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Biomedical subjects

G Bussolati

Publications and source records attributed to G Bussolati.

At least 55 records · Page 3Linked to original sources

RET/PTC activation in hyalinizing trabecular tumors of the thyroid.

Hyalinizing trabecular tumor (HTT) of the thyroid is a neoplasm of follicular derivation with a histogenesis that is still the subject of debate. Morphologic affinities between HTT and papillary carcinoma, including nuclear pseudoinclusions and grooves, suggest that these tumors may be of similar origin. The authors investigated the relationship between these two types of tumors by assessing HTT for the presence of rearrangements of the proto-oncogene rearranged during transfection (RET) that, in thyroid tumors, are specific for papillary carcinoma. A series of 14 HTTs, including two cases associated with classic papillary carcinoma, was studied by means of immunohistochemistry and reverse transcription-polymerase chain reaction. Seven follicular adenomas with focal hyalinized trabecular areas served as control cases. Three of the 14 HTT cases under consideration displayed rearrangements of RET generating the RET/papillary thyroid carcinoma type 1 (PTC1) oncogene. In another case, RET expression was detected focally by immunohistochemistry alone. Finally, in one mixed HTT-papillary carcinoma sample, RET/PTC1 expression was detected, but only in the papillary component. None of the control follicular adenomas contained rearrangements of RET/PTC. These findings demonstrate that a comparable percentage (28.6%) of HTTs and papillary carcinomas exhibit the same RET proto-oncogene alterations. Thus, HTT may represent the "hyalinizing trabecular" variant of papillary carcinoma rather than a separate entity.

Adenoma↗

Correlative immunohistochemical and reverse transcriptase polymerase chain reaction analysis of somatostatin receptor type 2 in neuroendocrine tumors of the lung.

Somatostatin receptors type 2 (sst2) have been frequently detected in neuroendocrine tumors and bind somatostatin analogues, such as octreotide, with high affinity. Receptor autoradiography, specific mRNA detection and, more recently, antisst2 polyclonal antibodies are currently employed to reveal sst2. The aim of the present study was to investigate by three different techniques the presence of sst2 in a series of 26 neuroendocrine tumors of the lung in which fresh frozen tissue and paraffin sections were available. It was possible, therefore, to compare, in individual cases, RNA analysis studied by reverse transcriptase polymerase chain reaction (RT-PCR), in situ hybridization (ISH), and immunohistochemistry. A series of 20 nonneuroendocrine lung carcinoma samples served as controls. RT-PCR was positive for sst2 in 22 of 26 samples, including 15 of 15 typical carcinoids, 5 of 6 atypical carcinoids, and 2 of 5 small-cell carcinomas. The sst2 mRNA signal obtained by RT-PCR was strong in the majority (87%) of typical carcinoids and of variable intensity in atypical carcinoids and small-cell carcinomas. A weakly positive signal was observed in 5 of 20 control samples. In immunohistochemistry, two different antibodies (anti-sst2) were employed, including a monoclonal antibody, generated in the Department of Pathology, University of Turin. In the majority of samples a good correlation between sst2 mRNA (as detected by RT-PCR) and sst2 protein expression (as detected by immunohistochemistry) was observed. However, one atypical carcinoid and one small-cell carcinoma had focal immunostaining but no RT-PCR signal. ISH performed in selected samples paralleled the results obtained with the other techniques. A low sst2 expression was associated with high grade neuroendocrine tumors and with aggressive behavior. It is concluded that 1) neuroendocrine tumors of the lung express sst2, and there is a correlation between the mRNA amount and the degree of differentiation; 2) immunohistochemistry and ISH are reliable tools to demonstrate sst2 in these tumors; and 3) sst2 identification in tissue sections may provide information on the diagnostic or therapeutic usefulness of somatostatin analogues in individual patients with neuroendocrine tumors.

Adult↗

What modifies the relation between tumour size and lymph node metastases in T1 breast carcinomas?

AIMS: To evaluate which pathological and clinical parameters modify the relation between tumour size and lymph node metastases in invasive breast carcinomas < 20 mm. METHODS: In a retrospective study, 1075 patients with pT1 invasive breast carcinoma and with known nodal status were analysed. The size of the infiltrating tumour was microscopically evaluated, and the in situ component was not considered. The additional pathological parameters considered were: tumour grade, peritumoral vascular invasion, multicentricity, and angiogenesis. The immunophenotype of the tumour was determined as: the expression of oestrogen (ER) and progesterone (PR) receptors, p53, and c-erbB2. The patients were grouped by age as follows: < 50, 51-70, and > 70 years old. RESULTS: Three hundred and seventy four patients (34.8%) were node positive. Univariate analysis showed that nodal positivity was significantly correlated with large tumour size (> 10 mm), vascular invasion, grade 2-3, multicentricity, and high angiogenesis (> 100 microvessels/x20 high power frame). No significant correlation was found between nodal positivity and ER, PR, p53, or c-erbB2 status. Interestingly, the association with in situ carcinoma was correlated with lower nodal positivity in tumours presenting equally sized infiltrating components. Age was an independent variable and significantly modified the risk of nodal positivity in tumours < 1 cm. In fact, in patients under 51 years of age, the proportion of nodal positivity in pT1a tumours was sevenfold higher than in older patients. In patients from 51 to 70 years old, nodal positivity correlated with tumour size, and multicentricity was an additional risk factor. CONCLUSIONS: These data suggest that, together with tumour size, the presence of in situ carcinoma, and vascular invasion, age is one of the most important predictors of metastatic diffusion in breast carcinomas.

Adult↗

Thyroid carcinomas with mixed follicular and C-cell differentiation patterns.

Divergent endocrine-neuroendocrine differentiation in thyroid carcinoma occurs in mixed medullary-follicular carcinomas (MMFC). Less than 40 cases of MMFC have been reported having highly heterogeneous patterns of growth. Classical medullary carcinoma areas may be intermingled with follicles or papillae or even oxyphilic and solid areas. Calcitonin and thyroglobulin are expressed in different cell populations. Presence of the latter suggests a potential usefulness of radioiodine treatment. The clinical behavior of MMFC does not differ from that of ordinary medullary carcinoma. The histogenesis of MMFC is controversial. The genetic analysis of the 2 neoplastic components showed that they are not derived from a common precursor, but rather display remarkable differences in the genetic profile (RET mutations and allelic losses). In addition, in some cases the follicular component was found to be oligo/polyclonal and therefore possibly hyperplastic rather than neoplastic. The follicular cells may have grown into the medullary carcinoma, after acquiring some molecular defect, being "hostage" of the true neoplastic (medullary) component.

Adenocarcinoma, Follicular↗

Expression of the neuroendocrine phenotype in carcinomas of the breast.

Neuroendocrine (NE) features are detectable in carcinomas of the breast either as scattered cells immunoreactive for NE markers in carcinoma of the usual type (NOS), or as special type of tumors where the vast majority of the cells display NE characteristics. The former type of lesions, whose biological and diagnostic significance is not clear yet, might reproduce the same phenomenon known to occur in carcinomas of the gastrointestinal tract and pancreas. In the present review we focus on the latter type of lesions, a spectrum of breast tumors largely composed of NE cells. These carcinomas, that we consider the "NE differentiated carcinomas of the breast," are here distinguished from "breast carcinomas NOS with NE differentiation." The diagnostic and histogenetic features of the various types of "NE differentiated carcinomas of the breast," their histological and cytological features and the role and value of ancillary diagnostic techniques, are reviewed. Data of the literature are discussed and related to a relatively large personal series. In addition, divergent differentiation in NE carcinomas of the breast, which is a relatively frequent phenomenon of diagnostic interest but of unknown significance (mainly involving mucinous intra- and extracellular production) is discussed.

Biomarkers, Tumor↗

Normal values of reactive oxygen metabolites on the cord-blood of full-term infants with a colorimetric method.

The main end-point of the study was to evaluate the normal values of reactive oxygen metabolites (ROMs) in healthy full-term babies. Secondary end-points were differences between groups related to modality of delivery, Apgar score, birth weight, gestational age and sex. All apparently healthy babies born at our institution between 8 a.m. and 8 p.m. Monday to Friday with gestational age 37-42 weeks, delivered both vaginally or by caesarean section and without foetal distress and perinatal asphyxia. ROMs were evaluated by a colorimetric method (d-ROM test) on cord-blood immediately after birth. The values are reported as arbitrary unit U. Carr. Statistical analysis was performed by t-test and by multiple and stepwise regression analysis. We have analyzed 80 babies with mean birth weight 3301 +/- 446 g. and mean gestational age 39.5 +/- 1.0 weeks. The male:female ratio was 1.56 and the median (range) Apgar score was 9 (7-10) at 1' and 10 (9-10) at 5'. The babies born by vaginal delivery were 37 out of 80 while the remaining 43 were delivered by cesarean section. Because the two groups did not differ for the clinical characteristics they were considered together for the determination of the mean value of ROMs and indicated as "total". The mean value +/- SD of ROMs of the "total" was 115.5 +/- 32.6 U. Carr. Significant differences in the mean value of ROMs were not found related to type of delivery, birth weight, gestational age, and Apgar score at 1' and 5'. Instead the female infants had a significantly lower mean value of ROMs than the male babies (respectively 104.4 +/- 32.2 vs 120.2 +/- 30.6 U. Carr.; p = 0.031). Multiple and stepwise regression analyses both demonstrated that the sex of the neonate is able to independently influence the value of ROMs (respectively p = 0.025 and p = 0.035). The main end-point of the study was to determine the standard reference values for this method in the healthy full-term infant at birth: the values of ROMs we found in the "total" population are lower than those of healthy adults (between 250-300 U. Carr.) and similar to those of adults treated with steroids or antioxidant drugs. The finding that the female sex is able to independently determine lower values of ROMs at birth compared to the male sex, lets speculate that the female infants are less prone to oxidative stress in the first moments of life.

Colorimetry↗

[Mortality and morbidity in extremely premature newborns].

The progress of perinatal medicine greatly reduced neonatal mortality and prognosys of the lowest gestational age (G.A.) newborns is improving continuously. The survival of the newborns with G.A. < 32 weeks doubled from the years 1973-1978 to 1995-99 in the our neonatal intensive therapy (TIN), whereas the incidence of the most serious pathologies of prematurity, which increases with the decreasing of G.A., has not changed in the years. In the surfactant era, Respiratory Distress Syndrome is not the first cause of death and Intra Ventricular Hemorrage and Retinopaty Of Prematurity occur now in the lower stage of severity in comparison with the past. Cortison profilaxys antepartum, delivery with caesarian section and agressive intensive neonatal therapy seem to be the reason of these results.

Gestational Age↗

[Congenital cardiopathy in a data-based population].

Altogether 429.139 consecutive births were surveyed during the eighteen years study period by the Emilia-Romagna Registry. Among these, 2147 newborns with congenital heart defects (CHD) (prevalence 5 per 1000) were detected within the first week of life. There were 1607 isolated CHDs and 540 cases had other associated defects. During the study period an increase in prevalence/rate of CHDs was observed (from 3.1 per 1000 in 1980 to over 7 per 1000 in 1998), particularly isolated CHDs increased from 2.2 to 6 per 1000, while the prevalence rate of CHDs cases with other associated anomalies was constant ranging from 1 to 2 per 1000. The increase of isolated CHDs was due to the increased number of "minor" lesions such as ventricular (VSD) and atrial septal defect. The apparent increase in birth prevalence of CHD mainly results from improved diagnosis due to widespread use of color-doppler ecocardiography. As in other studies, a significant shift in the sex-ratio has been documented: a male predominance in transposition of great arteries, left hypoplastic heart and aortic stenosis (male/female ratio 2.2, 2.3, 4.5 respectively) were found; while VSD had a slight female excess (male/female ratio 0.96). The study confirmed that the majority of the affected parents were mothers. The recurrence risk of a cardiac defect in first degree relatives was 2.3%, while the recurrence risk of isolated conotruncal defects was 3.9%. Out of 47 cases with isolated conotruncal defects 4 had microdeletion of chromosome 22q11.2 and concerning the first degree relatives in one case the father had the deletion without CHD.

Female↗

[Vertical transmission of the hepatitis C virus].

The incidence of hepatitis C in childhood is approximately 0.4%. The mode of transmission can be parenteral, sexual, occupational and also vertical. The latter has an incidence that varies widely and it increases in the case of human immuno-deficiency virus (HIV) coinfection and high titers of HCV in the mother. The vertical transmission is not influenced by breast feeding, however, data are discrepant with regard to child delivery (cesarean section vs vaginal delivery). Ninety-seven babies born from mothers with hepatitis C from 1996 to 1999, were evaluated prospectively in the Day Hospital of the Pediatric Department of Parma. The protocol of observation established a blood sampling for titers of antibodies anti-HCV and HCV-RNA at the 3rd trimester of pregnancy and subsequent clinical and biochemical controls at 3-6-9-12-15 and 18 months. Thirty (31.2%) out of the 96 mothers evaluated were positive for antibodies anti-HCV and 66 (68.8%) were positive for antibodies anti-HCV and HCV-RNA. Five (5.15%) out of the 97 babies evaluated were infected by HCV. Of these 4 were delivered vaginally and 1 by cesarean section. Of the 3 babies born to mothers with HIV coinfection, none was infected by HIV, but 1 was infected by HCV. Vertical transmission is increased by HCV viral load or HIV coinfection in the mother. The vaginal delivery and breastfeeding do not represent an additional risk factor.

Female↗

[Risk of materno-fetal transmission of the HIV infection with antiretroviral therapy and cesarean section: experience of the Parma group].

Vertical transmission of HIV is by far the most important way of infection in pediatric patients. Transmission rate of infection varies between 15-40% in the absence of antiretroviral prophylaxis. Only 2% of infected pregnant women who underwent caesarean section and zidovudine treatment transmitted the infection to their newborns. From January 1995 to September 2000 twenty seropositive pregnant women and their twenty newborns were followed at the Azienda Ospedaliera of Parma. Nine women (45%) were treated with only zidovudine according to the ACTG 076 protocol; eight women (40%) continued the treatment they were assuming before pregnancy with the eventual addition of zidovudine. 3 women (15%) were not treated because HIV infection was only detected after delivery. 15 women underwent caesarean section, in 13 cases in association to antiretroviral prophylaxis: in the remaining 2 cases no intrapartum treatment was started due to the urgency of delivery. The rate of vertical transmission among the 20 women was 5% (1/20), significantly less then that observed (20.5%) among 31 pregnant HIV women followed in Parma from January 1987 to December 1994 and not treated with antiretroviral prophylaxis and/or cesarean section (Magnani G. Personal data). The only infected baby was born by vaginal delivery. No transmission was observed in the group of pregnant women who underwent the combination of antiretroviral prophylaxis and cesarean section.

Anti-HIV Agents↗

[Early discharge and breast-feeding].

Early discharge is often correlated with negative events such as feeding problems leading to hypernatremic dehydration and malnutrition and non initiation or premature cessation of breastfeeding. In the reality of Parma we have valued the impact of early discharge on breastfeeding, analyzing a cohort of 267 dyads, 134 of which were in the "late discharge" group and 133 in the "early discharge" group. Our study showed, according to the most recent literature, that early postpartum discharge did not negatively affect the start and length of breastfeeding: early discharge indeed, if associated with suppression of "hospital routines" and with home-based postpartum follow-up visits, is a determining factor for the success of breastfeeding.

Breast Feeding↗

Identification of a 220-kDa membrane tumor-associated antigen by human anti-UK114 monoclonal antibodies selected from the immunoglobulin repertoire of a cancer patient.

Human monoclonal antibodies (HuMAb) specific for a 14-kDa perchloric acid-soluble protein (defined as UK114) were produced by somatic fusion of the human-mouse myeloma K6H6/B5 with Epstein-Barr virus-transformed peripheral B lymphocytes from a cancer patient previously treated with UK101 preparations, containing the UK114 protein. Three IgM-secreting clones were selected on the criteria of specificity for the purified UK114 protein immobilized onto plastic and adapted to grow in a serum-free medium. The reactivity of these antibodies showed a broad distribution pattern restricted to fresh tumor tissues and tumor cell lines, mainly of the adenocarcinoma type. None of the normal cells, nonmalignant cell lines, and normal tissues surrounding the neoplastic lesions were reactive. The immunochemical analysis of the target antigens showed that the HuMAb recognize a molecule of 220 kDa selectively expressed by the surface of tumor cells, as well as a cytoplasmic 14-kDa protein. The 220-kDa antigen was different from other tumor-associated antigens with similar molecular mass and, so far, unique. In the presence of human complement, two of three HuMAb are cytotoxic for tumor cells expressing the 220-kDa surface antigen. The tumor specificity and the lytic ability attributed to these HuMAb are promising features for the exploration of future clinical applications.

Animals↗

Consistency achieved by 23 European pathologists from 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas. European Commission Working Group on Breast Screening Pathology.

A detailed analysis of the consistency with which pathologists from 12 different European countries diagnose and classify breast disease was undertaken as part of the quality assurance programme of the European Breast Screening Pilot Network funded by the Europe against Cancer Programme. Altogether 107 cases were examined by 23 pathologists in 4 rounds. Kappa statistics for major diagnostic categories were: benign (not otherwise specified) 0.74, atypical ductal hyperplasia (ADH) 0.27, ductal carcinoma in situ (DCIS) 0.87 and invasive carcinoma 0.94. ADH was the majority diagnosis in only 2 cases but was diagnosed by at least 2 participants in another 14, in 9 of which the majority diagnosis was benign (explaining the relatively low kappa for this category). DCIS in 4 (all low nuclear grade) and invasive carcinoma (a solitary 1-mm focus) in 1. The histological features of these cases were extremely variable; although one feature that nearly all shared was the presence of cells with small, uniform, hyperchromatic nuclei and a high nucleo-cytoplasmic ratio. The majority diagnosis was DCIS in 33 cases; kappa for classifying by nuclear grade was 0.38 using three categories and 0.46 when only two (high and other) were used. When ADH was included with low nuclear grade DCIS there was only a slight improvement in kappa. Size measurement of DCIS was less consistent than that of invasive carcinoma. The majority diagnosis was invasive carcinoma in 57 cases, the size of the majority being 100% in 49. The remainder were either special subtypes (adenoid cystic, tubular, colloid, secretory, ductal/medullary) or possible microinvasive carcinomas. Subtyping was most consistent for mucinous (kappa, 0.92) and least consistent for medullary carcinomas (kappa, 0.56). Consistency of grading using the Nottingham method was moderate (kappa=0.53) and consistency of diagnosing vascular invasion, fair (kappa=0.38). There was no tendency for consistency to improve from one round to the next, suggesting that further improvements are unlikely without changes in guidelines or methodology.

Breast Diseases↗

Mixed medullary-follicular thyroid carcinoma. Molecular evidence for a dual origin of tumor components.

Mixed medullary-follicular carcinomas (MMFCs) are tumors of the thyroid that display morphological and immunohistochemical features of both medullary and follicular neoplasms. The histogenetic origin and possible molecular mechanisms leading to MMFCs are still unclear. To address these questions, we have isolated the two histological components of 12 MMFCs by (laser-based) microdissection, analyzed them for mutations in the RET proto-oncogene and allelic losses of nine loci on six chromosomes, and studied the clonal composition of MMFCs in female patients. Our results provide strong evidence that the follicular and medullary components in MMFCs are not derived from a single progenitor cell, because the seven tumors amenable for analysis consistently exhibited a different pattern of mutations, allelic losses, and clonal composition. We also demonstrate that follicular structures in MMFCs are often oligo/polyclonal and more frequently exhibit hyperplastic than neoplastic histological features, indicating that at least a subset of MMFCs are composed of a medullary thyroid carcinoma containing hyperplastic follicles.

Adult↗

Perchloric acid-soluble proteins from goat liver inhibit chemical carcinogenesis of Syrian hamster cheek-pouch carcinoma.

Chemically induced Syrian hamster cheek-pouch squamous cell carcinoma is very similar to the corresponding human tumour. This paper describes a blind study in which inhibition of dimethylbenzanthracene-induced cheek-pouch tumours by a goat liver extract denominated UK101 was investigated. Less than 40% of animals treated with UK101 developed tumours compared with 100% of the controls. Intermediate results (80%) were noted in a positive control group treated with Calmette-Guerin bacillus. Immunocytochemical testing of cheek-pouch mucosa by Mib5 showed significantly less proliferating cells in UK101 animals than in the controls. The effect of UK101 was completely reversed when dexamethasone was added in a third control group. A significant difference in complement-mediated cytotoxicity was noted in the sera of UK101-tested and control animals. These findings suggest that an immune mechanism is responsible for the inhibition of hamster cheek-pouch carcinoma by UK101.

9,10-Dimethyl-1,2-benzanthracene↗

Oncocytic and oncocytoid tumors of the exocrine pancreas, liver, and gastrointestinal tract.

Tumors having typical oncocytic features very rarely affect the gastrointestinal (GI) tract, liver, and pancreas, although several tumors with prominent "pink" (eosinophilic) cytoplasm are recognizable in the digestive tract. From a practical point of view, interest in the former lesions is limited to the differential diagnosis of a primary neoplasm versus metastatic deposits of malignant oncocytic tumors from other sites. This article briefly reviews the diagnostic features and clinical significance of the currently known tumors of the alimentary tract displaying a prominent oxyphilic character.

Adenoma, Oxyphilic↗