Biomedical subjects

S La Rosa

Publications and source records attributed to S La Rosa.

At least 19 recordsLinked to original sources

PubMed2001

Immunohistochemical detection of fibroblast growth factor receptors in normal endocrine cells and related tumors of the digestive system.

Endocrine tumors (ETs) of the digestive system produce several growth factors including acidic and basic fibroblast growth factors (aFGF and bFGF, respectively), which are thought to be involved in the growth of tumor cells and in the proliferation of tumor stromal cells. Their actions depend on binding to four specific receptors--FGFR1, FGFR2, FGFR3, and FGFR4--whose distribution in normal endocrine cells and related tumors of the gastroenteropancreatic (GEP) system has previously been examined. Formalin-fixed, paraffin-embedded normal tissues and 60 well-characterized GEP endocrine tumors were immunostained using specific antibodies directed against various GEP hormones, aFGF, FGFR1, FGFR2, FGFR3, and FGFR4. Acidic FGF immunoreactivity (IR) was found in gut EC cells; FGFR1 immunoreactivity in rare duodenal endocrine cells and in pancreatic A cells; FGFR2 immunoreactivity in gastric and duodenal G cells, pancreatic B cells, and rectal EC cells; FGFR3 immunoreactivity in duodenal G cells; and FGFR4 immunoreactivity in rectal L cells and in pancreatic B, PP, and A cells. Immunoreactivity for at least one of the four FGFRs was found in all tumors, independently of FGFR expression in the putative cell of origin. EC cell tumors, which were all positive for aFGF, were found to express at least three different FGFRs. FGFRs also were localized in the stromal cells of all the tumors examined. The tumor stroma was more abundant in EC cell tumors than in other types of neoplasms. The results suggest that aFGF-FGFR interaction may be involved in the modulation of normal endocrine cell functions and in the regulation of tumor growth and stromal proliferation of EC cell carcinoids.

Adolescent↗

PubMed2001

Expression of acidic fibroblast growth factor (aFGF) and fibroblast growth factor receptor 4 (FGFR4) in breast fibroadenomas.

BACKGROUND/AIM: Fibroadenomas are benign tumours composed of both glandular and fibrous tissue. The mechanisms regulating the growth of these tumours and the relation between the stromal and epithelial cells are poorly understood. Acidic fibroblast growth factor (aFGF) is a well known fibroblast activator, which acts through four specific cell surface receptors, among which, fibroblast growth factor receptor 4 (FGFR4) is highly specific. The aim of this study was to evaluate the distribution of aFGF and FGFR4 in specific cell types of fibroadenomas to understand their possible role in the growth of these breast lesions. METHODS: Formalin fixed and paraffin wax embedded tissues from 15 fibroadenomas and peritumoral normal breasts were investigated for the expression of aFGF and FGFR4 using immunohistochemistry. The presence of aFGF mRNA was also investigated using in situ hybridisation. RESULTS: Immunoreactivity for aFGF and FGFR4 was seen in epithelial cells, but it was lacking in myoepithelial cells of both normal tissues and fibroadenomas. Strong FGFR4 immunoreactivity was found in stromal fibroblasts, which were also weakly positive for aFGF. aFGF mRNA was detected in epithelial cells and in some stromal fibroblasts. CONCLUSIONS: These results suggest a paracrine/autocrine modulation of epithelial and stromal cells of fibroadenomas through an aFGF-FGFR4 interaction. This interaction might regulate various cell functions and the growth of fibroadenomas.

Adolescent↗

PubMed2001

[Diagnostic criteria and classification of gastro-intestinal pancreatic endocrine tumors].

In this presentation the gastrointestinal pancreatic endocrine tumors (ETs) are subdivided into well differentiated ETs and poorly differentiated ETs. Well differentiated ETs are subclassified into ETs with benign behavior, ETs with uncertain behavior and well differentiated endocrine carcinomas. The criteria allowing a distinction among these main types of neoplasms are listed according to the site of origin of the ETs. In addition, the main functional types of ETs of the pancreas, stomach, duodenum, jejunum, ileum, appendix and large bowel are briefly described.

Cell Differentiation↗

PubMed2000

Detection of gonadotropin-releasing hormone receptor in normal human pituitary cells and pituitary adenomas using immunohistochemistry.

Gonadotropin-releasing hormone (GnRH), which is a well-known regulator of gonadotroph function, has recently been considered to be a paracrine factor involved in the control of somatotroph, lactotroph, and corticotroph cells. GnRH action is initiated by binding to a specific cell surface receptor, the gonadotropin-releasing hormone receptor (GnRHR), which is expressed by follicle-stimulating hormone/luteinizing hormone (FSH/LH) cells. Using in situ hybridization techniques, GnRHR messenger ribonucleic acid (mRNA) has recently been detected in normal human anterior pituitary gland and in various pituitary adenomas, including FSH/LH-cell, growth hormone (GH)-cell, adrenocorticotropic hormone (ACTH)-cell, and null-cell adenomas. However, immunohistochemical studies indicating the specific cell distribution of GnRHR in normal pituitary cells have never been reported. The aim of the present investigation was to evaluate the immunohistochemical expression of GnRHR in different types of normal pituitary cells and related tumors. Using double-label immunohistochemical techniques on formalin-fixed and paraffin-embedded tissues and specific antibodies directed against pituitary hormones and GnRHR, we found GnRHR immunoreactivity not only in FSH/LH cells, but also in GH- and thyroid-stimulating hormone (TSH) cells. GnRHR was detected in FSH/LH-cell, GH-cell, mixed GH- and prolactin (PRL)-cell, and alpha-subunit (alpha-SU)/null-cell adenomas. The findings of this study suggest that the interaction between GnRH and GnRHR may play a role in paracrine/autocrine regulation of different types of normal pituitary cells and pituitary adenomas.

Adenoma↗

PubMed2000

Localization of inhibin/activin subunits in normal pituitary and in pituitary adenomas.

The localization of inhibin/activin (I/A) subunits was investigated in human normal adenohypophysial cells and in 87 pituitary adenomas of different types, using immunohistochemistry. Monoclonal antibodies directed against alpha, beta A and beta B subunits of I/A were employed. In normal pituitary, alpha subunit of inhibin was detected only in FSH-positive gonadotrophs, while beta A subunit of I/A was expressed in FSH-positive gonadotrophs, GH-cells and in a few PRL-cells. beta B subunit was found in FSH-positive gonadotrophs, TSH-cells and a few LH-positive gonadotrophs. The three subunits of I/A were detected in the majority of nonfunctioning tumors, while functioning adenomas showed a significantly lower expression. This study shows that alpha, beta A and beta B subunits of I/A are expressed by specific adenohypophysial cell types and that they are characteristically present in nonfunctioning adenomas. These results suggest that inhibins and activins may play a role in the local regulation of pituitary hormonal secretion both in normal adenohypophysial cells and in pituitary adenomas.

Activins↗

PubMed2000

Mixed mucus-secreting and oncocytic carcinoma of the thyroid: pathologic, histochemical, immunohistochemical, and ultrastructural study of a case.

We report a carcinoma that is, to the best of our knowledge, the first case of a mixed mucus-secreting and oncocytic carcinoma of the thyroid. We also describe the histochemical, immunohistochemical, and ultrastructural features of this tumor. A 59-year-old man complaining of severe bone pain and weight loss underwent clinical and radiologic investigations. The studies revealed a nodule in the left thyroid lobe that was "cold" by (131)I scintiscan and multiple lytic lesions of the skeleton that showed increased uptake by (99m)Tc-Sestamibi scintiscan. Left hemithyroidectomy was performed and the surgical specimen contained a well-circumscribed nodule of 3 cm in the greatest diameter. Light microscopy showed an oncocytic carcinoma with an area of glandular and papillary proliferation of mucin-producing cells. A double histochemical approach (Alcian blue-periodic acid-Schiff and Alcian blue-high-iron diamine) combined with ultrastructural investigation confirmed the presence of true mucus, ruling out the presence of breakdown products of thyroglobulin. Ultrastructural and immunohistochemical studies, together with clinical findings, excluded a possible metastatic origin of the mucin-producing component.

Adenocarcinoma, Mucinous↗

PubMed2000

Mixed endocrine-exocrine tumors of the gastrointestinal tract.

Mixed endocrine-exocrine tumors of the gastrointestinal tract are rare neoplasms, which have been reported in the literature mainly as case reports and have been designated with a various and rather confusing terminology. In this review, on the basis of personally studied cases and of the analysis of cases reported in the literature, we have tried to identify types of mixed endocrine-exocrine tumors showing different clinicopathologic and biological characteristics. We have also tried to group the different clinicopathologic entities in prognostic classes which include: benign, low-grade, intermediate grade, and high-grade malignant mixed endocrine-exocrine tumors. The criteria for identifying the various types of mixed endocrine-exocrine tumors are extensively discussed.

Adenocarcinoma↗

PubMed1999

Immunohistochemical localization of alpha- and betaA-subunits of inhibin/activin in human normal endocrine cells and related tumors of the digestive system.

Activin A and inhibin A, first isolated from the ovary, are dimeric proteins able to modulate pituitary FSH secretion. Inhibin A is a heterodimer composed of one alpha-subunit and one betaA-subunit (alpha-betaA), while activin A is a homodimer of the betaA-subunit (betaA-betaA). Their identification in several tissues has suggested that they have numerous physiological functions, acting as either paracrine or autocrine factors. The aim of this study was to evaluate the expression of activin A and inhibin A in normal endocrine cells and in 70 endocrine tumours from different sites in the gastro-entero-pancreatic system, using specific monoclonal antibodies directed against the alpha- and betaA-subunits of inhibin/activin. Immunoreactivity for the betaA-subunit, but not for the alpha-subunit, was observed in normal G, EC, and GIP cells of the antrum and duodenum, and in pancreatic A cells. BetaA-subunit expression was observed in G cell and A cell tumours, and in a few insulinomas and ileal EC cell carcinoids. The alpha-subunit was found in rare cells in 7 of the 70 tumours and was colocalized with the betaA-subunit in only 1 tumor. Specific types of endocrine cells from the gut and pancreas appear to produce only activin A, a possible paracrine or autocrine modulator. Activin A is mainly produced by tumours derived from endocrine cells that normally express it.

Activins↗

PubMed1999

ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: prognostic evaluation by pathological analysis.

BACKGROUND & AIMS: Gastric endocrine tumors show a wide spectrum of clinical behavior, and prognostic assessement of individual tumors is difficult. The aims of this work were to identify predictors of tumor malignancy and patient outcome and to provide a rationale for treatment guidelines. METHODS: Gastric endocrine tumors (86 enterochromaffin-like cell carcinoids and 16 poorly differentiated carcinomas) were investigated for 15 clinicopathologic variables and for expression of Ki67, P53, and BCL-2 proteins. Data were analyzed by univariate and multivariate statistics for evidence of tumor malignancy and patient survival. RESULTS: Histological grades 2 and 3, size >/=3 cm, 9 or more mitoses, or >/=300 Ki67-positive cells per 10 high-power fields identified 26 of 33 (79%) malignant (metastatic or deeply invasive) tumors, and size <1 cm and/or growth restricted to the mucosa characterized 46 of 69 (67%) tumors with benign behavior during a median follow-up of 39 months. Malignancy-predictive models were developed using angioinvasion, size, clinicopathologic type, mitotic index, and Ki67 index. The same variables, in addition to deep gastric wall invasion and histological grade, predicted patient outcome. CONCLUSIONS: Criteria for the assessment of malignancy risk and patient outcome were developed for the different tumors, providing a basis for treatment guidelines.

Analysis of Variance↗

PubMed1999

Clinicopathological profile as a basis for classification of the endocrine tumours of the gastroenteropancreatic tract.

Recent developments in the field of endocrine cell biology and pathology, at both morphologic and molecular levels, are briefly outlined and discussed as a basis for endocrine tumour characterization. The main clinicopathological tools available for the identification and characterization of endocrine tumours are discussed. Based on this, classifications of endocrine tumours of the pancreas and gastrointestinal tract are developed covering most clinical (hyperfunctional syndromes included), pathologic and biological patterns and with special emphasis on tumour prognosis.

Endocrine Gland Neoplasms↗

PubMed1998

Temporary drainage of symptomatic malignant ascites by a catheter inserted under computerized tomography.

The development of malignant ascites is an unfavorable prognostic sign in patients with advanced cancer. Interventions may be justified when discomfort and overall compromise in well-being are due to diaphragmatic spinting and abdominal compression of viscera. A patient with symptomatic ascites was admitted to hospital for temporary drainage using a catheter inserted under computerized tomography. Over 12 liters of fluids were removed in 3 days, without complications. A minimal ascitic leakage occurred after removing the cannula. Dyspnea and gastrointestinal symptoms improved and the patient died with good symptom control 15 days later. This approach should be considered in advanced cancer patients with symptomatic ascites that is not responsive to diuretics.

Aged↗

PubMed1998

Primary care management of otitis externa.

Otitis externa (OE) is an acute, painful inflammatory condition of the external auditory canal that affects all age groups and accounts for about half of all patients presenting with ear pain. Common causes are gram-negative bacteria, Staphylococcus aureus, fungi, and dermatologic conditions such as eczema, seborrhea, and psoriasis. Risk increases with prolonged exposure to heat and moisture, especially in those who swim frequently or live in a tropical climate. Treatment involves cleaning the canal thoroughly and instilling ototopical broad-spectrum antibiotics. Although OE is relatively benign and easy to treat in the primary care setting, it can have life-threatening complications, especially in diabetic and immunocompromised patients. This article reviews the differential diagnosis, outlines treatment, and discusses preventive measures. A patient-education sheet is provided.

Diagnosis, Differential↗

PubMed1998

High expression of growth factors and growth factor receptors in ovarian metastases from ileal carcinoids: an immunohistochemical study of 2 cases.

OBJECTIVE AND DESIGN: Ovarian metastatic carcinoids are rare neoplasms that show prominent fibrosis of tumor stroma and are often associated with peritoneal carcinomatosis. We studied formalin-fixed and paraffin-embedded tumor specimens of 2 cases of ovarian metastases from ileal enterochromaffin cell carcinoids immunohistochemically to evaluate whether acidic fibroblast growth factor (aFGF), transforming growth factor-alpha (TGFalpha), and their respective receptors (fibroblast growth factor receptor-4 [FGFR4] and epidermal growth factor receptor [EGFR]) may play a role in the pathogenesis of stromal fibroblast reaction and in the mechanism of tumor dissemination. RESULTS: In both cases, the majority of tumor cells expressed immunoreactivity for aFGF, FGFR4, and TGFalpha. Immunoreactivity for FGFR4 was detected in stromal cells of both cases, while EGFR-positive stromal cells were found in only 1 case. Immunoreactivity for FGFR4 was also found in peritoneal mesothelial cells. CONCLUSIONS: The coexpression of aFGF and FGFR4 in neoplastic enterochromaffin cells suggests that aFGF may act as an autocrine factor stimulating tumor cell growth. In addition, aFGF and TGFalpha may stimulate, in a paracrine fashion, the proliferation of FGFR4- and EGFR-immunoreactive stromal fibroblasts. Finally, interaction of aFGF-immunoreactive enterochromaffin cells with FGFR4-bearing mesothelial cells may play a role in the mechanism of serosal implant and spread of tumor cells.

Aged↗

PubMed1997

Immunohistochemical localization of acidic fibroblast growth factor in normal human enterochromaffin cells and related gastrointestinal tumours.

Acidic fibroblast growth factor (aFGF) is a member of the structurally related heparin-binding growth factor family. The best studied members of this family are aFGF and basic FGF (bFGF), which are potent mitogens and differentiation factors for mesoderm-derived cells, including fibroblasts. This study was designed to verify the immunohistochemical expression of aFGF in normal human endocrine cells of the gut and in related endocrine tumours. We examined normal gastrointestinal mucosa from seven different subjects and 41 gut endocrine tumours from different sites, including stomach, duodenum, and small and large intestine, using an aFGF polyclonal antibody with no cross-reactivity for bFGF. We localized aFGF in a fraction of serotonin-producing enterochromaffin (EC) cells of the normal gut, while it was absent in gastrin (G), CCK, secretion (S), somatostatin (D) and glicentin (L) cells. aFGF immunoreactivity was also expressed in serotonin producing EC cell tumours, but not in other functional types of gut endocrine neoplasms investigated, including gastric ECL cell, duodenal somatostatin and gastrin cell, and rectal L cell tumours. A positive correlation was found between expression of aFGF and the amount of tumour fibrous stroma, suggesting that aFGF may be involved in proliferation and activity of stromal fibroblasts.

Adolescent↗

PubMed1997

Uptake of In-111 pentetreotide by normally functioning nodular goiters.

After the intravenous administration of a radiolabeled somatostatin analogue (octreotide), normal thyroid and neoplastic and nonneoplastic thyroid lesions can be visualized. The authors present the cases of two patients who underwent somatostatin receptor scintigraphy (SSRS) using In-111 pentetreotide: one for the study of suspected paraneoplastic ACTH hypersecretion, and the other for a restaging of breast carcinoma with neuroendocrine features. In both patients, SSRS revealed increased uptake in the thyroid, corresponding to "cold" nodules on Tc-99m pertechnetate imaging. Cytologic and histologic examinations showed the typical features of thyroid goiters without lymphocytic infiltration.

Adenoma↗

PubMed1996

Prognostic criteria in nonfunctioning pancreatic endocrine tumours.

To identify prognostic subgroups among non-functioning (nonsyndromic) pancreatic endocrine tumours, a series of 61 tumours were analysed systematically for macroscopic, histopathological and immunohistochemical variables potentially predictive of malignancy. High-grade nuclear atypia, elevated mitotic rate and multifocal necrosis allowed us to separate 5 poorly differentiated carcinomas from 56 well differentiated tumours. Among the latter, 29 well-differentiated carcinomas showing gross local invasion or metastases were identified. Vascular or perineural microinvasion, Ki67 proliferative index > 2%, mitotic rate > or = 2, size > or = 4 cm, capsular penetration, nuclear atypia, lack of progesterone receptors and presence of calcitonin were among the variables correlated with malignancy. The first two were the most sensitive and specific. Their presence or absence was used in the 27 tumours lacking evidence of malignancy at the time of surgery to separate 11 cases with increased risk of malignancy (in 2 of which metastases developed during follow-up) from 16 cases with limited risk. The resulting four prognostic groups of non-functioning pancreatic endocrine tumours (limited- and increased-risk tumours, well-differentiated carcinomas and poorly differentiated carcinomas) showed distinct survival curves, which were significantly affected by vascular microinvasion, Ki67 proliferative index and metastases.

Adult↗

PubMed1996

Gastric carcinoids and neuroendocrine carcinomas: pathogenesis, pathology, and behavior.

The goal of this study was to provide information of prognostic value for gastric endocrine tumors. A total of 205 gastric endocrine tumors have been studied: 193 well differentiated tumors [2 gastrin cell tumors, 191 enterochromaffin-like (ECL) cell tumors] and 12 poorly differentiated carcinomas. Subtyping of ECL cell tumors (carcinoids) resulted in 152 associated with chronic atrophic gastritis (CAG) (type 1); 12 associated with hypertrophic gastropathy (HG) due to Zollinger-Ellison syndrome with multiple endocrine neoplasia type I (type 2), and 27 with no specific association (type 3, sporadic). Type 1 cases occurred most often in female (108 of 152), elderly (mean 63 years) patients, with no tumor-related death at an overall mean follow-up of 53 months. The 12 type 2 cases were equally distributed between the sexes (six of each), with a mean age of 45 years; there was one tumor-related death (49 months after diagnosis) and an overall mean survival of 84 months. Type 3 cases were mostly in men (20 of 27), with a mean age of 55 years; there were seven tumor-related deaths at a mean follow-up of 28 months. Poorly differentiated neuroendocrine carcinomas were observed in elderly patients (mean 63 years, range 41-76 years) of both sexes, with nine tumor-related deaths and a mean survival of 7 months. It was concluded that correct clinicopathologic subtyping may predict the clinical behavior of gastric endocrine tumors.

Adult↗

PubMed1995

Pituitary lesions in multiple endocrine neoplasia syndrome (MENS) type 1.

This review summarizes knowledge on pathology of proliferative lesions of the pituitary gland in multiple endocrine neoplasia syndrome type 1 (MENS 1). When compared with sporadic tumors occurring in general population, pituitary adenomas associated with MENS 1 show the following distinguishing features: (1) they are more often endocrinologically functional, (2) they are more often GH or PRL-producing and (3) they are more frequently plurihormonal. The study of autoptic cases discloses that pituitary PRL or mixed GH-PRL cell adenomas in MENS are multiple and are associated with PRL or GH cell hyperplasia of the peritumoral parenchyma.

Adenoma↗