malignant melanocytic skin lesions (MSLs). STUDY DESIGN: S-100 protein expression was measured in tissue sections of MSLs using an image cytometry system. Localized areas of high S-100 expression were used to identify regions in sequential, facing sections in which morphometric and cytometric features of nuclei, including DNA ploidy, were also measured. RESULTS: Malignant cases had significantly higher S-100 protein staining intensity, larger nuclei and greater DNA content (P < .05). High staining intensity for S-100 protein weakly correlated with variation in size of the mean nuclear area (P = .04) and DNA content (P = .03). Combining the features of nuclear area and DNA integrated optical density in areas of high-intensity staining for S-100 protein discriminated more accurately between 12 benign and 16 malignant areas than any of the features along (P = .0003). CONCLUSION: Combined multivariate quantitative immunohistochemical, morphometric and DNA cytometric analysis greatly improves discrimination between benign MSLs and malignant melanoma. Larger test sets are required to confirm the promising results of this initial study.

Cell Nucleus↗

Helicobacter pylori in ectopic gastric mucosa in Meckel's diverticulum.

We report a case of a 25-year-old man who presented with a large rectal bleed and positive Meckel's scan followed by surgical excision of a Meckel's diverticulum. The diverticulum was lined by gastric body type mucosa showing evidence of active chronic gastritis associated with the presence of Helicobacter pylori organisms, these being identified immunohistochemically with a specific polyclonal antibody. We have reviewed another 21 cases of Meckel's diverticula removed at St Vincent's Hospital between 1984 and 1997: in nine of these cases the diverticulum was lined by ectopic gastric body type mucosa and in one of these there was an active chronic gastritis associated with Helicobacter pylori. There has been considerable controversy regarding both the presence and significance of Helicobacter organisms in Meckel's diverticula. This is the first study to use immunohistochemistry specifically to identify Helicobacter pylori within two cases of Meckel's diverticula. Both cases demonstrated an active chronic gastritis present within the gastric body type mucosa, thus suggesting that the organisms play a pathogenic role.

Adult↗

Vulvar Merkel cell tumor with glandular and squamous differentiation.

A case of a Merkel cell tumor of the vulva is presented. In addition to the typical microscopic, immunohistochemical, and ultrastructural features of Merkel cell tumor, there were areas of squamous and glandular differentiation. This is the ninth reported case of a vulvar Merkel cell tumor, and the first where squamous and glandular differentiation were seen. The findings support an origin of Merkel cell tumors from pluripotential stem cells.

Adenocarcinoma↗

Detrusor myopathy: an accurate predictor of bladder hypocompliance and contracture in interstitial cystitis.

OBJECTIVE: To determine whether any histological characteristics within the detrusor in cases of early interstitial cystitis (IC) predict the subsequent development of severe symptoms due to bladder contracture. PATIENTS AND METHODS: The detrusor muscle component of bladder biopsies from 21 patients with IC was examined in sections stained with haematoxylin and eosin. Videocystometrography was performed at least 2 months after the biopsy and the patients were then followed up clinically for at least 3 years. RESULTS: The detrusor appeared normal in 13 patients; in eight there was evidence of detrusor myopathy. Patients with biopsies confirming detrusor myopathy were significantly more likely to have hypocompliant bladders than those with normal detrusor muscle histology (P < 0.02). Over the following 3 years, six of the eight patients with detrusor myopathy developed progressively severe symptoms and required subtotal cystectomy and enterocystoplasty. None of the 13 patients without detrusor myopathy required bladder substitution. CONCLUSION: In IC, detrusor myopathy is associated with bladder hypocompliance. Patients with detrusor myopathy appear to have more severe disease and are more likely to progress to bladder contracture requiring substitution enterocystoplasty.

Contracture↗

Massive amyloid deposition in pancreatic vipoma: a case report.

We present a case of a pancreatic islet cell tumor, demonstrating typical clinical and immunohistochemical characteristics of a VIPoma, but with the novel feature of massive stromal amyloid deposition. Amyloid deposition has been reported in association with insulinomas of the pancreas, but as far as the available literature suggests, it has not been reported in VIPomas. Islet associated polypeptide (IAPP) and calcitonin are both candidates for the amyloidogenic peptide in this case, based on observations in other tumors.

Aged↗

Primary lymphoma of the ampulla of Vater.

A 57-year-old woman was investigated for obstructive jaundice with endoscopic retrograde cholangiopancreaticography that showed a tumor at the ampulla of Vater. A Whipple's procedure was performed. A protuberant tumor was present at the ampulla of Vater in the background of multiple mucosal polyps in the duodenum. Light microscopy revealed a diffuse non-Hodgkin's lymphoma with centrocytelike cells forming lymphoepithelial lesions and infiltrating the sphincter of Oddi. The duodenal polyps were hyperplastic lymphoid follicles with reactive germinal centers. Immunohistochemical staining characterized the tumor as a B-cell neoplasm with IgA heavy-chain and lambda light-chain restrictions. Complete remission of the disease occurred after surgery. The clinical, histologic, and immunohistochemical features of this lymphoma are suggestive of histogenetic derivation from mucosal-associated tissue.

Ampulla of Vater↗

Aneuploid islet cell tumor with late metastasis.

An unusual case of insulin producing islet cell tumor is reported which recurred after a 16 yr interval. In most instances malignancy of islet cell tumors is impossible to assess morphologically or functionally but depends on the recognition of metastases. Nuclear DNA analysis provides significant prognostic and biological information in a number of solid human tumors. Retrospective computerized nuclear image analysis of the primary tumor in the present case showed an aneuploid DNA profile similar to that seen in the metastasis. It appears that ploidy studies may be useful in predicting malignant potential of islet cell tumors.

Adenoma, Islet Cell↗

Overexpression of heat shock protein (hsp) 70 associated with abnormal p53 expression in cancer of the pancreas.

Heat shock proteins (hsp) are involved in degradation or chaperoning nascent and abnormal proteins to various subcellular locations. p53 tumour suppressor gene overexpression and mutation occur frequently in pancreatic cancers. Mutant p53 proteins produced in cancers of other sites have been found to form complexes with hsp 70. Consequently, binding to hsp 70 may be used to indicate the presence of mutant p53 proteins. The presence of hsp 70 was investigated by immunohistochemistry in core biopsies of 42 adenocarcinomas of the pancreas (well differentiated, N = 1 and moderate to poorly differentiated, N = 41). Four cases of islet cell tumours were included in the study. These neoplasias were compared with biopsies of chronic pancreatitis (N = 9) and normal pancreas (N = 5). The majority of adenocarcinomas, 24/42 (57%), showed expression of both hsp 70 and p53. None of the islet cell tumours or cases of chronic pancreatitis showed p53 and hsp 70 coexpression. Only 1 (20%) of the normal pancreas showed concurrent nuclear immunostaining for p53 and cytoplasmic immunostaining for hsp 70. The high proportion of pancreatic adenocarcinoma showing immunoreactivity for both hsp 70 and p53 may indicate high mutation rate of the p53 gene in this tumour. Further studies using molecular techniques are required to elucidate the nature of both hsp and p53 genes in pancreatic cancers.

Adult↗

Distribution of type IV collagen in pancreatic adenocarcinoma and chronic pancreatitis.

Changes in the basement membrane are present in various neoplastic conditions such as neurofibrosarcoma, cervical carcinoma, colorectal cancers and hepatoblastoma. This study examines the expression of type IV collagen in the basement membrane, using an immunohistochemical method, in the normal pancreas (n = 10), chronic pancreatitis (n = 15) and pancreatic adenocarcinoma (n = 30). The formalin fixed, paraffin embedded tissue was sectioned and pretreated with protease prior to immunostaining for type IV collagen. There was a statistically significant difference in type IV collagen expression between pancreatic carcinoma and chronic pancreatitis (P = 0.0001; chi 2 test with continuity correction). In pancreatic adenocarcinoma, type IV collagen distribution in the basement membrane was discontinuous and irregular or absent around individual or groups of neoplastic cells (n = 30). Most cases of chronic pancreatitis showed continuous pattern of basement membrane type IV collagen around residual ducts (n = 10). In the normal pancreas, only one of the ten cases showed discontinuous basement membrane around pancreatic ducts, while in the rest of the cases, the pattern was continuous. This study suggests that there is abnormal distribution of type IV collagen in the basement membrane in pancreatic carcinoma, which may be related to either abnormal deposition or degradation of the collagen. Immunostaining for type IV collagen may be of some diagnostic use for distinguishing pancreatic adenocarcinoma from problematic cases of chronic pancreatitis.

Adenocarcinoma↗

Malignant potential of aneuploid pancreatic endocrine tumours.

Evaluation of the malignant potential of pancreatic endocrine tumours is difficult by histological criteria alone. Nuclear deoxyribonucleic acid (DNA) cytometric analysis can provide significant prognostic and biological information in a number of solid human tumours. Thus, the DNA profiles and nuclear parameters of 39 patients with pancreatic endocrine tumours diagnosed from 1969 to 1989 were studied, using computerized video image analysis. Of the 39 patients with tumours, 27 cases did not have evidence of metastatic disease at the time of investigation. The majority of these (N = 21) showed a diploid profile. Five were aneuploid and one was tetraploid. In the 12 tumours that proved malignant, three had tissue of both primary tumour and the metastases analysed; six had material only from the primary tumour, although metastatic disease was established clinically; and another three only had tissue from the secondary tumour studied. The majority of the malignant cases were aneuploid (N = 7); three were diploid; one showed a diploid primary but an aneuploid secondary, and one showed a hyperdiploid pattern. The percentage of nuclei with a DNA content greater than 5N (5CER) did not seem to contribute further to the assessment nor did the means of the nuclear areas and shape factors. It appears that ploidy studies may be useful in predicting malignant potential of pancreatic endocrine tumours. There is a high rate of immunostaining for insulin by benign pancreatic endocrine tumours and this may be a useful adjunct to distinguish them from their malignant counterparts. However, there is no statistically significant correlation between the expression of various hormones and the DNA ploidy of tumour cells.

Aneuploidy↗

Proliferating cell nuclear antigen (PCNA) in pancreatic adenocarcinoma.

Interpretation of pancreatic biopsy material can pose substantial difficulties, particularly in the presence of chronic pancreatitis where ductular changes and fibrosis may mimic adenocarcinoma. We examined whether differences in cell kinetics could aid in the distinction between pancreatic carcinoma and chronic pancreatitis. Pancreatic tissue was obtained by percutaneous ultrasonographic guided biopsy. There were a total of thirty-four cases comprising patients with chronic pancreatitis (N = 11) and those with adenocarcinoma (N = 23). The cell cycle activity was determined in sections of routinely paraffin-processed, formalin-fixed biopsy material using immunohistochemical stains for the monoclonal proliferating cell nuclear antigen antibody PCNA (PC 10), a 36 kd nuclear protein synthesized in the late G 1 and S phase. After calculating the PCNA index (% of positively staining nuclei compared to total number of nuclei counted) these were compared in the conditions studied. The PCNA indices in chronic pancreatitis were low with a mean of 5%, while those of adenocarcinoma were 53% (p < 0.001). In conclusion, the PCNA index in pancreatic adenocarcinoma is significantly higher than in chronic pancreatitis. Determination of the PCNA index may be helpful as an adjunct in the diagnosis of problematic cases.

Adenocarcinoma↗

Cystic hamartoma of the renal pelvis.

We describe three hitherto undocumented cases of renal lesion in the adult age group that share a similar site and histological features. They are three adult women, with a short clinical history of pain and an abdominal mass. A partial or complete nephrectomy resulted in clinical cure. All cases showed an intrarenal multicystic mass situated adjacent to the pelvicalyceal system. These vaguely circumscribed lesions had no true capsule and blended in with the adjacent renal parenchyma. The histological appearance was distinctive and characterised by disorderly biphasic proliferation of epithelial and mesenchymal elements. The epithelial component consisted of tubules and cysts lined by cuboidal and columnar epithelium showing focal oncocytic changes. The stroma was cellular and predominantly fibroblastic with scattered bundles of smooth muscle cells. Despite extensive sampling, blastemal cells were not identified. The tubular epithelium was positive for CAM 5.2, epithelial membrane antigen, carcinoembryonic staining, and vimentin immunostaining. The stroma stained positively for vimentin and smooth muscle bundles for alpa smooth muscle actin and desmin. The cytological appearances of these lesions were benign. We propose that these are benign hamartomatous lesions arising as a result of faulty focal embryogenesis. They are distinct from well recognised lesions such as multilocular cysts, partially differentiated nephroblastomas, mesoblastic nephromas, and nephrogenic adenofibromas.

Adult↗

Immunocytochemical characterization of neuroendocrine tumours of the larynx.

Twenty-two neuroendocrine tumours of the larynx were investigated using a panel of immunocytochemical markers. Three were small cell carcinomas, eight were large cell neuroendocrine carcinomas and 11 were paragangliomas. Twenty were positive for protein gene product 9.5, 19 for neuron-specific enolase, 15 for chromogranin A, nine for bombesin, eight for substance P, eight for neuropeptide Y, eight for metenkephalin, seven for somatostatin, five for calcitonin, eight for calcitonin gene-related peptide and one for vasoactive intestinal polypeptide. Bombesin immunoreactivity was largely restricted to the small cell carcinomas and large cell neuroendocrine carcinomas and neuropeptide Y, metenkephalin and substance P to the paragangliomas. This comprehensive immunocytochemical analysis of neuroendocrine tumours of the larynx demonstrates that these tumours represent special entities but have similar patterns of immunostaining to those of neuroendocrine tumours in other sites.

Adult↗

A comparison between radioligand and immunohistochemical assay of hormone receptors in primary breast cancer.

The detection of oestrogen and progesterone receptor (ER and PgR) levels in human breast carcinoma has traditionally been performed using a biochemical radioligand binding method. This method has several disadvantages including the requirement for generous tissue samples, the production of radioactive waste products and the inability to exclude non-malignant cellular material from the assay process. An alternative method for detecting hormone receptors is available with the use of a monoclonal antibody specific for the ER or PgR receptor using immunocytochemical assay (ER-ICA or PgR-ICA). Although designed for use on frozen section material, with modifications this method can be used on paraffin sections of routinely fixed and processed tissue, on archival material and on very small specimens. Further, an objective assessment or scoring of staining intensity is possible using computerized video-image analysis. Forty-three cases of primary breast carcinoma, treated from 1989 to 1991 at Goulburn Valley Base Hospital, Shepparton were assessed for ER and PgR content using both the radioligand method and immunohistochemistry with video-image analysis, and the results were compared. Of the 43 cases, ER-ICA and ER had a concordance of 81% (P < 0.001, r = 0.58) and in 39 cases, PgR and PgR-ICA had a concordance of 87% (P < 0.001, r = 0.54). Because the sample for radioligand assay is of uncertain composition and the immunohistochemical stain can be scored specifically for malignant epithelium, a degree of discordance is thought to be mostly attributable to the limitations of the radioligand assay.

Breast Neoplasms↗