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Biomedical subjects

G Mariuzzi

Publications and source records attributed to G Mariuzzi.

17 recordsLinked to original sources

Quantitative study of ductal breast cancer progression: nuclear signatures for evaluation of progression grade.

The evaluation of progressive morphological changes, with 93 morphometric parameters in tissue lesions representative of ductal breast cancer progression, has been performed in order to define in great detail the profile of chromatin texture (nuclear signature) changes. A gradual, distinctive increase in nuclear signature alterations from hyperplasia to infiltrating carcinoma has been found. The nuclear signatures' analysis of microinfiltrating foci in comedo DCIS showed sharp differences compared with those of comedo DCIS they derived from: these foci consist of cells with smaller and also more homogeneous nuclei. Opposite to the prominent heterogeneity of those of comedo DCIS: they appear to express a reduced clonality in the new, more progressed, cell population. Digital analysis of chromatin patterns seems to be useful, beyond mere extraction of individual features of value, in getting objective data for individual grading and prognosis of breast cancer.

Breast Neoplasms↗

Quantitative study of ductal breast cancer progression: signatures of nuclei in proliferating breast lesions and in situ cancer.

AIMS: The objective of this study is to derive highly specific nuclear signatures (NS's) for the characterization of nuclei of ductal breast epithelium in proliferative lesions and in situ cancers in order to evaluate if nuclear structural changes are able to describe the main events of ductal cancer progression and if the method can be used for objective grading. METHODS: A total of 82 different features descriptive of the nuclear chromatin patterns were computed in nuclei from normal glandular breast tissue, florid hyperplasia, and ductal carcinoma in situ (DCIS) and of DCIS with microinfiltration. The feature values were arranged to form a profile or signature. Measures of difference to a standard profile derived from normal glandular breast tissue were defined. One may then compute a standardized distance measure for a nucleus from "normal". Lesions can be characterized in the same manner, on the basis of the mean profile for all of their nuclei, and on the basis of the distribution of distances of their constituent nuclei from normal. RESULTS: The selected histopathologic patterns on which the diagnostic categories for DCIS are based were found to have corresponding distinctive patterns in the chromatin of the lesion's nuclei. A monotonic trend of ductal neoplastic progression was found. In addition, lesions histologically assessed as belonging to the same diagnostic category were found to offer substantially different distribution patterns. CONCLUSIONS: The full utilization of nuclear texture features allows the derivation of highly specific signatures for nuclei so that a reproducible grading can be performed for prognostic purposes.

Breast↗

Quantitative study of ductal breast cancer--patient targeted prognosis: an exploration of case base reasoning.

Current analytic methodologies allow the extraction, even from small tumor masses, of extensive information on the biologic characteristics of malignant lesions, such as tumor aggressivity, metastatic potential, drug resistance, and host interactions. Clinical practice now offers a wide range of therapeutic strategies. Information technological advances offer the opportunity to refer to very large data bases of patient anamnestic data, response to treatment and clinical outcome. There is a need to formulate therapy and prognosis for each individual case. Case based reasoning is a knowledge based methodology where the outcome for complex situations can be predicted by referring to a large data base of cases of known outcomes. The preliminary data obtained from this study suggest that case based reasoning may offer a promising approach to individual targeted prognosis.

Breast Neoplasms↗

Automated reasoning system in histopathologic diagnosis and prognosis of prostate cancer and its precursors.

OBJECTIVE: This article presents the rationale and options offered to diagnostic and prognostic decision support systems for prostate pathology by automated reasoning capabilities. METHODS: The symbolic information used in diagnostic decision-making is systematically ordered, compared, numerically assessed in its probability, and combined such that a conclusion can be drawn. The framework for the processing of such symbolic information may be an expert system, an inference network or a case-based reasoning system. Automated reasoning is implemented by the use of a rule base and information flow control modules. RESULTS: Automated reasoning allows decision support systems to follow highly adaptive decision sequences, capable of handling contradictory evidence, exceptions in diagnostic clue expression, and nonmonotonic decision-making. CONCLUSIONS: Automated reasoning capability in diagnostic and prognostic decision support systems allows highly flexible decision development, very close to human decision procedures.

Artificial Intelligence↗

Pancreatic cancer in Europe: Ki-ras gene mutation pattern shows geographical differences.

Seventy-seven pancreatic adenocarcinomas (60 Spanish and 17 Italian) were tested for Ki-ras gene mutations by analysis of polymerase chain reaction amplified sequences. Mutations involving codon 12 (GGT; gly) were detected in 16 Italian and 46 Spanish cases (80.5% in total). All Italian mutations involved the second base and were G to A transitions (GAT; asp) in 8 cases and G to T transversions (GTT; val) in the remaining 8. Forty-two Spanish mutations were characterized. Thirty-eight were at the second and 4 at the first base: asp in 24 cancers, val in 14, arg (CGT) in 2 and cys (TGT) in 2. Previous European studies and our present data show that 149 of the 186 pancreatic cancers harbored a codon 12 Ki-ras mutation (80%), the large majority affecting the second base (73%), with a transitions/transversions ratio of 1.3:1. However, the mutational pattern of cancers of the different European countries shows remarkable differences, both in the site of the mutation (first or second base) and in the ratio of transitions over transversions. Moreover, a significant subgroup of pancreatic carcinomas do not harbor Ki-ras mutations. The classification of pancreatic cancers, according to the presence or absence, and type of Ki-ras mutation, may be of importance in epidemiological studies. A critical reappraisal of existing epidemiological data, through a retrospective genotypic study using paraffin-embedded cancer samples, may reveal significant correlations with specific genotoxic agents.

Adenocarcinoma↗

Evolutionary somatic cell changes in cervical tumour progression quantitatively evaluated with morphological, histochemical and kinetic parameters.

The somatic cell changes which characterise malignancy evolution in human cervical preneoplastic and neoplastic lesions have been assessed on histological sections by means of a computerised image analyser. Many features have been simultaneously measured on each cell of the lesions studied, and the following results have been obtained: Some features, mainly kinetic, show continuously increasing values which express changes correlated to the increasing malignancy; other features, especially related to nuclear atypia, cellular heterogeneity and the degree of aneuploidy, have values dropping at the level of early stromal infiltration, which can be morphometrically characterised as composed of relatively homogeneous phenotypes; these features seem to express the degree of genetic instability and relate to the evolutionary somatic cell changes; tumour progression evolves through sequential discontinuous steps, each of them characterised by specific phenotypical features of the neoplastic cell population; the neoplastic cells in the foci of early stromal infiltration and vascular invasion, phenotypically more homogeneous than the parent cell populations of carcinoma in situ and infiltrating carcinoma, seem to possess a greater genetic stability.

Aneuploidy↗

Cytometric evidence that cervical intraepithelial neoplasia I and II are dysplasias rather than true neoplasias. An image analysis study of factors involved in the progression of cervical lesions.

Image analysis was performed on 40 Feulgen-stained histologic samples and 48 Feulgen-stained cytologic preparations representing normal squamous epithelium and all grades of cervical lesions (from mild dysplasia to invasive carcinoma) in order to characterize the evolutionary progressive changes in cervical epithelial proliferative disease toward malignancy. Quantitative studies included the analysis of proliferative features, differentiation features, nuclear morphology and DNA content. The data obtained on the histologic sections showed that the various features, to a different extent, detected a gradual increase in phenotypic cellular disarrangements related to the progression of the cervical lesions toward malignancy--that is, the modifications to nuclear area, perimeter, DNA content, percentage of nuclei with nucleoli, nuclear/cytoplasmic ratio and percentage of cells with no membrane positivity for soybean agglutinin lectin were progressively greater, moving from normal epithelium and mild dysplasia toward infiltrating carcinoma. In particular, all the morphologic and histochemical features appeared to parallel a diploid reduction and the appearance of aneuploidy. The simultaneous evaluation of proliferation- and differentiation-related features, together with those of nuclear DNA content, showed two main successive preneoplastic lesions: one characterized by an increase in cell turnover without alterations in its organization and another by a true neoplastic disorder. The data obtained on sequential cytologic examinations showed that individual cell changes are detectable and seem basically to be characterized by the appearance of clusters of cells with somatic characteristics not observed in previous cytologic checks. From the results of our study, the cervical intraepithelial neoplasia (CIN) concept appears to be inaccurate. In fact, only CIN III (severe dysplasia/carcinoma in situ) lesions have the morphologic and proliferative alterations of true neoplasia. In contrast, CIN I and some cases of CIN II lesions lack these characteristics and seem to be properly classified as dysplasia, thus avoiding the term neoplasia, implicit in CIN. Moreover, the multivariate study of data sets of features related to the progressive somatic changes, both in histologically and cytologically studied cases, allows us to detect the steps of progression; they are marked by the appearance of cell clusters with qualitatively different phenotypic characters when compared to the cell populations from which they presumably arise. These results seem to provide a further argument against the CIN theory, which stresses the concept that progression is related only to a gradual numerical increase in an initially established phenotype with the characteristics of malignancy.

Biopsy↗

[Biology and differentiation of lymphocytes in the classification of lymphomas].

The classifications of non-Hodgkin's lymphomas are briefly discussed and the processes of proliferation and differentiation of B and T lymphocytes are analyzed. The B and T lymphocytes engaged in the immune response arise from precursor cells through a two-cycle process of proliferation and differentiation: the first cycle produces cells with antigen receptors of varying specificity (resting circulating B and T lymphocytes); the second cycle produces B and T type effector cells and "memory" cells. Each phase of B and T differentiation can give rise to a type of lymphoma; in fact, malignant lymphomas can be divided into categories of precursor B and T cell lymphomas, resting B and T cell lymphomas and activated B and T cell lymphomas. Hodgkin's lymphoma could be considered a lymphoma arising from activated cells with atypical phenotype, i.e. Hodgkin and Reed-Sternberg cells. These cells secrete cytokines which recruit lymphocytes, histiocytes, eosinophils and plasma cells which form the cellular background typical of this tumor.

B-Lymphocytes↗

Comparison of computerized analysis of nuclear DNA changes in uterine cervix dysplasia and in urothelial non-invasive papillary carcinoma.

The nuclear DNA content was measured in preneoplastic lesions of the uterine cervix and in papillary carcinomas of the bladder. Three groups of features were calculated from the raw data: basic DNA, DNA deviation and DNA distribution. The basic DNA features, concerning both the cervix and the bladder, showed a progressive increase in the mean DNA content, a decrease in the percentage of diploid nuclei and steadily increasing values of polyploid and aneuploid nuclei. Among the DNA deviation features, the malignancy grade value was zero in the normal cervical epithelium and in the normal urothelium. An increase in this value was evident in moderate dysplasia and in urothelial papillary carcinoma of grade 2, the highest value being in CIS and in grade 3. Concerning the DNA distribution features, the values of the 15th and 95th percentiles and their difference were progressively higher both in the cervix and in the bladder, expressing a continuous shift and spread of the DNA content measurements in the different diagnostic categories, with respect to normal epithelium and urothelium. The statistical analysis showed that the strongest correlation is between 2c D.I. and % of polyploid nuclei in the cervix and between M.I. and % of aneuploid nuclei greater than 4c in the bladder. In the cervix the most discriminating feature is the Malignancy Grade, whereas in the bladder it is the percentage of diploid nuclei. The comparison between the results of the three groups of features showed that: 1) Mild dysplasia of the cervix and urothelial papillary carcinoma of grade 1 showed similar changes in DNA features. Both were basically characterized by increased proliferative activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Papillary↗

Prognostic value of computerized DNA analysis in noninvasive papillary carcinomas of the urinary bladder.

DNA parameters and a DNA status index were calculated in cases of noninvasive urothelial papillary carcinomas and apparently normal urothelium. DNA feature analysis included the measurement of basic parameters as well as those related to DNA deviation. Normal urothelium had a diploid content with a few values between 2c and 4c. The papillary lesions in the three grades showed a progressive decrease in diploid nuclei and steadily increasing percentages of tetraploid ones. One case of grade 1 papillary carcinoma and some of grade 2 showed a small proportion of aneuploid cells; the proportion quintupled in grade 3. The values of parameters related to DNA deviation increased progressively in the three grades, numerically expressing the shift from diploidy. The DNA status index is a multiparameter classification in which a single number, ranging from 0.5 to 3.7, expresses the degree of DNA deviation from a non-proliferating diploid population. The cases of normal urothelium and of grade 1 had the lowest values, from 0.5 to 1.9, whereas grade 3 cases had the highest, from 2.2 to 3.7. The index values of grade 2 cases were partly intermediate and partly in the range of the neighboring grades. The DNA status index has a prognostic significance. In fact, associated lesions and recurrences were only observed in cases with index values over 2.0.

Carcinoma, Papillary↗

Benign and malignant mesothelial lesions of the pleura: quantitative study.

Benign and malignant mesothelial lesions of the pleura are quantitatively studied using a Leitz TAS image analyzing system. The Feulgen fast green staining method allows performing on the same cell measurements of the shape and size of the nucleus, the size of the nucleolus and the content of DNA. Numerical data are studied in a multivariate statistical analysis in order to obtain the probability of the morphometric diagnosis in each case. Results demonstrate that the most important measurements are the percentage of cells with evident nucleolus, the nuclear perimeter and the standard deviation of the DNA content, and that these measurements give a correct diagnosis in all cases.

Analysis of Variance↗

Noninvasive papillary transitional-cell tumors. Karyometric and DNA-content analysis.

An investigation was undertaken to quantify and correlate the nuclear and DNA-content modifications in the different grades of noninvasive urothelial papillary carcinoma. Nuclear area and a roundness factor were studied by histomorphometry in 35 cases, and the DNA content was analyzed in 27 cases. The values of the nuclear area and the roundness factor increased from normal-looking urothelium to grade 3 tumors. The DNA-content analysis indicated a progressive change of ploidy and the presence of an aneuploid (greater than 4c) population in some of the grade 2 and grade 3 lesions. A high coefficient of correlation between the nuclear abnormalities and the DNA content was found.

Aneuploidy↗

Multivariate quantitative histopathological assessment of prognostic factors in ductal infiltrating breast carcinoma.

The aim of this study was to evaluate the power of quantitative pathology in improving the accuracy of prognosis in ductal infiltrating breast carcinoma. Ninety tumours were studied, with a diameter < or = 2.5 cm; positive (metastatic) axillary lymph nodes were found in 48 of the 90 cases; no patient had systemic metastases. Surviving patients had a mean follow-up of 106 months (minimum 69 months). At the end of the study, 45 patients were alive, 45 deceased. The histopathologic study of tumour nuclei and nucleoli included: a) geometric features, i.e., the mean and standard deviation of nuclear area, perimeter, diameter and form factor, nucleolar area and nucleolar/nuclear ratio, measured with a Kontron-IBAS automatic image analyser; b) immunohistochemical features, i.e., the percentage of PCNA (Proliferating Cell Nuclear Antigen)-positive nuclei, the expression (positive or negative) of vimentin (as a marker of tumour dedifferentiation), and the nuclear protein p53. Statistically significant differences were found between surviving and decreased patients for most features; multivariate analysis gave 92.2% accuracy in predicting outcome. Among the classes defined with multivariate analysis, it was possible to distinguish subsets of patients with bad prognosis by studying the expression of vimentin and p53, although these markers were positive in a small number of cases: 5 out of 6 patients with vimentin positivity and 4 out of 8 with p53 positivity died within 24 months of the diagnosis.

Antigens, Neoplasm↗