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Biomedical subjects

L Losi

Publications and source records attributed to L Losi.

At least 19 recordsLinked to original sources
PubMed1998

Molecular characterization of intraductal breast carcinomas.

In situ duct carcinoma (DCIS) is a heterogeneous group of lesions which has recently been subdivided into three types: well-differentiated (type I), intermediately differentiated (type II) and poorly differentiated (type III) DCIS. Fourteen cases of DCIS and 11 of DCIS with minimal invasion were analysed for mRNA levels of beta-actin, EGFR, c-cerbB2, MTS1, k-ras, RB, BRCA1, cyclin E, and c-myc genes. A microdissection technique was used on paraffin-embedded tissue. A statistically significantly higher expression of cyclin E oncogene and MTS1 tumor suppressor gene was seen in type III DCIS than in the other types, while no significant differences in the mRNA expression patterns of the other genes were observed. These data are consistent with the fact that poorly differentiated DCIS is a readily recognizable class of tumours that have a particularly aggressive behaviour and probably unique histogenesis.

Biomarkers, Tumor↗
PubMed1998

Identification of mitochondria in liver biopsies. A study by immunohistochemistry, immunogold and Western blot analysis.

Hepatocytes are rich in mitochondria, which play an important role in hepatic metabolism. In certain pathologic conditions (most often alcoholic liver disease) mitochondria became enlarged; nevertheless, even in these conditions they are hardly detectable on light microscopy. Recently an antimitochondrial antibody (mAM), which recognizes a 60-kDa protein, has been characterized. The purpose of the present study was to study immunoreactivity of this antibody in a series of liver biopsies. We studied 146 liver biopsies using an mAM. In 8 cases an ultrastructural study was also done, and in 2 cases Western blot analysis was performed. Cases were divided as follows: alcoholic liver disease (ALD, 31); steatosis (8); nonalcoholic steatohepatitis (NASH, 1); hepatitis C virus (HCV)-related hepatitis (83); hepatitis B virus (HBV)-related hepatitis (6); primary biliary cirrhosis (1); sclerosing cholangitis (1); haemosiderosis (1); sarcoidosis (1); alpha-1-antitrypsin deficiency (1); nonspecific findings (12). All the patients were investigated for alcohol or drug abuse, pharmacological treatment, hyperlipidaemia, hypercholesterolaemia and diabetes. Immunoreactivity was diffuse in cases of ALD, NASH and steatosis, and in patients with drug abuse. Electron microscopic immunogold and Western blot analysis confirmed that in the conditions examined the protein recognized by the mAM showed greater expression. Immunohistochemical staining was helpful in demonstrating a toxic or a metabolic insult even in cases in which the histological picture was blurred by viral infection.

Adult↗
PubMed1998

Intracranial germ cell tumour (embryonal carcinoma with teratoma) with complex karyotype including isochromosome 12p.

We report the chromosomal characteristics of a malignant teratoma with embryonal carcinoma component located in the pineal region of a 15-year-old boy. Chromosome analysis showed a near-triploid complex karyotype (62 chromosomes), including two copies of an isochromosome 12p, confirmed by fluorescence in situ hybridization analysis. The present findings indicate that isochromosome 12p formation is probably associated with the development of malignant germ cell tumours.

Adolescent↗
PubMed1998

Aberrant crypt foci in patients with colorectal cancer.

Aberrant crypt foci (ACF) are clusters of abnormally large colonic crypts identified on the mucosal surface of the human colon. They are thought to be preneoplastic lesions. The aim of the present study was to compare density (number of ACF per square cm of mucosal surface), crypt multiplicity (number of crypts per ACF) and histology of ACF in colonic resections of colorectal cancer patients resident in two Italian provinces with a twofold difference in colorectal cancer incidence rates. Thirty-two and 26 colonic resections were collected after operation in Ragusa (Southern Italy) and Modena (Northern Italy), respectively, and fixed in 10% formalin. Mucosal layers were observed under a light microscope at 25x after staining with methylene blue. Density of ACF was significantly higher in Modena (median 0.101 ACF cm(-2)) than in Ragusa (0.049, P = 0.001), whereas there was no difference in crypt multiplicity. ACF were classified into three groups according to histological features: ACF with mild alterations (hypertrophic ACF, 73%), ACF with hyperplasia (hyperplastic ACF, 17%) and ACF with dysplasia (microadenomas, 10%). The proportions of ACF in the three groups were similar in the two provinces. Density of ACF was higher and crypt multiplicity lower proceeding from proximal to distal large bowel. Microadenomas were observed only in the colon, whereas hyperplastic ACF were more frequent in the rectum. In conclusion, density of ACF correlates with colorectal cancer rates in two Italian provinces, and shows a positive gradient from proximal to distal large bowel. Histology of ACF suggests that they may be precursors of both hyperplastic and adenomatous polyps. These data provide further evidence of the role of ACF in human colorectal carcinogenesis.

Aged↗
PubMed1998

Oncocytic carcinoma (malignant oncocytoma) of the breast.

Three cases of oncocytic carcinoma of the breast observed in two women and one man are reported. One tumor was in situ and two were invasive. All three tumors were composed mostly of cells with "low-grade" nuclei and abundant granular eosinophilic cytoplasm. More than 70% of the neoplastic population in each case was immunoreactive with an antimitochondrion antibody. The presence of numerous mitochondria also was demonstrated at the ultrastructural level. Apocrine cells and oncocytes share similar morphologic features at the hematoxylin-eosin level; however, there are some differences that allow a confident distinction between these two cell types. Mitochondria in apocrine cells usually are in a perinuclear location and are not so numerous and diffusely dispersed as in oncocytes. In addition, apocrine cells display features of active secretory elements: prominent microvilli, well-developed Golgi complex, and electron dense secretory granules polarized toward the luminal pole; all these features were lacking in the three cases described. The cells constituting the present cases were not positive at the immunohistochemical and molecular levels for GCDFP-15/PIP mRNA, which are typical markers of apocrine differentiation. We suspect that mammary oncocytoma is a more common tumor than the meager number of reported cases suggests.

Adenoma, Oxyphilic↗
PubMed1998

[Intracranial location of a case of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) mimicking meningioma].

Sinus histiocytosis with massive lymphadenopathy was first described in 1969 in lymphnodes by Rosai and Dorfman ad subsequently in other organs including skin, bone ad soft tissue. Extranodal involvement has also been recognised, but central nervous system manifestations are extremely rare and clinical and radiological findings are suggestive of meningioma. We report a meningeal nodule in a young woman, clinically diagnosed as possible meningioma. A review of literature of previously reported intracranial lesions is presented.

Adult↗
PubMed1997

K-ras and p53 mutations in hereditary non-polyposis colorectal cancers.

Genetic instability related to defective DNA mismatch repair genes may be involved in the pathogenesis of carcinoma in Hereditary Non-Polyposis Colorectal Cancer (HNPCC). To test that the targets of genetic instability could include critical transforming genes involved in colon tumor progression, we examined 23 colorectal carcinomas in patients with HNPCC in order to detect somatic mutations in K-ras and p53 genes. Using single strand conformation polymorphism followed by direct DNA sequencing, we detected 4 mutations in K-ras gene (17%) and 3 in p53 gene (13%) which change the amino acid sequence of the protein p53. This is significantly lower than in sporadic cancer. Our data suggest that colon cancer in HNPCC might partly involve a distinct pathogenetic mechanism that involves other genes than those altered in sporadic tumors.

Adult↗
PubMed1997

Immunohistochemical localization of Bcl-2 and Bax proteins in in situ and invasive duct breast carcinomas.

Bcl-2 and Bax proteins are coded by a family of genes that take part in the manteinance of the balance between cell proliferation rate and programmed cell death in multicellular organisms. The Bax gene acts as promoter of cell death by opposing the death protector effect of the Bcl-2 gene. Expression of the Bcl-2 and Bax proteins has been investigated in 58 cases of duct carcinoma in situ (DCIS) and duct invasive and invasive lobular carcinomas (IC) of the breast. While both proteins were expressed at the same time in normal and benign epithelium, different staining patterns were observed according to the degree of differentiation of the neoplastic epithelium. In well-differentiated DCIS and grade I IC there was a predominance of Bcl-2 protein staining. Grade II lesions co-expressed both proteins. Poorly differentiated DCIS displayed a predominantly Bax protein staining pattern. Therefore, it appears that Bax protein expression, especially in DCIS, relates to more aggressive neoplasms while Bcl-2 protein expression is associated with less aggressive malignant lesions.

Breast Neoplasms↗
PubMed1997

Histology of aberrant crypt foci in the human colon.

Aberrant crypt foci (ACF) have been identified in the methylene-blue stained mucosa of the human colon. Some lines of evidence suggest that ACF may be precursors of colon cancer. The objective of the present study was to establish morphological criteria able to define and classify ACF in histological sections. Twenty-four colectomy specimens were collected after operation for colorectal cancer and fixed in 10% formalin. Strips of grossly normal mucosa were stained in a 0.2% solution of methylene blue in saline for 5-10 min. The strips were measured, put on a glass slide and observed under a light microscope at x25. One hundred and fourteen ACF identified by topology were sectioned parallel to the muscularis mucosae. Eighty-four ACF were evident at histological examination and could be classified into three main groups: group A (61 ACF, 72.6%) including foci whose epithelial cells had regular nuclei, with only mild or focal crowding but no stratification, no mucin depletion and no dysplasia; group B (16 ACF, 19.1%), in which features of hyperplasia were evident; and group C (seven ACF, 8.3%) including foci with enlarged, crowded and stratified nuclei, mucin depletion, frequent mitoses, and evident dysplasia, diffuse or focal (mild in five cases, moderate in two) representing microadenomas. Finally, hyperplastic foci were significantly larger than foci of group A and C. Group B ACF were also more frequent in the rectum than in the colon. In conclusion, selected histological features allow the definition of groups of ACF, which may represent sequential steps in the development of human colorectal tumours.

Aged↗
PubMed1997

Extraventricular neoplasms with neurocytoma features. A clinicopathological study of 11 cases.

The clinicopathological features of a series of neuronal and mixed neuronal and astrocytic neoplasms of the CNS are described. Patients were aged 5 to 63 years. Six cases were composed predominantly of small round cells with clear cytoplasm resembling central neurocytoma but lacked the characteristic intraventricular location of that tumor. The remaining five cases had similar neurocytomatous features associated with a benign astrocytic component. Ganglion cells and hyalinization vessels were observed in both groups. The growth fraction evaluated with monoclonal antibody Ki67Mib1 was low, ranging from 1 to 1.5%. Immunohistochemical detection of synaptophysin played a crucial role in identifying the neuronal nature of these neoplasms and was instrumental in distinguishing them from oligodendrogliomas, with which they are readily confused. The neuronal nature of the oligodendroglial-like cells was confirmed ultrastructurally in one case. The present cases, together with others reported previously, suggest that neoplasms of the CNS with "neurocytic" components are more frequent than generally assumed and expand the morphologic spectrum of neuronal and mixed neuronal-glial tumors. Except for one patient who died postoperatively, all patients were alive at follow-up ranging from 6 to 80 months.

Adolescent↗
PubMed1997

Colorectal carcinoma in different age groups: a population-based investigation.

Although colorectal cancer is a disease of the older population, these tumors are not infrequent before the age of 55. Through the data of a population-based registry, we proposed giving a description of the clinical features of three groups of patients in whom the disease occurred at a relatively early age of onset (group I: < 40 yr; group II: 41-50 yr; group III: 51-55 yr). There were only 14 patients under the age of 40 yr (1.1% of total registered patients, n = 1298 in the period 1984-1992). Group II and III represented 5.9% and 6.0%, respectively (n = 76 and 78), with minor fluctuations throughout the 9-yr period of registration. Inherited colorectal tumors [hereditary nonpolyposis colorectal cancer (HNPCC), adenomatosis coli, and suspected HNPCC] accounted for 38.4% of group I patients (5 of 14), 17.1% of group II, 10.2% of group III, and only 3.5% of individuals older than 55 (p, for trend, < 0.001). Thus, hereditary colorectal tumors were detected significantly more often in younger individuals. The majority of colorectal malignancies were localized in the left colon or rectum in all three groups, with a tendency (not significant) to a preferential localization in the right colon for tumors developed in group I (37% vs 18% and 14% in groups II and III, respectively). Pathological stage and main histological types did not differ among the three groups. Finally, life-table analysis did not show significant differences in 5-yr survival among the three groups; however, when considered together, early onset cases showed a more favorable prognosis than older individuals (log-rank 11.6; p < 0.001). In conclusion, colorectal cancer is diagnosed very rarely before the age of 40 yr, whereas about 12% of all cases belong to the age group 41 to 55 yr of age. Hereditary tumors were found more frequently in younger patients, with a well-defined inverse relationship between age of onset and frequency of genetically determined tumors. Finally, the clinical outcome was more favorable in the whole series of early onset cases than in older registered patients.

Adenocarcinoma↗
PubMed1997

[Evaluation of interlaboratory results of immunohistochemical techniques].

The aim of the present paper was that of evaluating stains obtained with immunohistochemical methods performed in different laboratories. Serial sections obtained from the same paraffin block were used. Each laboratory was asked to use their respective current methods. The antibodies requested to be used were anti-oestrogen and progesterone receptors ad Ki-67, irrespective of the source. A great range of different results was obtained, when the several stains were evaluated, including the haematoxylin-eosin stain. It is suggested that a better harmonization among different laboratories is necessary.

Antibodies, Monoclonal↗
PubMed1997

[Expression of estrogen receptors in breast cancer detected by various methods: lack of correlation].

Three methods are currently available for defining the estrogen receptor (ER) status in breast carcinomas. These include biochemical ligand binding assay (LBA), immunohistochemical (IC) and mRNA in situ hybridization (ISH) semiquantitative analysis. There is still a debate as to which method should be considered the "gold standard" to define ER status. To address this topic we evaluated the above three methods in a series of 43 breast neoplasms. The results of IC (on fixed sections with ER1D5 immunostaining) and LBA assay showed moderate correlation (p = 0.004), as there were 8 (18.6%) discrepant results. ISH was extremely sensitive, with 92% of positive results. ISH results did not correlate with either IC or LBA. In view of the relative lack of reciprocal correlation among the three methods, it is difficult to define which is the most accurate system to be used to localize ER in breast carcinomas. The easiest and least expensive method probably should be used. The immunohistochemical approach has the advantage of being easily applicable to routinely fixed material, to cytological specimen and is very useful in small lesions identified with mammography only.

Antibodies, Monoclonal↗
PubMed1996

Frequency and clinical features of multiple tumors of the large bowel in the general population and in patients with hereditary colorectal carcinoma.

BACKGROUND: Reports on the frequency of multiple carcinomas of the colon and rectum have varied from 3-4% to more than 10% of all tumors of the large bowel. METHODS: We reviewed the files of a specialized colorectal cancer registry with the following objectives: a) to determine the frequency of multiple tumors (synchronous or metachronous) in the general population; b) to compare these values with those observed in patients with hereditary nonpolyposis colorectal carcinoma (HNPCC); and c) to evaluate the clinical outcome of patients with multiple tumors and the role of other clinical parameters in the development of these neoplasms. RESULTS: From 1984 to 1992, 53 patients with multiple tumors (of 1298 registered patients, 4%) had large bowel carcinoma; 33 (2.5%) were synchronous and 20 (1.5%) metachronous. The total number of multiple colorectal carcinomas was 95, which was 7% of all registered colorectal carcinomas (1337 carcinomas in 1298 patients). Multiple tumors occurred significantly more often in patients with HNPCC than in those with sporadic carcinomas (P < 0.001); this increased prevalence was more marked for metachronous lesions, which occurred almost 4 times more often in patients with HNPCC (5.8% vs. 1.3%; P < 0.001). The average interval of time between the first and the second malignancy was 8.7 years; there was no significant difference between hereditary and sporadic tumors. Patients with synchronous tumors did not show appreciable differences in survival when compared with individuals who had single neoplasms. In contrast, a poor clinical outcome was observed in patients with metachronous tumors after the development of the second carcinoma. Finally, polypoid adenomas of the large bowel were found significantly more often in patients with multiple primary tumors than in those with a single tumor. CONCLUSIONS: These results emphasize the importance of preoperative pancolonoscopy for the identification of possible synchronous tumors (both benign and malignant) and long-lasting endoscopic follow-up for the detection of recurrent or metachronous lesions. The conclusions are even more pertinent for patients with HNPCC, whose risk of metachronous tumors is significantly higher than that of patients with sporadic carcinoma.

Aged↗
PubMed1996

K-ras and p53 mutations in human colorectal aberrant crypt foci.

Aberrant crypt foci (ACF) are putative precursor lesions of colon cancer, recently identified on the methylene blue-stained mucosal surface of human colon. No mutations in K-ras or p53 genes were found by non-radioactive single-strand conformation polymorphism analysis in 14 ACF collected from five patients. Using the more sensitive method of allele-specific polymerase chain reaction (PCR) for K-ras, 8 of 14 ACF were found to contain K-ras mutations, suggesting that mutated cells are present in minute clones in ACF. No dysplasia was observed in any of the ACF containing a mutated clone. The presence of K-ras mutations in ACF suggests that these lesions occur at a very early stage in human colorectal carcinogenesis.

Colon↗