PubMed Health⌕ Search

Biomedical subjects

D Marrano

Publications and source records attributed to D Marrano.

At least 37 records · Page 2Linked to original sources

Differentiation pathways in primary invasive breast carcinoma as suggested by intermediate filament and biopathological marker expression.

The expression of intermediate filament proteins (IFPs) in 65 primary breast carcinomas was analysed by a panel of specific antibodies. Results were integrated with the oestrogen and progesterone receptor (ER and PGR) status, Ki-67 marking, and epidermal growth factor receptor (EGFr) expression. Invasive breast carcinomas could be divided into three main groups: group 1 revealed positivity only for 'simple epithelial' cytokeratins (CKs 7, 8, 18, and 19); group 2 also stained with the antibodies K8.12 and 34 beta E12; while group 3 showed co-expression of CKs 14 and 17, vimentin, and alpha-smooth muscle actin. Group 3 consistently comprised tumours with the highest Ki-67 levels, EGFr positivity, and ER-PGR negative status. On the other hand, groups 1 and 2 usually exhibited a positive hormonal status, lower proliferative activity, and EGFr negativity. The results of this study indicate that the determination of IFPs can significantly contribute to the identification of groups of patients with different biopathological settings and possibly different clinical behaviour.

Biomarkers, Tumor↗

Multiple expression patterns of biopathological markers in primary invasive breast carcinoma: a useful tool for elucidating its biological behaviour.

BACKGROUND: Commonly used clinical and morphologic criteria have been reported to be of limited value in predicting the outcome of malignant tumours of the breast. Integrated information from the quantitative analysis in tumour tissue of biological parameters such as oestrogen and progesterone receptors (ER and PGR), proliferative activity, and proto-oncogene p53, c-erB2, and bcl-2 expression, may be useful for defining the biology of growth of breast carcinoma and to plan effective therapeutic strategies. PATIENTS AND METHODS: Immunohistochemistry with antibodies recognizing ER, PGR, Ki-67, and the p53, c-erbB2, and bcl-2 encoded proteins was performed on 291 primary breast carcinomas. Results were integrated with clinico-pathological indicators and examined with multivariate statistical procedures and modeling. RESULTS: P53, c-erbB2, and bcl-2 gene products were detected, respectively, in 30.6%, 31.6%, and 85.9% of the examined invasive breast carcinomas, revealing variable associations with cellular differentiation and proliferation as defined by ER/PGR status, Ki-67, tumour mass and histologic and nuclear grading. A multivariate graphical display on a subset of the most informative cases revealed that bcl-2 expression parallels ER/PGR status and is of importance in separating tumour clusters with different degrees of aggressiveness. CONCLUSIONS: The results of this study indicate that multivariate explorative analyses conducted on biological and clinico-pathological parameters might constitute an integrated approach to data analysis useful for distinguishing different biological behaviours and therapeutic groups in breast carcinoma. Our findings also suggest that bcl-2 expression may play a pivotal role in tumours lacking ER-mediated growth regulation.

Adult↗

Dieulafoy's disease associated with early gastric cancer.

In the past different terms have been used to define the vascular malformations of Dieulafoy's disease--for example, calibre persistent artery of the stomach, cirsoid aneurysm and gastric atherosclerosis. A case of Dieulafoy's disease is described in a 41 year old man, who presented with symptoms of anaemia and melaena, with particular attention paid to the morphological characterisation of the vascular histological lesions. Intimal hyperplasia with a non-concentric proliferation of myointimal cells, areas of muscular degeneration, aspects of vascular neoformation of the arterial wall, and other findings are reported. An association between an early diffuse adenocarcinoma and parietal anomalies of Dieulafoy's disease is illustrated.

Adult↗

Alcoholic liver disease in alcoholic chronic pancreatitis: a prospective study.

The prevalence and characteristics of alcoholic liver disease (ALD) in patients with alcohol-induced chronic pancreatitis (AICP) are not well defined. Fifty consecutive patients undergoing surgery for AICP were investigated for evidence of ALD. In addition to preoperative functional and imaging assessment of the liver, all had liver biopsy during surgery. Hepatic biopsy results were as follows: 12 patients had normal liver and 10 minimal aspecific changes; of the remaining 28 patients, 7 had liver cirrhosis, 11 showed features of alcoholic hepatitis, 2 had moderate steatosis, 6 extrahepatic cholestasis, and the remaining 2 had a combination of alcoholic hepatitis and cholestasis. Of the 7 patients with cirrhosis, 3 had oesophageal varices and 2 of these developed ascites in the postoperative period; in the remaining patients with ALD, this disease was subclinical. Patients with ALD consumed significantly (p < 0.005) more alcohol than those without ALD. In patients with cirrhosis, the duration of alcohol consumption (mean 27.6 years, range 18-42 years) was significantly longer (p < 0.05) than in patients without ALD (mean 19.7 years, range 8-36 years). The association of ALD with AICP is much more common than previously believed. The fact that AICP occurs earlier than liver cirrhosis and the fact that many patients stop alcohol consumption after the first attacks of pancreatic pain may explain, at least in part, the apparent rarity with which this association has been indicated by previous studies.

Adolescent↗

Intraductal papillary-mucinous neoplasm of the pancreas. A clinicopathologic entity.

AIMS: The main clinicomorphologic findings from two new cases of intraductal papillary-mucinous neoplasm of the pancreas were analyzed and discussed. METHODS: Formalin-fixed pancreatic tissues from the more representative areas were routinely stained. An electron microscopic examination was performed in case 2 on glutaraldehyde-fixed tissue fragments. RESULTS: Both patients had a long history of symptoms that was suggestive of chronic pancreatitis. At endoscopic retrograde pancreatography a dilatation of the main duct was observed. Ultrasonography revealed cystic dilatations that were interpreted as pseudocysts. The patients underwent total pancreatectomy. The gross appearance showed no mass, but the pancreas was enlarged and diffusely hard. The cut surface showed micromacrocysts filled with soft friable tissue and mucus. Histological examination revealed diffuse neoplastic papillary proliferations within ectatic and cystically dilated ducts. The lesions exhibited varying grades of atypia and foci of in situ carcinoma. No clear evidence of invasion or lymph node metastases were observed. The nontumorous pancreas showed diffuse and multiple hyperplastic papillary changes in the ductal tree. CONCLUSION: The main clinicopathologic findings of intraductal papillary-mucinous neoplasm of the pancreas have been reported. Our study favors the hypothesis that chronic pancreatitis and/or ductal epithelial papillary hyperplasia may play a role in the pathogenesis of this tumor. We have emphasized the cystic appearance and mucinous features of this neoplasm, and so we suggest the use of the term intraductal papillary-mucinous neoplasm.

Cystadenoma, Mucinous↗

Expression of intermediate filaments in normal and neoplastic exocrine pancreas.

The intermediate filament (IF) proteins present in the normal and pathological exocrine human pancreas were studied by immunolocalization using antibodies to cytokeratins (CKs) and vimentin. Acinar cells of normal pancreas showed a presence of simple CKs 8 and 18. Duct epithelium consistently expressed CKs 7, 8, 18 and 19 whereas centroacinar cells were rather low in CK 7. A subpopulation of CK 4 cells was detected in inter-intralobular ducts. In addition, some ducts contained individual cells or groups of cells that were positive for the stratification-related CKs (CKs 4, 5, 13, 15, 16). All pancreatic ductal adenocarcinomas regularly expressed CKs 7, 8, 18, 19 and were also positive for the 34 beta E12 antibody. Cytokeratin 4 was detected in a minor population of tumor cells. Pancreatic carcinoma also contained minor amounts of stratification-related CKs in variable combinations. Mucinous cystoadenocarcinoma showed the presence of CKs 7, 8, 18, 19 and was also positive for 34 beta E12, whereas the serous microcystic tumor presented CKs 8, 18, 19 and a variable amount of CKs 4 and 7. The duct-ductular alterations of the exocrine pancreas contained a different combination and distribution of CK isoforms similar to normal pancreatic ductal system. Mucinous hypertrophy and pyloric gland metaplasia reacted with antibodies to CKs 7, 8, 18 and 19. Vimentin was focally present both in normal and neoplastic tissue. Our results indicate that pancreatic ducts are characterized by an intrinsic "biliary-pancreatic duct type" immunoprofile (CKs 7, 8, 18 and 19), in contrast to acinar cells expressing exclusively CKs 8 and 18. We also detected a subpopulation of ducts regularly expressing CK 4. Surprisingly, several stratification-related CKs were detected both in normal and neoplastic exocrine pancreas. Moreover, the differentiation phenotypes of pancreatic tumors were reminiscent of normal cellular compartments.

Adenocarcinoma↗

Lysozyme localization in normal and diseased human gastric and colonic mucosa. A correlative histochemical, immunohistochemical and immunoelectron microscopic investigation.

The distribution of lysozyme in normal and pathological human gastric and colonic mucosa was studied by light and electron microscopic immunocytochemical techniques and compared with histological and histochemical features. Lysozyme was localized in pyloric glandular epithelial cells, mucous neck cells of fundic glands, Paneth cells and some crypt cells of the mature colonic mucosa. In addition, lysozyme was detected in a large spectrum of "immature" or "regenerative" epithelium: neck cells of the gastric regenerative zone, undifferentiated columnar cells of surface and hyperplastic interfoveolar crests of the stomach, regenerative cells in a healed gastric ulcer, some goblet cells in incomplete intestinal metaplasia, cells of the regenerative zone at the bottom of colonic crypts and, finally, fetal intestinal epithelium. Electron microscopically, we localized lysozyme in the central core of mucous granules in the pyloric gastric glandular epithelium and in the dense mucous granules in gastric mucous neck cells. Lysozyme was also detected in some immature mucin-producing cells of the gastric regenerative zone and in the rough endoplasmic reticulum of surface hyperplastic columnar gastric cells. At the electron microscopic level, a peculiar correlation between the immunopattern of lysozyme and the morphology of mucous granules has been postulated. All our data support and extend the view that the presence of lysozyme may be related to cell immaturity as well as to a regenerative state of the cell. Finally, the lysozyme distribution and its relation to mucosubstances in gastric and colonic carcinoma suggest that lysozyme should not be considered an exclusive marker of cells of gastric derivation.

Adenocarcinoma↗

Parathyroid gastrin and parathormone-producing tumour in the Zollinger-Ellison syndrome of MEN 1 origin.

A case of Zollinger-Ellison syndrome of multiple endocrine neoplasia type 1 (MEN 1) origin with hyperparathyroidism and with a rise in serum gastrin due to an unusual parathyroid "gastrinoma" has been investigated. The patient had multiple endocrine tumours (pituitary and parathyroid), but no evidence of pancreatic or duodenal gastrin-producing neoplasm. Radio-immunoassay, immunohistochemistry and electron microscopy showed gastrin in one parathyroid adenoma. These findings, together with a decrease of gastrinaemia after parathyroidectomy suggest that true gastrin was produced by parathyroid tumour cells and that they themselves may be the origin of the hypergastrinaemia. Our ultrastructural investigation extends these observations and the results are discussed.

Adenoma↗

Diagnosis of islet cell tumor by means of endoscopic ultrasonography.

A 31-year-old man with recurrent attacks of hypoglycemia was hospitalized with the clinical suspicion of an insulinoma. Computed tomography and conventional (transabdominal) ultrasound were doubtful, showing a small solid low-density mass probably originating from the tail of the pancreas. Selective angiography and transhepatic venous sampling for pancreatic hormone assay were not discriminant. Finally, an endoscopic ultrasonographic examination, allowing a better visualization of the pancreas, established with certainty the origin of the lesion from the tail of the gland. This was subsequently confirmed at operation.

Adenoma, Islet Cell↗

Management of a large mediastinal cyst of thyroid origin.

Large mediastinal cysts of the thyroid are rare and it is difficult to make a definitive tissue diagnosis prior to surgical removal. Ultrasonography and computed axial tomography are useful in documenting the cystic nature of the lesion and demonstrating its relationship to other mediastinal structures. These studies may also suggest the tissue of origin. We report a case of massive mediastinal thyroid cyst situated in the right posterior mediastinum and causing significant tracheal compression. Because of this unusual location and lack of iodine uptake, preoperative diagnosis was not possible. At surgery, which we performed via right thoracotomy because of the location of the mass, its origin from thyroid tissue was demonstrated. Resection was accomplished with care taken not to injure the recurrent laryngeal nerve. The patient recovered uneventfully.

Diagnostic Imaging↗

The use of somatostatin in acute pancreatitis--results of a multicenter trial.

This study involves a multicenter trial aimed at evaluating the comparative beneficial therapy of somatostatin and traditional symptomatic therapy in the management of acute pancreatitis. According to our final data somatostatin has not proved to be any better than traditional medical treatment. Nevertheless, in our opinion, the advantage of a single and expeditious therapy makes somatostatin administration preferable to the combined employment of several therapeutic measures usually applied in these circumstances.

Acute Disease↗

Expression of UDP-GalNAc:NeuAc alpha 2,3Gal beta-R beta 1,4(GalNAc to Gal) N-acetylgalactosaminyltransferase involved in the synthesis of Sda antigen in human large intestine and colorectal carcinomas.

N-Acetylgalactosamine beta 1,4-linked to a galactose residue substituted in O-3 with one N-acetylneuraminic acid residue is the immunodominant sugar of the human blood group Sda antigen which is also largely present in the kidney medulla and colon mucosa. A beta 1,4-N-acetylgalactosaminyltransferase very similar to that previously described in urine of Sd(a+) individuals (F. Serafini-Cessi, N. Malagolini, and F. Dall'Olio. Arch. Biochem. Biophys., 266: 573-582, 1988) has been identified in cells released from human large intestine. The higher values of beta 1,4-N-acetylgalactosaminyltransferase activity were detected in proximal and medial segments of the large intestine, suggesting a proximal-distal gradient of the enzyme expression. When the beta 1,4-N-acetylgalactosaminyltranferase activity of colorectal carcinoma specimens from 18 patients was compared with that of the normal mucosa surrounding the tumor, a constant and in several cases drastic reduction of the activity was detected in tumor cells. Three human colorectal adenocarcinoma cell lines (Colo-205, SW-48, and SW-948) have been found to lack the beta 1,4-N-acetylgalactosaminyltransferase activity. Altogether, these results support the notion that the malignant transformation drastically affects the expression of this glycosyltransferase in large bowel cells.

Antigens, Tumor-Associated, Carbohydrate↗

Increased CMP-NeuAc:Gal beta 1,4GlcNAc-R alpha 2,6 sialyltransferase activity in human colorectal cancer tissues.

The sialyltransferase activities of 10 human colorectal specimens were compared with those of the corresponding adjacent normal mucosa. Using asialofetuin as an acceptor we found, in tumor tissues of 9 out of 10 patients, an increased sialyltransferase activity towards the N-linked chains as determined upon peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase (PNGase) treatment. On the contrary, the activity towards the O-linked chains was not significantly changed. When the specificity of the sialyltransferase acting on N-linked chains was investigated by using N-acetyl-lactosamine (Gal beta 1,4GlcNAc) as an acceptor, we found that the alpha 2,6 sialyltransferase activity expressed by both normal and tumor colorectal tissues was far higher than the alpha 2,3-activity and that alpha 2,6 was the only sialyltransferase activity increased in tumor tissues. Kinetic analysis revealed that normal and tumor alpha 2,6 sialyltransferases have the same apparent Km for the acceptor substrate (469 and 465 microns), but normal enzyme has a higher Km for CMP-NeuAc (303 microns) than the tumor enzyme (50 microns). The higher affinity of tumor enzyme for the nucleotide-sugar might partially explain its increased activity in tumor tissues. In addition, tumor tissues contain a lower amount of sialic acid despite the increase in alpha 2,6 sialyltransferase activity.

Asialoglycoproteins↗