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M Papotti

Publications and source records attributed to M Papotti.

At least 91 records · Page 5Linked to original sources

Value of Ki-67 immunostaining in preoperative biopsies of carcinomas of the lung.

In lung carcinomas, the proliferative activity, as detected by Ki-67 antigen immunostaining of surgical specimens, is a valuable factor predicting clinical evolution and response to treatment. We investigated whether bronchial endoscopic and fine-needle aspiration (FNA) biopsies of lung carcinoma can provide a reliable estimation of the tumor proliferative fraction (TPF). In 66 resectable lung carcinomas, sections of preoperative bronchial or FNA biopsies and the corresponding surgical specimens were stained in parallel for Ki-67 using MIB-1 monoclonal. The mean TPF was 44.7% in the surgical specimens, 40.3% in bronchial biopsies, and 26.3% in FNAs. When the scores of biopsy and resected specimen of each individual tumor were compared, a significant correlation between the TPFs of preoperative and postoperative specimens was found (r = .79). In both biopsy and surgical specimens, a high TPF was associated with squamous cell carcinoma histological type and high-grade (poorly differentiated) tumors. In addition, a significantly (P < .05) lower disease-free interval was found in patients affected by highly proliferating tumors (irrespective of the tumor stage). We conclude that the proliferative activity of lung cancer can be reliably assessed in bronchial or FNA biopsies. This information could help to select chemotherapy protocols in nonresectable lung carcinomas.

Aged↗

Retrieved endogenous biotin: a novel marker and a potential pitfall in diagnostic immunohistochemistry.

AIM: Antigen retrieval (AR) procedures are based on the effect of heating (by either microwave or pressure cooking treatments) on routinely fixed and paraffin embedded tissues. We observed that AR procedures restore the reactivity of endogenous biotin (EB) and report on the distribution of EB following AR in a series of routinely fixed and embedded tissues. METHODS AND RESULTS: Following pressure cooking or microwave treatments, a simple streptavidin-peroxidase staining revealed retrieved endogenous biotin (REB) in normal tissues (such as liver, kidney and adrenal cortex), in oxyphylic cells and in some tumours, especially in carcinomas of the kidney and of the adrenal cortex. In formalin-fixed (but not in alcohol-fixed) tissue sections, the heating procedures caused an intense and finely granular cytoplasmic reaction, following a routine streptavidin-conjugated peroxidase treatment. The staining was prevented by blocking of EB by a sequential avidin-biotin treatment. CONCLUSIONS: Retrieval of EB reactivity can cause pitfalls in diagnostic immunohistochemistry but, alternatively, it might also constitute a useful and novel diagnostic marker.

Antigens↗

Immunophenotypic heterogeneity of hyalinizing trabecular tumours of the thyroid.

AIMS: We studied 12 cases of hyalinizing trabecular tumour of the thyroid gland (HTT) with the aim of reviewing the cytological, histological and immunophenotypic features and of investigating the relationships of HTT with other thyroid neoplasms. METHODS AND RESULTS: Eleven patients were female and one male, aged 8-74 years (median 58). Ten cases had a benign behaviour, while two cases were locally aggressive. Of the latter, one developed distant metastases and the other is a recent case. All patients are alive 6-311 months after diagnosis. Cytologically, HTT was characterized by hypercellular smears with aggregates of roundish cells having features of papillary carcinoma (nuclear grooves, vacuoles) and fragments of fibrous tissue. Histologically, prominent nesting, trabecular growth patterns and a hyaline stroma (partly positive for laminin and collagen type IV) were found. One case was associated with a papillary microcarcinoma. Two additional cases had extensive areas of papillary carcinoma. In one of these, hyalinized papillary stalks were observed. All tumours contained thyroglobulin but not calcitonin. High molecular weight cytokeratin (a marker of papillary carcinoma) was focally positive in 4/12 cases only and thyroperoxidase (a marker of follicular adenomas, but not of papillary carcinoma) was found in 3/12 cases. CONCLUSIONS: The immunophenotypic profile and the morphological features suggest that HTTs are an heterogeneous group of tumours, some of them probably representing variants of papillary carcinoma with hyalinized stroma.

Adenoma↗

Relationship between hepatocyte proliferation and hepatitis delta virus replication in neoplastic and non-neoplastic liver tissues.

We studied the relationship between hepatocyte proliferation and hepatitis delta virus (HDV) replication at the single cell level. The proliferating cell nuclear antigen (PCNA) (by immunohistochemistry) and the HDV RNA (by in situ hybridization) were stained in neoplastic and non-neoplastic liver tissues of 19 patients with chronic HDV infection, including four cases of cirrhosis with superimposed hepatocellular carcinoma (HCC). As controls, we assessed the hepatocyte proliferation of liver tissues from 16 patients with chronic hepatitis B and on three normal livers. The hepatocyte PCNA labelling index of HDV-infected tissues was comparable with that seen in chronic hepatitis B-infected livers but was significantly higher than that observed in normal livers. Although cirrhotic tissues had lower hepatocyte proliferating fractions than non-cirrhotic tissues, the difference was not statistically significant. The hepatocyte proliferation rate did not correlate with the level of intrahepatic HDV replication or with the histological activity. In double-labelling experiments, PCNA and HDV RNA staining did not co-localize, with the exception of two of three cirrhotic tissues associated with HCC, where the association between the two markers was statistically significant. This co-localization was not observed, however, in the adjacent tumorous tissues. In patients with chronic HDV infection the hepatocyte proliferation was increased with respect to normal liver tissue, but was comparable with that observed in patients with chronic hepatitis B virus infection and did not correlate with the level of HDV replication or the histological activity. In the cirrhotic tissue of patients with HCC (but not in the tumour counterpart), HDV RNA may occasionally co-localize with the marker of hepatocyte proliferation. Whether this association between viral replication and cell division is related to liver carcinogenesis remains to be established.

Carcinoma, Hepatocellular↗

A combined hepatocellular/cholangiocellular carcinoma with sarcomatoid features.

A case of primary liver cancer showing combined hepatocellular and cholangiocellular features and an associated pseudosarcomatous (schwannomatous) component is presented. Histologically, compact microtrabecular and glandular patterns in a dense fibrous stroma were recognized. The latter showed transition towards spindle cell sarcomatous growth in several areas of both the primary and the lymph-node metastasis. Glandular areas expressed acidic mucins and AE1-reactive keratins; albumin mRNA was detected by in situ hybridization in both trabecular and glandular areas. Vimentin and S-100 protein were mostly expressed in the pseudosarcomatous areas. Both the morphological patterns and the phenotypic features indicate that divergent differentiation along both epithelial and mesenchymal lineages took place in this rare primary liver tumor.

Albumins↗

Oxytocin and oxytocin-analogue F314 inhibit cell proliferation and tumor growth of rat and mouse mammary carcinomas.

The effects of oxytocin (OT) and the OT-analogue F314 were investigated an xenografts of mouse mammary and colon carcinomas (TS/A and C26 tumors) and of rat mammary carcinoma (D-R3230AC). In all cases, proliferation was previously assessed by cell counting in cultured cell lines, whereas tumor growth was checked by serial measures of tumor volume and by evaluation of tumor weight at the end of the experiment. Both cell proliferation and tumor growth were inhibited by OT and F314. These data support previous observations on the inhibitory effect of OT and F314 on the growth of MCF7, T47D and MDA-MB231 human breast cancer cell lines and open new prospects for testing the effect of this hypothalamic hormone and its analogues on the control of breast carcinoma growth.

Animals↗

Poorly differentiated oxyphilic (Hurthle cell) carcinomas of the thyroid.

A series of 60 cases of oxyphilic (Hurthle cell) carcinomas (HCC) of the thyroid were reviewed to determine whether it is possible to correlate morphologic and clinical features as a means of assessing prognosis. Twenty cases showing predominant solid or trabecular patterns (as described in poorly differentiated carcinomas with a follicular pattern) were selected and the clinicopathological features were investigated. Based on cell size, two groups of solid or trabecular HCCs were identified: The first group (17 cases) was made up of typical large granular oxyphilic cells, and the second (three cases) had small oxyphilic cells. All tumors were reactive for thyroglobulin and for a mitochondrial antigen, selectively marking oxyphilic, mitochondrial-rich cells. Nuclear pleomorphism in individual cells was a common feature, but foci of anaplastic carcinoma were never found. Four cases overexpressed p53 protein and 10 expressed bcl-2 gene product. At follow-up, among the high-stage (pT3-pT4) tumors, seven patients had recurrences or metastases, six of whom were alive with disease or died of disease. In the control group of HCC with predominant follicular patterns, only one of 40 cases had a fatal outcome. The difference was statistically significant. Small-cell patterns and a p53 protein-positive/bcl-2 gene product negative phenotype were features of clinically aggressive HCC cases. We suggest that within the spectrum of oxyphilic (Hurthle cell) tumors, poorly differentiated HCC showing solid or trabecular patterns are a distinct group, based on both morphological and clinical features.

Adenocarcinoma↗

Perianal cytomegalovirus ulcer in an HIV-infected patient.

A 51-year-old man with acquired immunodeficiency syndrome presented with a perianal ulcer. Histologically there were numerous cytomegalic inclusions within endothelial cells and stomal fibroblasts. Cytomegalovirus within infected cells was demonstrated by immunohistochemistry and in situ hybridization. No cytopathic typical of Herpes simplex were detected. The ulcer resolved completely after a treatment with ganciclovir.

AIDS-Related Opportunistic Infections↗

[Acute suppurative thyroiditis. Report of a case and review of the literature].

The authors present a case of acute suppurative thyroiditis complicated by acute dyspnoea with asphyxia in a patient of geriatric age. In this patient there were present possible infectious focuses like multiple dental abscesses and contamination of the urinary tract. Histological examination highlighted a focus of papillifer carcinoma in the context of the gland. We have a review of the literature on this observation and description. Acute suppurative thyroiditis is currently a pathology of rare observation. This rarity is due, apart from the availability of antibiotic therapy, to an intrinsic resistance of the thyroid gland to contamination. In most cases we are talking of bacterial infections, but in immunodepressed subjects fungal etiology is noteworthy. The infection could arise from primitive focuses present in any bodily district with propagation to the thyroid across different ways. Expressive is the anamnestic observation of preexisting thyroid dysfunction. After an attentive evaluation of the clinical findings, usually characteristic, it is important to complete the diagnostic course with some instrumental investigations. In particular cervical sonography, possibly associated with agobiopsy is fundamental. Initially therapy is medical (basically antibiotic). The surgical resolution foresees the drainage of the purulent abscess or the thyroidectomy if it is associated with a struma.

Acute Disease↗

Ectopic aldosteronoma associated to another adrenocortical adenoma in the adrenal gland of the same side.

The occurrence of tumors originating from aberrant adrenocortical tissue in ectopic site is very rare. Up to now only two cases of ectopic aldosterone-producing adenoma have been described. We have observed another case of ectopic aldosteronoma, located in the retrocaval region, laterally to the body of the 12th thoracic vertebra. This ectopic tumor was associated to another adrenocortical adenoma, in the adrenal gland of the same side. The diagnostic implications of this observation are discussed.

Adenoma↗

Proliferative activity in parathyroid tumors as detected by Ki-67 immunostaining.

Clear morphological criteria for differentiating benign from malignant parathyroid tumors are not yet available and unfavorable prognosis cannot be predicted by histopathological parameters alone. A retrospective study of a series of parathyroid lesions was designed to evaluate the diagnostic role of the cell cycle-associated Ki-67 antigen detected by MIB-1 monoclonal immunocytochemistry. The mean tumor proliferative fraction (TPF), expressed as the number of Ki-67-positive nuclei per 1,000 cells, was 0.8 in normal parathyroid glands (nine specimens), 26.0 in hyperplasias (11 specimens), 32.8 in adenomas (11 specimens), and 60.5 in a group of tumors with histological features consistent with carcinoma (12 specimens). The difference between the latter two values was statistically significant (P < .05). When the five most clinically aggressive tumors were considered, the difference was even more remarkable (TPF, 78.6; P < .001). Oncocytic and pleomorphic cell components were found to proliferate with a labeling pattern similar to that of the chief cells. We conclude that proliferative activity is an additional useful parameter for evaluating parathyroid tumors diagnostically. Aggressive behavior may be expected in those tumors with a TPF greater than 6%.

Adenoma↗

Diagnostic problems in medullary carcinoma of the thyroid.

Medullary carcinoma of the thyroid (MCT), the tumor entity related to parafollicular C cells of the thyroid gland, is characterized by peculiar morphological, functional and behavioral features. Apart from the constant finding of calcitonin production by MCT, heterogeneous patterns of growth as well as different associations with other lesions in the setting of MEN II syndrome have been observed. This review addresses these points, as were discussed at the 1992 European School of Pathology courses. Heterogeneity of histological patterns of MCT suggests caution in the interpretation of any thyroid tumor. Immunohistochemical demonstration of calcitonin is apparently the only valid criterion for a differential diagnosis. A correct identification of MCT is important for the individual patient (to plan proper therapy) but also for patient's relatives to screen other familiar cases in the setting of MEN II syndromes.

Carcinoma, Medullary↗

Prolactin receptors in human pituitary adenomas.

OBJECTIVE: In the rat, prolactin receptors (PRL-R) have been identified in normal pituitary cells and in anterior pituitary tumours induced by oestradiol. No published data are available concerning PRL-R in the human pituitary. The aim of our study was therefore to detect the presence of PRL-R in the normal human pituitary gland and human pituitary adenomas. DESIGN: Evaluation of free and total PRL-R in the normal pituitary gland and different pituitary tumours characterized by immunocytochemical analysis. PATIENTS: Twenty-six unselected patients (14 M, 12 F) who underwent surgery for pituitary adenoma (3 prolactinomas, 4 GH-PRL adenomas, 5 GH adenomas, 1 ACTH adenoma, 9 glycoprotein and/or alpha-subunit adenomas, 4 null cells adenomas) were studied. Nine pituitaries from subjects whose death was unrelated to brain and endocrine diseases, were also studied as a control group in the PRL binding studies. MEASUREMENTS: Free PRL-R in microsomal membranes were determined by in-vitro radioreceptor assay using 125I-labelled human PRL as ligand. Total PRL-R were also measured in the same membrane fractions by removing endogenous PRL bound to its receptors using 4 M MgCl2. Serum PRL levels were also evaluated in all patients before surgery using an IRMA method. RESULTS: Specific binding values for PRL (free PRL-R) were 0.39 +/- 0.03% (range 0-1.96%) in the pituitary adenomas. These binding values were identical to those observed in normal pituitaries (0.38 +/- 0.07%, range 0.1-0.78%). Elevated PRL binding (1.25% and 1.96%) was found in two patients with PRL secreting adenomas and very high serum PRL levels (5768 and 11240 mU/I. No PRL binding was shown in 4 patients. Treatment of membranes with 4 M MgCl2 increased the specific binding (total PRL-R) in both pituitary tumours (0.5 +/- 0.11%; P < 0.001) and normal pituitaries (0.47 +/- 0.07%; P < 0.02). CONCLUSIONS: Our data have demonstrated the presence of prolactin receptors in normal cadaveric pituitary and in most pituitary adenomas, irrespective of histological classification. In particular, elevated prolactin receptor levels were shown in PRL-secreting tumours from patients with markedly increased serum PRL levels. Our study may support several lines of experimental evidence for a specific functional role for PRL in the growth of some pituitary adenomas.

Adenoma↗

Intranodular reactive endothelial hyperplasia in adenomatous goitre.

Endothelial hyperplasia has rarely been recognized in the thyroid. Ischaemic events or hemorrhage, sometimes as a result of fine needle aspiration procedures, have been regarded as possible causes. To clarify the morphological pattern and the clinical significance of this lesion, we studied a series of adenomatous goitres and selected 11 cases showing prominent endothelial hyperplasia in an individual nodule. Grossly, the parenchyma of the affected nodule was substituted by greyish, friable tissue surrounded by a fibrous capsule and by a thin rim of residual thyroid parenchyma. Microscopically, fibrinous and haemorrhagic material was crossed by intercommunicating vascular channels or papillary structures. These were lined by plump endothelial cells. In only one case had pre-operative fine needle aspiration biopsy been performed: smears yielded a haemorrhagic background, fibrin and numerous elongated cells; colloid and follicular cells were virtually absent. In both surgical and cytological specimens a differential diagnosis with a vascular neoplasm, a rare occurrence in the thyroid, was taken into consideration. We conclude that intranodular reactive endothelial hyperplasia is a relatively common occurrence (1.6%) in adenomatous goitre and is of diagnostic interest in both surgical and cytological specimens, since it can mimic vascular tumours and may lead to unnecessary treatment if misdiagnosed.

Endothelium↗

Chromogranin gene expressions in colorectal adenocarcinomas.

Presence of neuroendocrine (NE) cells identified by argyrophilia and presence of NE markers, such as the chromogranins) is a common event (15 to 51% of the cases) in colorectal adenocarcinomas. The nature and significance of these cells, scattered in variable number within the neoplastic population, is unclear. Twenty-five cases of colorectal adenocarcinomas were investigated in parallel by immunocytochemical and hybridization (Northern blot) procedures to detect presence of three members of the chromogranin family, i.e., Chromogranin A, Chromogranin B, and Secretogranin II/secretoneurin and their synthetic machinery. The results indicate discrepancies between presence of immunoreactive cells and expression of the related specific mRNA molecules. Interestingly, such discrepancies were more remarkable for Chromogranin A than for Chromogranin B and Secretogranin II. Taking into account all three types of chromogranins, only a few cases provided the same results at the mRNA and protein levels investigated respectively by Northern blot and immunohistochemistry. The spectrum of observed events is therefore wider and more complex than hitherto believed. Our interpretation is that transient activation of NE differentiation genes can be a common and extensive event in neoplastic stem cells. In a few postmitotic cells, expression of NE genes would lead to cytoplasmic accumulation of NE markers and regulatory peptides, retained even after the switching off of the genes. This hypothesis might be valid for various mixed exocrine-endocrine patterns observed in carcinomas of different organs (gastrointestinal tract, pancreas, prostate, breast, lung).

Adenocarcinoma↗