Biomedical subjects

Paolo Viacava

Publications and source records attributed to Paolo Viacava.

At least 19 recordsLinked to original sources

PubMed2006

ClC-5 does not affect megalin expression and function in the thyroid.

Megalin is an endocytic receptor responsible for thyroglobulin (Tg) transcytosis, a process that favors hormone release. Accordingly, megalin KO mice have primary hypothyroidism. In the kidney, megalin expression is reduced when the gene encoding the chloride transporter ClC-5 is mutated. We investigated whether megalin expression and function in the thyroid are affected by ClC-5 using a ClC-5 KO mouse model. By Western blotting, ClC-5 was found in thyroid tissue extracts of WT, but not of ClC-5 KO mice. In addition, ClC-5 was found to be expressed by cultured thyroid cells (FRTL-5). The thyroid size, weight, and histology were similar in ClC- 5 KO and WT mice, as were the amounts of megalin in thyroid extracts. Accordingly, serum Tg, a measure of megalin-mediated transcytosis, was similar in WT and ClC-5 KO mice, suggesting that megalin function was unaffected. Thus, unlike in megalin KO mice, in ClC-5 KO mice thyroid function was unchanged, as indicated by the normal serum FT4 and TSH. We concluded that in the thyroid, unlike in the kidney, ClC-5 does not affect megalin expression and function, suggesting that megalin is differentially regulated in these two organs.

Animals↗

PubMed2006

Genetic analyses in familial isolated hyperparathyroidism: implication for clinical assessment and surgical management.

OBJECTIVE: Familial isolated primary hyperparathyroidism (FIPH) can result from either incomplete expression of a syndromic form of familial primary hyperparathyroidism [multiple endocrine neoplasia type 1 (MEN 1), hyperparathyroidism-jaw tumour syndrome (HPT-JT) or familial hypocalciuric hypercalcaemia (FHH)] or still unrecognized causes. Design Genetic analyses of MEN1, HRPT2 and CASR genes in FIHP. PATIENTS: Seven well-characterized Italian kindreds with FIHP, with negative clinical features for MEN 1, HPT-JT and FHH. The mean age (+/- SD) at diagnosis was 45 +/- 17 years (range 18-70 years) in the probands and 42 +/- 18 years (range 15-69 years) in the other affected subjects. MEASUREMENTS: Direct sequencing of germline DNA of the MEN1, HRPT2 and CASR genes from probands. The region of interest was amplified in some family members. RESULTS: Germline MEN1 mutations were detected in three kindreds. Multiglandular involvement was found in all but one affected subject belonging to the three kindreds with MEN1 mutations. In these patients persistence/relapse of the disease was observed unless an extensive parathyroidectomy (excision of 3(1)/(2) glands) had been performed, with the exception of one patient, who is currently normocalcaemic 168 months after excision of two glands. No mutations of MEN1, HRPT2 and CASR genes were identified in the remaining four families. CONCLUSIONS: MEN1 genotyping appears worthwhile in FIHP families, as the finding of mutation(s) may predict multiglandular involvement and therefore have practical surgical implications, and prompt further investigation in the family, with the possibility of identifying new cases and beginning a programme of periodic surveillance for emergence of tumours in all carriers.

Adenoma↗

PubMed2006

Microvessel density in human normal and neoplastic parathyroids.

Objective. Information on angiogenesis in parathyroid pathology is scanty and in particular no data are available in parathyroid carcinomas. The aim of this study was to analyze angiogenesis as microvascular density (MVD) in parathyroid neoplastic progression from normal gland to adenoma and carcinoma. Methods. Sections from formalin-fixed, paraffin-embedded specimens of 33 normal parathyroids, 43 sporadic parathyroid adenomas, and 6 parathyroid carcinomas were cut for immunohistochemistry using anti-endothelial marker CD34. MVD was evaluated in each specimen as number microvessels per mm2. MVD data were compared with some anatomoclinical parameters as tumor size, serum calcium, and parathyroid hormone (PTH) level. Results. All normal parathyroid glands, all carcinomas, and 8 adenomas out of 43 (18%) showed MVD less than 100 microvessels/mm2 (median 70.8; 95%CI 66.9-88.5); in the majority of parathyroid adenomas (n = 35; 82%) the number of microvessels/mm2 was higher than 100 (median 188.3; 95%CI 174.9-210.1). In adenomas both preoperative serum intact PTH concentration and the diameters were significantly and inversely related to the microvessel density (r = 0.320, p < 0.05 and r = 0.334, p < 0.05, respectively). Conclusions. This study shows that in parathyroid adenomas MVD is heterogeneous and negatively related to the endocrine activity (secretory status and tumor size). Therefore, angiogenesis in parathyroid adenomas and carcinomas appears to be an early event, which does not follow a parallel increase in size.

Adenoma↗

PubMed2006

Microvessel density and vascular endothelial growth factor (VEGF) expression in human radicular cysts.

PURPOSE: To assess vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) by immunohistochemistry and to relate them to the inflammatory status in a sample of radicular cysts. METHODS: Specimens of 24 human radicular cysts were examined by immunohistochemistry using antibodies anti-VEGF and anti-CD34 and to evaluate vascular density. Integrity of the epithelium and inflammatory state of the connective tissues were evaluated and related with the immunohistochemical findings. A Spearman correlation test was utilized to compare the means of each parameter. RESULTS: VEGF immunoreactivity was detected in both epithelial and connective tissues of radicular cysts. Stromal cells showed higher levels of VEGF expression when compared to epithelial cells. MVD proved to be related to VEGF expression levels (P < or = 0.01). In addition, increased MVD was associated with high levels of inflammation (P < or = 0.01). Most of the specimens showed a massive inflammatory infiltrate in the connective tissue. The integrity of the cystic lining tend to decrease with increased inflammation.

Antigens, CD34↗

PubMed2005

Feline cutaneous and visceral necrotizing panniculitis and steatitis associated with a pancreatic tumour.

The association of pancreatic disorders with fat necrosis in domestic animals is rare. This report concerns a case of cutaneous/subcutaneous necrotizing panniculitis and steatitis associated with a pancreatic adenocarcinoma in an 11-year-old male Siamese cat. Clinical investigation revealed variably sized nodules on the trunk, limbs and abdomen. Some of them were ulcerated; others showed a shiny yellow necrotic background featuring irregular sinus tracts. The cat was euthanized at the owner's request before a diagnosis could be made. At necropsy, abundant oily material resembling mustard replaced the subcutaneous tissue and small yellow nodules were disseminated in the omentum, mesentery and serosa of the abdomen. A multilobulated mass arising from the anterior pancreatic head was found along with liver and lymph node metastasis. Histopathology showed wide fistulous tracts draining necrotic fat from the subcutis toward the surface and multifocal areas of necrotic adipocytes replacing the panniculus. Duct-like structures and tubules lined by neoplastic epithelial cells were observed in the primary pancreatic tumour and in the metastatic sites. The aetiology of the fat necrosis was possibly the result of systemic release of lipolytic pancreatic enzymes.

Adenocarcinoma↗

PubMed2004

Severe aortic stenosis and myocardial function: diagnostic and prognostic usefulness of ultrasonic integrated backscatter analysis.

BACKGROUND: The aim of this study was to assess the myocardial reflectivity pattern in severe aortic valve stenosis through the use of integrated backscatter (IBS) analysis. Patients with aortic stenosis (AS) were carefully selected in the Department of Cardiology. METHODS AND RESULTS: Thirty-five subjects (AS: valve orifice < or =1 cm2; 12 female; mean age, 71.8+/-6.2 years) and 25 healthy subjects were studied. All subjects of the study had conventional 2D-Doppler echocardiography and IBS. Backscatter signal was sampled at the septum and posterior wall levels. Patients with AS were divided into 2 groups: 16 patients with initial signs of congestive heart failure and a depressed left ventricular systolic function (DSF) (ejection fraction [EF] range, 35% to 50%) and 19 asymptomatic patients with normal left ventricular systolic function (NSF) (EF >50%). Myocardial echo intensity (pericardium related) was significantly higher at the septum and posterior wall levels in DSF than in NSF and in control subjects. IBS variation, as an expression of variation of the signal, appeared to be significantly lower in AS with DSF than in NSF and in control subjects, at both the septum and posterior wall levels. Patients with DSF underwent aortic valve replacement, and, during surgical intervention, a septal myocardial biopsy was made for evaluation of myocardium/fibrosis ratio. Abnormally increased echo intensity was detected in left ventricular pressure overload by severe aortic stenosis and correlated with increase of myocardial collagen content (operating biopsy). CONCLUSIONS: One year after aortic valve replacement, we observed a significant reduction of left ventricular mass, and, only if pericardial indexed IBS value (reduction of interstitial fibrosis) decreased, it was possible to observe an improvement of EF and of IBS variation.

Aged↗

PubMed2004

Angiogenesis and VEGF expression in pre-invasive lesions of the human breast.

Angiogenesis (as microvascular density-MVD) and vascular endothelial growth factor (VEGF) expression were evaluated by immunohistochemistry in all types of human pre-invasive breast lesion, un-associated with invasive carcinoma, including florid ductal hyperplasia of usual type (FDHUT, 40 cases), atypical ductal hyperplasia (ADH, 10), well-differentiated intraductal carcinoma (WDIC, 16), intermediately differentiated intraductal carcinoma (IDIC, 25), poorly differentiated intraductal carcinoma (PDIC, 20), atypical lobular hyperplasia (ALH, 13), and lobular carcinoma in situ (LCIS, 12). Both parameters were also studied in normal glandular structures obtained from normal breasts or from breasts containing pre-invasive lesions. Increased vascularization was present in all lesion types (MVD mean values (expressed as vessel number/mm(2)): 115 +/- 8 in normal lobules, 146 +/- 26 in lesions; p < 0.05) and increased with lesion severity. In ductal lesions, MVDs were significantly higher in PDIC (190 +/- 65) and IDIC (167 +/- 61) than in FDHUT (123 +/- 40) and ADH (122 +/- 47); MVD was much higher in PDIC than in WDIC (p < 0.001). WDIC showed peculiar features, with a degree of vascularization closer to hyperplasia than to the other histological types of in situ ductal cancer; this observation is in line with the hypothesis that IDIC and PDIC may originate 'de novo', without a mandatory transition through WDIC. LCIS was more vascularized than ALH (168 +/- 50 and 125 +/- 40, respectively; p < 0.05), showing MVD values similar to those of PDIC and IDIC. The vascularization of normal lobules was constant, regardless of their association with lesions. VEGF expression in normal glandular structures was lower than in lesions, with the highest levels found in ductal lesions when compared with lobular lesions. No correlation was found between VEGF expression and the degree and/or type of vascularization.

Adult↗

PubMed2004

Clinicopathological significance of GADD45 gene alterations in human familial breast carcinoma.

GADD45 is a DNA damage responsive gene, induced following BRCA1 expression. Mutations at GADD45 might substitute for p53 alterations in hereditary breast tumours characterized by wild-type p53. We analyzed GADD45 alterations in 59 (15 BRCA-associated) familial breast carcinomas. No mutations were found. LOH at GADD45 locus was identified in 19/59 tumours. GADD45 does not appear to be a frequent mutational target in hereditary breast cancer.

Breast Neoplasms↗

PubMed2004

A reappraisal of the Rb1 gene abnormalities in the diagnosis of parathyroid cancer.

OBJECTIVES: Some histological features may suggest the malignant nature of a parathyroid tumour. However, the diagnosis of parathyroid cancer can only be definitively established in the presence of local invasion or metastases. DESIGN: We further investigated the role of the retinoblastoma gene (Rb1) and the breast cancer susceptibility gene (BRCA2) in the differential diagnosis between benign and malignant parathyroid tumours by evaluating loss of heterozygosity (LOH) at these loci and Rb protein (pRb) immunohistochemistry. PATIENTS AND MEASUREMENTS: Fifty-three parathyroid adenomas from patients with sporadic primary hyperparathyroidism (PHPT) and 10 parathyroid cancer specimens were studied. Microsatellite polymorphisms at the Rb1 and BRCA2 loci were polymerase chain reaction (PCR) amplified from each patient's paired tumour and leucocyte DNA samples, using oligonucleotide primers flanking the repeat sequence. Immunohistochemical staining of pRb was carried out using a monoclonal antibody. RESULTS: All but one of the 53 tumour-leucocyte pairs was informative for at least one of the three polymorphic markers of the Rb1 gene. Fifteen adenomas (28.8%) showed LOH. Regarding the BRCA2 gene, 46 tumour-leucocyte pairs were informative and LOH was present in eight (17.4%). All six carcinomas had LOH for at least one marker at the Rb1 locus. LOH for the BRCA2 microsatellite was found in three of the five informative primary tumour samples. Immunohistochemical analysis revealed that all adenomas were positive and the number of pRb-positive cells varied significantly among different samples. The mean percentage of stained cells was 15.7%. Eleven of the 30 (36.7%) adenomas showed sparse positive staining, 13 (43.3%) intermediate staining and six (20%) extensive staining. All parathyroid cancers were entirely negative for pRb immunostaining. CONCLUSIONS: Inactivation of the Rb1 gene is a common event in parathyroid tumorigenesis. Retention of heterozygosity seems to exclude parathyroid malignancy, which is suggested by the combined finding of LOH and lack of protein expression.

Adenoma↗

PubMed2004

The sodium-iodide symporter protein is always present at a low expression and confined to the cell membrane in nonfunctioning nonadenomatous nodules of toxic nodular goitre.

OBJECTIVE: The sodium-iodide (Na(+)/I(-)) symporter (NIS) is known to be overexpressed in toxic adenomas and in about half of benign solitary nonfunctioning adenomas of the thyroid. In nonfunctioning adenomas, however, the protein is localized mainly in the cytoplasm and fails to reach the basolateral membrane of the follicular cell where it is found in normal thyroid tissue and in hyperfunctioning adenomas. Our aim was to study both the level of expression and the cell localization of NIS in nonfunctioning nonadenomatous nodules of toxic nodular goitre. DESIGN AND PATIENTS: Tissue specimens from nine patients who were submitted to surgery for toxic or functionally autonomous goitre were studied. Tissues from 12 patients who underwent lobectomy for a toxic thyroid adenoma were used as controls. MEASUREMENTS: Tissue sections embedded in paraffin were stained with haematoxylin-eosin for histological evaluation and for immunohistochemistry using a monoclonal antibody that recognized human (h) NIS. RESULTS: Functioning and nonfunctioning nodules scattered in multinodular goitres consisted of unencapsulated micro/macrofollicular aggregates. All toxic adenomas were characterized by a micro/macrofollicular pattern of growth and histological examination showed that they were surrounded by a capsule. Like the 12 toxic adenomas, all the 14 functioning hyperplastic nodules and two adenomas of toxic multinodular goitre showed a high level of hNIS protein expression with respect to the normal collateral parenchyma and, in all cases, the protein was confined to the cell membrane. CONCLUSIONS: Contrary to what was observed for solitary nonfunctioning thyroid adenomas, all the 19 nonfunctioning hyperplastic nodules showed a very low hNIS and this was always confined to the cell membrane. These data suggest that the mechanisms leading to loss of iodide uptake in nonfunctioning hyperplastic nodules of toxic multinodular goitre are different from those that act on solitary nonfunctioning follicular adenomas.

Adult↗

PubMed2004

Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors.

We investigated the involvement of the HRPT2 gene by loss of heterozygosity analysis and direct sequencing in a kindred with hyperparathyroidism-jaw tumor syndrome (HPT-JT) and three kindreds with familial isolated primary hyperparathyroidism (FIHP). Seven patients with sporadic parathyroid cancers and 35 with parathyroid adenomas with no family history of primary hyperparathyroidism or HPT-JT were also studied. A germline heterozygous substitution G to A was found in the donor splice site of intron 1 in one of the three FIHP families. No mutations were identified in the HPT-JT kindred. A somatic HRPT2 mutation was found in four of seven patients with parathyroid cancers, two of which were unreported frameshift mutations (195insT and 195insA) in exon 2. Consistent with recent findings, two of seven patients with sporadic parathyroid cancer had germline mutations. Four adenomas showed loss of heterozygosity at HRPT2, whereas a somatic HRPT2 mutation was found in one. In conclusion, we provide additional evidence for a strong association between HRPT2 gene mutations and sporadic parathyroid cancer. The finding that two of the seven patients with sporadic parathyroid cancer carried an HRPT2 germline mutation suggests that they might have occult HPT-JT. Our results also confirm the need for testing HRPT2 gene in FIHP families.

Adenoma↗

PubMed2004

PPARgamma inhibits GH synthesis and secretion and increases apoptosis of pituitary GH-secreting adenomas.

OBJECTIVE: The objective of the study was to evaluate the expression and functional activity of Peroxisome proliferator-activated receptor (PPAR) gamma in pituitary adenomas from 14 consecutive acromegalic patients and to establish its role in apoptosis. SUBJECTS AND METHODS: Fourteen consecutive acromegalic patients were enrolled in the study. Wistar-Furth rats were used for in vivo studies. Expression of PPARgamma was evaluated by RT-PCR and Western blot. Apoptosis and cell cycle were assessed by FACS analysis. The effects of PPARgamma ligands on transcriptional regulation of GH gene were evaluated by RT-PCR and electromobility shift assay. RESULTS: PPARgamma was expressed in all human GH-secreting adenoma (GH-oma), in normal pituitary tissue samples (39+/-24% and 78+/-5% of immunostained nuclei respectively; P<0.0002; ANOVA), and in rat GH-secreting (GH3) cells. A PPRE-containing reporter plasmid transfected into GH3 cells was activated by ciglitazone or rosiglitazone (TZDs), indicating that PPARgamma was functionally active. Treatment of GH3 cells with TZDs increased apoptosis in a dose-dependent manner (P=0.0003) and arrested cell proliferation, reducing the number of cells in the S-phase (P<0.0001 vs untreated cells). TZDs increased the expression of TRAIL, leaving unaffected that of p53 and Bax. TZDs reduced GH concentrations in the culture media from 43.7+/-5.4 ng/ml to 2.1+/-0.3 ng/ml (P<0.0001) and in cell extracts (P<0.004). PPARgamma-RXRalpha heterodimers bound to GH promoter, inhibiting its activity and reducing GH mRNA levels (1.8 x 10(6) vs 5.7 x 10(6) transcripts respectively vs untreated cells; P<0.002). Subcutaneous GH-oma developed in rats injected with GH3 cells; tumor growth increased in placebo-treated rats and to a lesser extent in TZDs-treated animals (24.1+/-2.0 g, and 14.8+/-4.2 g respectively, P<0.03). Serum GH concentrations were lower in TZDs-treated rats than in controls (871+/-67 ng/ml vs 1.309+/-238 ng/ml; P<0.05). CONCLUSIONS: The results of this study indicate that PPARgamma controls GH transcription and secretion as well as apoptosis and growth of GH-oma; thus, TZDs have the potential of a useful tool in the complex therapeutic management of acromegalic patients.

Adenoma↗

PubMed2004

Left atrial cardiac hemangioma: a report of two cases.

Cardiac hemangiomas are exceptionally rare tumors with an incidence of 1 to 3% of all detected benign heart neoplasms. We report 2 cases of left atrial hemangioma of which only one associated with clinical symptoms such as dyspnea and palpitations. Two years following surgical excision of the tumors, there was no echocardiographic evidence of recurrence.

Aged↗

PubMed2003

Detection of RASSF1A aberrant promoter hypermethylation in sputum from chronic smokers and ductal carcinoma in situ from breast cancer patients.

The newly identified 3p21.3 tumour suppressor gene RASSF1A is methylated in the majority of primary lung tumours, lung tumour cell lines and in a variable percentage of breast tumours. To determine the extent of RASSF1A promoter hypermethylation in early lung tumorigenesis, we analysed sputum samples from lung cancer patients and from current and former smokers using a sensitive methylation-specific PCR (MSP) technique. We also analysed RASSF1A promoter region hypermethylation in trios of normal breast/invasive ductal breast carcinoma/ductal carcinoma in situ (DCIS) from breast cancer patients and DCIS without invasive cancer. We found that 50% of small cell lung cancer (SCLC) and 21% of non-small cell lung cancer (NSCLC) patients had RASSF1A methylation, while one of two former smokers and four of 13 current smokers demonstrated RASSF1A methylation in sputum. Furthermore, two of the four current smokers and one former smoker showing RASSF1A methylation in their sputum developed cancer within 12-14 months of bronchoscopy. In our breast cancer trios, RASSF1A promoter hypermethylation was detected in 65% of invasive cancers, in 42% of corresponding DCIS but in none of the normal breast samples. In addition, we found that three out of 10 DCIS without invasive breast cancer also underwent RASSF1A promoter hypermethylation. Our findings suggest that RASSF1A promoter region hypermethylation may be a useful molecular marker for early detection of lung cancer. Furthermore, since RASSF1A promoter hypermethylation was detected in ductal carcinoma in situ, inactivation of RASSF1A may be an early event in breast tumorigenesis.

Base Sequence↗

PubMed2003

p53 inactivation is a rare event in familial breast tumors negative for BRCA1 and BRCA2 mutations.

Germline mutations at BRCA1 or BRCA2 genes result in susceptibility to breast and ovarian cancers. BRCA1- and BRCA2-associated tumors have distinct histologic and molecular phenotypes, as compared to sporadic breast tumors. Typically, a higher grade of malignancy is observed in BRCA-associated cancers. A number of studies have suggested that BRCA1 and BRCA2 proteins are of importance in DNA repair and maintenance of genome integrity, bringing about molecular models of tumor pathogenesis. In particular, alterations at p53 gene have been suggested to be a necessary step in the tumorigenesis of BRCA-associated carcinomas. In fact, BRCA-associated breast cancers have higher p53 mutation frequencies than sporadic ones. At present, very little is known regarding BRCA non-associated familial tumors (termed BRCAx tumors). To our knowledge no data is available on p53 alterations in this sub-group of familial tumors. In this study p53 alteration frequencies were evaluated in 13 BRCA1, 11 BRCA2 and 55 BRCAx breast tumors. Tumor samples were analyzed for p53 gene mutations by PCR-SSCP/direct sequencing, and for p53 protein overexpression by immunohistochemistry (IHC). Altogether, p53 alterations were detected in 54% of BRCAI tumors compared with 5% of BRCAx tumors. No p53 alteration was found in BRCA2 tumors. While loss of p53 checkpoint control is likely to be an important step in the molecular pathogenesis of BRCA1-associated cancers, our data seem to indicate a p53-independent molecular mechanism underlying BRCAx neoplastic transformation.

Adult↗

PubMed2003

Congenital hypothyroidism due to a new deletion in the sodium/iodide symporter protein.

OBJECTIVE: Iodide transport defect (ITD) is a rare disorder characterised by an inability of the thyroid to maintain an iodide gradient across the basolateral membrane of thyroid follicular cells, that often results in congenital hypothyroidism. When present the defect is also found in the salivary glands and gastric mucosa and it has been shown to arise from abnormalities of the sodium/iodide symporter (NIS). PATIENT: We describe a woman with hypothyroidism identified at the 3rd month of life. The diagnosis of ITD was suspected because of nodular goitre, and little if any iodide uptake by the thyroid and salivary glands. Treatment with iodide partially corrected the hypothyroidism; however, long-term substitution therapy with L-thyroxine was started. MEASUREMENTS: Thyroid radioiodide uptake was only 1.4% and 0.3% at 1 and 24 h after the administration of recombinant human TSH. The saliva to plasma I- ratio was 1.1 indicating that the inability of the thyroid gland to concentrate I- was also present in the salivary glands. RESULTS: Analysis of the patient's NIS gene revealed a 15 nucleotide (nt) deletion of the coding sequence (nt 1314 through nt 1328) and the insertion of 15 nt duplicating the first 15 nt of the adjacent intron. The patient was homozygous for this insertion/deletion, while both consanguineous parents were heterozygous. This deletion predicts the production of a protein lacking the five terminal amino acids of exon XI (439-443) which are located in the 6th intracellular loop. COS-7 cells transfected with a vector expressing the mutant del-(439-443) NIS failed to concentrate iodide, suggesting that the mutation was the direct cause of the ITD in this patient. CONCLUSION: In conclusion we describe the first Italian case of congenital hypothyroidism due to a new deletion in the NIS gene.

Adult↗

PubMed2003

Definition of the microvascular pattern of the normal human adult mammary gland.

The present report provides a detailed description of microvascularization in the normal human mammary gland, and defines two novel morphometric parameters to be used as a reference when angiogenesis in breast carcinoma is evaluated. Microvascularization was analysed by histology, immunohistochemistry and computer-assisted analysis in a set of breast tissue samples taken from nine women, during the pre-ovulatory phase of the menstrual cycle. The two parameters designed for image analysis were: vascular density (VD): [microvessel number/(microvessel area + residual stromal area)] x 10 000; and vascular area ratio (VAR): [microvessel area/(microvessel area + residual stromal area)]. In the lobules VD (mean value +/- SE 2.48 +/- 0.14) and VAR (0.33 +/- 0.02) showed little variability and correlated significantly (P < 0.05). The areas occupied by microvessels, stroma and acini remained constant in all lobules (21.53 +/- 1.87%, 42.65 +/- 1.35% and 35.14 +/- 1.57%, respectively). Microvascularization of the lobules was of a sinusoidal type, with large S-shaped capillaries. In the ducts VD (2.95 +/- 0.16) and VAR (0.29 +/- 0.03) showed little variability but did not correlate significantly. Microvascularization of the ducts was of a classic type, with capillaries normal in size and shape. The expression of oestrogen (ER) and progesterone (PR) receptors was analysed by immunohistochemistry and compared with the morphometric results. ER expression levels were in the range 20-25% (24.3 +/- 2.1) and 14-18% (15.4 +/- 1.5) in lobules and ducts, respectively. PR expression levels were in the range 10-13% (11.1 +/- 1.6) and 14-17% (15.2 +/- 1.4), respectively. No correlation was found between ER/PR expression and vascularization parameters.

Adolescent↗

PubMed2003

Changes in the expression of the peroxisome proliferator-activated receptor gamma gene in the colonic polyps and colonic mucosa of acromegalic patients.

Acromegalic patients have an increased prevalence of colonic neoplasms and lower peroxisome proliferator-activated receptor gamma (PPARgamma) levels, the latter acting as a tumor suppressor gene. In this study we evaluated the expression of PPARgamma in the biopsy samples of the polyps and outside polyps colonic mucosa from seven patients with active, untreated acromegaly, 11 with cured disease, and 15 controls. Serum GH and IGF-I levels were higher in patients with untreated acromegaly than in those with acromegaly in remission or controls (P = 0.003 and P = 0.002, respectively) The expression of PPARgamma mRNA (mean +/- SE) was 1) mucosa outside polyps, 24,188 +/- 3,254 transcripts in the controls, 22,432 +/- 2,006 transcripts in acromegaly in remission, and 1,952 +/- 342 transcripts in untreated acromegaly (P < 0.0001 vs. controls and acromegaly in remission); and 2) polyps mucosa, 1,554 +/- 236 transcripts in the controls, 1,112 +/- 143 in acromegaly in remission, and 1,570 +/- 251 in untreated acromegaly (P = NS among polyps groups and mucosa outside polyps of untreated acromegaly; P < 0.0001 vs. mucosa outside polyps of controls and acromegaly in remission). Eighty-five percent of the cells in the mucosa outside polyps from controls or acromegaly in remission were positive at immunohistochemistry, at variance with 45% of the cells from polyps mucosa from each group and from those of mucosa outside polyps of untreated acromegaly (P = 0.0002). In conclusion, patients with untreated acromegaly have reduced expression of PPARgamma in the mucosa outside polyps, which might be reversed by curing the disease; conversely, patients with acromegaly in remission have the same low levels of expression of PPARgamma in the polyps mucosa as untreated acromegaly or controls, supporting the concept that reduced expression of PPARgamma might be an early event in colonic tumorigenesis.

Acromegaly↗