Technology of building an expert system based on a set of quantitative features of tumor cell nuclei for diagnosing breast cancer.

The technology of building an expert system for diagnosing malignant nature of invasive tumors of the mammary gland based on a set of quantitative features of the cell nuclei has been developed. Its peculiarity was the presence of weighting coefficients in all the features. Quantitative features were obtained by transforming the initial morphometric data with the help of simple (evaluation of mean values and building of histograms) and complex (regression analysis) mathematical operations. The expert system consisted of one-dimensional X-matrix used for investigations and two-dimensional standard S-matrix. The X-matrix elements were assigned for filling with the quantitative features of the studied sample with a nonestablished diagnosis. The S-matrix elements contained threshold values of quantitative features from the system of diagnostic decision criteria for malignant forms of diseases and their weighting coefficients. Threshold values of nuclear features (larger or smaller) were determined taking into account the range of their values in the groups of malignant and benign pathology. Significance of quantitative features in diagnosing diseases has been assessed. The presence of weighting coefficients allowed diagnosing malignant and benign pathology in a quantitative form by the diagnostic index value. Diagnostic index was calculated by the sum of weighting coefficients of features of the studied sample, which fell within the range of system of the S-matrix diagnostic decision criteria. Clinical trials revealed high efficiency of the developed approach while diagnosis of breast cancer invasive forms at a preoperative stage.

[Study of nucleolar organizer regions in prostate cancer]. / Studiul regiunilor organizatoare nucleolare în tumorile prostatice.

AIM: To compare the qualitative and quantitative AgNOR scores per nucleus of histological grades. MATERIAL AND METHODS: Thirty-five needle biopsies from patients with prostate cancer (PC) aged 60 to 75 years were investigated. The morphologic parameters examined on histological specimens were: microscopic patterns, Gleason's histological grades (GLG), and AgNOR scores by automated image analyzer and quantitative AgNOR counts according to the classification, fine granules, large granules, and total granule counts. RESULTS: Our data suggest a significant correlation between GLG, AgNOR scores, and the percentage of both AgNOR fine and large granules. In HPIN, AgNOR count was evidently higher (5.56) as compared to normal acinar epithelium, slightly exceeding the level found in well-differentiated carcinoma (5.3). In our cases, the highest AgNOR counts were found in poorly differentiated carcinomas (9.81). AgNOR density in ductal carcinomas (7.61) was close to that in moderately differentiated carcinomas (7.35). CONCLUSION: This simple method may aid diagnostic judgement when interpreting needle biopsies of malignancy and act as a prognostic marker useful for identifying PC of low and high malignancy.

Surface topography and ultrastructural changes of mucinous carcinoma breast cells.

Mucinous carcinoma of the breast (MCB) is histologically classified into 2 groups: (1) pure MCB and (2) mixed MCB. Pure MCB carries a better diagnosis than mixed MCB. This research relates to the cell surface topography and ultrastructure of the cells in the above cases and aims to find the differences between them, by means of two methods: scanning electron microscopy (SEM) and transmission electron microscopy (TEM). For the SEM examination, it was necessary to initially culture the MCB tissues and then proceed with the usual SEM method. In contrast, for the TEM technique, MCB tissues were initially fixed followed by the classic TEM method. The authors found the topography of pure MCB cases to be without nodes. The cell membrane was smooth, with numerous pores and small ruffles that covered the entire cell. The ultrastructural appearance of the same cases was with a normal cell membrane containing abundant collagen fibers. They also had many small vesicles containing mucin as well as secretory droplets. In contrast the mixed MCB had a number of lymph nodes and their cell surface topography showed stronger changes such as microvilli, numerous blebs, ruffles and many long projections. Their ultrastructure showed very long microvilli with large cytoplasmic inclusions and extracellular mucin collections, electron-dense material vacuoles, and many important cytoplasmic organelles. An important fact is that mixed MCB also contains areas of infiltrating ductal carcinoma. These cells of the cytoplasmic organelles are clearly responsible for the synthesis, storage, and secretion of the characteristic mucin of this tumor type. Evidently, this abnormal mucin production and the abundance of secretory granules along with the long projections observed in the topographical structure might be responsible for transferring tumor cells to neighboring organs, thus being responsible for metastatic disease.

Studies on argyrophilic nucleolar organizer regions (AgNORs) in a spontaneous mammary gland ductal carcinoma of a captive rhesus monkey.

A spontaneous mammary gland ductal carcinoma was diagnosed in a 13-year-old female captive rhesus monkey (Macaca mulatta). The expression of argyrophilic nucleolar organizer regions (AgNORs) was studied to investigate the correlation between the histologic invasiveness and cell proliferation activity assay for predicting the biologic behavior of this tumor type. The results of this study show that the AgNOR size in tumor cells reflect the degree of malignancy when compared with the pattern of peripheral blood lymphocytes of the same individual. This is the first study showing a significant AgNOR feature of a malignant breast tumor in a rhesus monkey and it longs to provide additional diagnostic tool in tumor pathology.

Intestinal type adenocarcinoma: a previously unrecognized histologic variant of ductal carcinoma of the pancreas.

Adenocarcinomas with intestinal differentiation have been described in a wide variety of anatomical sites. To our knowledge, however, ductal adenocarcinomas with intestinal phenotype have not been described in the pancreas. We report here 11 ductal carcinomas of the pancreas that were morphologically similar to colonic adenocarcinomas. These pancreatic carcinomas of intestinal type represented 10% of 110 consecutively removed ductal carcinomas of the pancreas. All intestinal type carcinomas expressed cytokeratin 7, carcinoembryonic antigen, CDX2, and MUC2. The pattern of reactivity of cytokeratin 7 and carcinoembryonic antigen was diffuse, whereas that of mucin 2 staining and CDX2 nuclear labeling was focal and confined predominantly to goblet cells and less frequently to columnar cells. Six carcinomas contained collections of endocrine cells admixed with the columnar and goblet cells. Five carcinomas were associated with high-grade pancreatic intraepithelial neoplasia of intestinal type. Six patients were female and 5 were male. Their ages ranged from 52 to 76 years (mean age, 61 years). The clinical presentation did not differ from that of the conventional ductal carcinomas. All carcinomas originated in the head of the pancreas, and 5 had metastasized to the regional lymph nodes at the time of surgical resection. Only 1 patient survived 5 years. Three patients are disease free from 2.8 to 8.9 months after surgery. Six patients died as a direct result of the carcinomas, and 1 was lost to follow-up. More studies are needed to determine the biologic behavior of this distinctive histologic variant of ductal adenocarcinoma of the pancreas.

Ultrastructural immunostaining of infiltrating ductal breast carcinomas with the monoclonal antibody H: a comparative study with cytokeratin 8.

The monoclonal antibody H (mAbH) detects an epitope consisting of an O-linked N-acetyl glucosamine (O-GlcNAc) and neighboring amino acids. This epitope has been found by using extracts from the MCF-7 human breast carcinoma cell line in immunoblotting experiments, on cytokeratin 8 (CK8) and 5 other polypeptides. In the present study, a double immunogold method was applied for the colocalization of CK8 and mAbH epitope on epoxy thin sections in 18 cases of infiltrating ductal breast carcinomas (IDBC) and in 6 cases of fibroadenomas, to study the accurate subcellular distribution of CK8 in breast cancer cells, as compared to the 5 polypeptides, recognized by mAbH. Furthermore, a detailed quantitative evaluation of the double immunolocalization over the cellular compartments of cancer cells was undertaken with the aid of a computerized image analysis system and the results were assessed statistically. The distribution pattern of CK8 and the mAbH epitope in the neoplastic mammary epithelial cells was similar in IDBC as compared to fibroadenomas, while the gold labeling intensity of these epitopes differed over the cellular compartments between malignant and benign biopsies. The results reveal the significance of the role of CK8 and O-GlcNAc glycosylation in the biology of the neoplastic mammary cells in vivo, determining their malignant potential.

Salivary duct carcinoma: ultrastructural and histogenetic considerations / Carcinoma ductal de glândula salivar: considerações ultraestruturais e histogenéticas

Two cases of salivary duct carcinoma were examined by light and electron microscopy. Histologically, the tumor presented cribriform and papillary patterns together with comedonecrosis. Electron microscopy revealed duct cells with microvilli, interdigitations, and apical vesicles. No myoepithelial cells were observed. These findings suggest a ductal origin other than from the intercalated duct or its precursor element. The importance of separating the salivary gland adenocarcinomas is discussed