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PubMedDate not supplied

Relevance of ploidy related parameters for prognosis in malignant fibrous histiocytomas.

Ploidy associated parameters were determined in 161 malignant fibrous histiocytomas (MFH) by DNA image cytometry. The rate of euploid cases in MFH with histopathological grade I was 42%, grade II 16% and grade III 6%. Univariate analyses showed that cases with a low percentage of diploid cells (< 40%) and cases with high rates of aneuploid cells between 4c and 8c (> 9%), octaploid cells (> 0%) and 16-ploid cells (> 0%), high 2.5c (> 60%) and 5c (> 16%) exceeding rates and cases with high DNA indices of the first (> 1.08) and the second (> 3.78) peak had significantly reduced survival rates. Multivariate analyses with Cox regression demonstrated that in addition to grade, only the percentage of aneuploid cells between 4c and 8c, the 5c exceeding rate and the DNA index of the first peak had independent prognostic impact. It was concluded that besides ploidy status and grading, ploidy associated parameters are suited for prediction of survival in MFH.

Adolescent↗
PubMed1999

Prostate cancer induction in autoimmune rats and modulation of T cell apoptosis.

In this study we present an experimental model of prostate gland cancer induced by long term hormonal treatment with testosterone in combination with a chemical carcinogenic agent in male Wistar rats with autoimmune prostatitis (AIP). This system is particularly attractive in order to study the factors involved in the transition from a non-invasive to an invasive carcinoma, decisive in the risk of human cancer. At first, autoimmune prostatitis was induced by immunization in 3 months-old male Wistar rats with autologous accessory glands. Then, rats were treated with continuous intradermal implants of testosterone propionate (TP) and with single doses of the chemical carcinogen 7, 12 dimethylbenz (alpha) anthracene (DMBA) by intraperitoneal injection. Histopathological studies of the prostate gland revealed the presence of pre-malignant lesions, particularly the so-called prostatic intraepithelial neoplasm (PIN) in 50% of animals. Moreover, we observed the development of carcinomas in 50% of treated-animals, which could be histologically discriminated in adenocarcinomas, carcinoma of epidermal origin and undifferentiated carcinoma. In autoimmune rats which did not receive any other treatment, exposure to autoantigens gave rise to an atypical hyperplasia of the prostatic gland which could be attributed to the hyperactive state of the gland. Control groups constituted by autoimmune rats treated with TP or DMBA, and normal rats which were exposed to TP and/or DMBA evidenced the presence of PINs at different degrees, but did not develop carcinomas. Moreover, serum acid phosphatase significantly increased as treatment was accomplished, reaching its maximum levels in animals with carcinoma, in which DNA content, determined by image cytometry, showed to be aneuploid. Finally, we provided biochemical and cytofluorometrical evidence of the induction of apoptosis of spleen T cells in carcinoma-bearing hosts, and to a lesser extent in animals with PIN, but not in autoimmune or normal controls, which could represent an alternative molecular mechanism for explaining host immunosuppression triggered by tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Honest assessments of automatic learning algorithm performance.

OBJECTIVE: To compare methods of evaluating probabilistic predictors in systems that learn from examples. STUDY DESIGN: The performance of four automatic learning algorithms, representing current machine learning technology, were assessed using four methodologies in the task of separating normal squamous intermediate cervical cells from all other segmented objects in digital images. Two of the methodologies were carefully constructed to model sources of variation associated with the choice of training and test sets. These assessments were statistically compared with assessments using both standard and a modified version of cross-validation. RESULTS: The investigation illustrates the tradeoffs involved in obtaining statistical rigor as compared with the cost of collecting data. While cross-validation makes frugal use of data, it can produce misleading assessments of algorithm performance in terms of both bias and variance. The modified version produces more reliable assessments but in some cases may also be misleading. CONCLUSION: We suggest that users of learning algorithms should exercise judicious care in evaluating learning algorithm performance in order to avoid unnecessary bias and large variance in their assessments.

Algorithms↗
PubMed2000

Topologic distribution of different types of neurons in the human putamen.

OBJECTIVE: To test the assumption that the various types of neuron in the human putamen appear to be randomly distributed and to quantify the way in which they are arranged, stochastic geometry, multivariate analysis and the interactive evaluation technique were employed. STUDY DESIGN: Twenty-seven human putamina without demonstrable signs of neurologic change were dissected out, fixed in 4% formalin and embedded in paraffin. The 20-micron paraffin sections were stained in an aldehyde-fuchsin and cresyl-violet solution, which makes it possible to distinguish between seven different neuron populations in the putamen. The gravity centers, size and form factors of these neurons were determined morphometrically under a light microscope. The data obtained were used to calculate the spatial distribution of the neurons by interactive and structure analytical methods. RESULTS: Visual point field analysis revealed an irregular arrangement of the different types of neurons. Point process analysis detected a significant hard core process of type 1 and a cluster process of type 6 neurons. With nearest neighborhood analysis, significant differences were found between certain populations of neurons and Poisson processes. Comparison of the results of multivariate cluster analysis with the investigator-dependent results of visual point field analysis showed clear differences. CONCLUSION: By means of structure analytical methods, the arrangement of different populations of neurons can be demonstrated. Some neuronal distributions are detectable only by using one of these techniques. The question of random or nonrandom distribution of the neurons in the human putamen can now be answered definitively: arrangement of the different populations of neurons is structured.

Adult↗
PubMed2000

[Early stage ovarian carcinoma--diagnosis and treatment].

The prognosis of patients with early stage ovarian borderline tumour and carcinoma is good. In spite of this most patient management has been unnecessarily heavy. DNA ploidy is an independent and the strongest prognostic predictor of survival with an excellent prognosis in patients with diploid tumours, it should be included in the routine evaluation of patients in order to achieve optimal and individual management. Image cytometry is superior to flow cytometry in predicting prognosis.

Adult↗
PubMedDate not supplied

Comparison of the DNA content in liver cell adenoma, hepatocellular carcinoma and regenerative nodules.

With regard to neoplasms of hepatocytes, diagnostic pitfalls have been reported for differentiation of liver cell adenoma (LCA) from well differentiated hepatocellular carcinoma (HCC). Since cytophotometric analysis of the DNA content with the help of image analysis has proven to be of diagnostic value in various neoplasms, we examined its ability to discriminate between LCA and HCC as well as regenerative liver nodules. The material investigated consisted of 54 cases of HCC, 10 benign liver tumours and 10 cases suspicious for HCC. All the benign liver tumours demonstrated an euploid histogram. 9 out of 10 borderline tumours were euploid while 1 out of 10 was suspiciously aneuploid. Among HCC, 21 out of 54 were euploid, 18 out of 54 suspiciously and 15 out of 54 clearly aneuploid. 5c exceeding rate differed significantly between benign liver changes and borderline lesions (p = 0.0474) as well as between borderline lesions and malignant tumours (p = 0.0108). We conclude that the use of image cytometry is helpful as an additional criterion for more diagnostic accuracy in morphologically difficult cases.

Adenoma, Liver Cell↗
PubMed2000

Data representation and reduction for chromatin texture in nuclei from premalignant prostatic, esophageal, and colonic lesions.

BACKGROUND: To identify nuclei and lesions with great specificity, a large set of karyometric features is arranged in the form of a linear profile, called a nuclear signature. The karyometric feature values are normalized as z-values. Their ordering along the profile axis is arbitrary but consistent. The profile of the nuclear signature is distinctive; it can be characterized by a new set of variables called contour features. A number of data reduction methods are introduced and their performance is compared with that of the karyometric features in the classification of prostatic, colonic, and esophageal lesions. METHODS: Contour characteristics were reduced to descriptive statistics of the set of z-values in the nuclear signature and to sequence information. The contour features derived were (1) relative frequencies of occurrence of z-values and of their differences and (2) co-occurrence statistics, run lengths of z-values, and statistics of higher-order dependencies. Performance was evaluated by comparing classification scores of diagnostic groups. RESULTS: Rates for correct classification by karyometric features alone and contour features alone indicate equivalent performance. Classification by a combined set of features led to an increase in correct classification. CONCLUSIONS: Image analysis and subsequent data reduction of nuclear signatures of contour features is a novel method, providing quantitative information that may lead to an effective identification of nuclei and lesions.

Cell Nucleus↗
PubMed2000

[Effect of prenatal emotional-pain stress on the status of interphase chromatin in neurons of the rat developing brain with various excitation of the nervous system].

A short-term emotional-painful stress, experienced by pregnant rat females differing in threshold of excitability of their nervous system, was used to assess the state of interphase condensed chromatin and C-heterochromatin of neuron nuclei in developing brains of 16-17 day old embryos. To reveal relationships between the genetically determined excitability of rats and the state of interphase chromatin in their neuron nuclei a computer information system has been used that enabled us to classify the neuronal nuclei according to their specific DNA image cytometry features. The results indicate an obvious relationship between excitability of the nervous system and structural-functional state of the neuronal interphase chromatin.

Animals↗
PubMed2000

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↗
PubMed2000

Regular form factor. A new concept and calculating method for quantitative form description.

OBJECTIVE: To quantitatively describe the shape of two-dimensional particles based on combined consideration of area (A), circumference (C), and major and minor diameter (d1 and d2, respectively). STUDY DESIGN: A regular form factor (RFF), a new concept and calculating method for form description, was defined as the extent to which a structure differs from an ellipse or circle of which the major and minor diameters, respectively, are equal to the described structure. Based on the definition of RFF, formulae were deduced in accordance with mathematical principles. RESULTS: The deduced formulae were as follows: RFF = A [1.5(a + b) - square root of (a b)]/(a b C) and RFF = A [3 (d1 + d2) - 2 square root of (d1 d2)]/(d1 d2 C). In the formulae, a = d1/2, and b = d2/2. RFF = 1 for ellipses and circles, and < 1 for irregular particles. The more similar to an ellipse or circle, the closer to 1 is RFF. The more irregular the structures are, the smaller the values of RFF. An error analysis was also made, and a rectified formula for RFF was deduced. An example is given to show how to calculate RFF. A practical test of RFF was made in colorectal adenoma and adenocarcinoma in human material, and the results show that RFF of glands of colorectal adenoma and adenocarcinoma have significant differences between normal, adenoma and adenocarcinoma. CONCLUSION: RFF was compared with the parameter Form AR, and the results showed that RFF is more sensitive in describing the irregularity of a structure than Form AR. RFF is of practical significance for describing structures in human material.

Adenocarcinoma↗
PubMed2001

Chromosomal rearrangements and oncogene amplification precede aneuploidization in the genetic evolution of breast cancer.

Breast carcinoma is thought to arise because of multiple successive changes in the genome of the normal epithelial cells. However, little is known of the order of appearance of different types of genetic aberrations We studied the ERBB2 (Her-2/neu) and CCND1 (cyclin D1) oncogene amplification in flow cytometrically sorted diploid and nondiploid tumor cell populations by fluorescence in situ hybridization (FISH). The purity of the cell sorting was confirmed by static DNA image cytometry. Spectral karyotyping was used to define differences in a genome-wide manner between two distinctly different aneuploid cell clones found in each of two breast cancer cell lines. FISH indicated the presence of gene amplification both in diploid and nondiploid cell clones in 17 of the 21 amplification-containing tumors analyzed. The oncogene copy numbers remained unchanged throughout aneuploidization in 11 of 17 tumors. The remaining six tumors showed an increase in oncogene copy number as well as the number of chromosome 11 or 17 centromeres (the original location of CCNDI and ERBB2, respectively). Breast carcinoma cell lines MDA-157 and MDA-436 showed a significant number of chromosomal rearrangements in the near-diploid clones, which were present in duplicate in the corresponding aneuploid (polyploid) clones. These results indicate that ploidy shift, ie., aneuploidization, in breast cancer is a late genetic event which is preceded by both oncogene amplifications as well as many chromosomal rearrangements.

Aneuploidy↗
PubMedDate not supplied

Molecular genetic methods in the diagnosis of invasive bladder cancer.

Development and progression of tumours is generally driven by an accumulation of genetic alterations. In this study we correlated chromosome 17 aneuploidy to invasiveness of bladder cancer by the method of fluorescence in situ hybridisation (FISH) in urinary cytospins. We investigated the value of FISH compared to DNA cytophotometry in the diagnosis of bladder cancer. 39 patients with or suspicious for bladder tumour were analyzed. 19 patients had a bladder tumor at the time of diagnosis, 14 superficial (Ta-T1) and 5 invasive (T2-3). The remaining 20 patients had no tumour at the time of diagnosis, however 9 of them had one in prehistory (Ta-T2). For FISH we used the DNA probe of HER-2/neu located on chromosome 17. DNA image cytometry was performed according to single cell interpretation of Böcking. Our results showed a correlation between HER-2/neu CEP 17 alterations and invasive bladder cancer to the extent of 10-70% aberrant cells for patients with current invasive bladder tumour as well as for patients who had been cured but with as invasive bladder cancer in prehistory. On the other hand, the percentage of aneuploid cells for negative biopsy and superficial tumour was 0-2%. The DNA cytophotometry brought an uniform aneuploidy only for present invasive tumours: negative biopsies, superficial cancer and invasive tumour just in prehistory, showed mixed diploid-aneuploid DNA patterns. Our results showed that for the detection of aberrant tumour cells the method of FISH is more sensitive than DNA cytometry. FISH could provide important information in the prognosis of bladder cancer.

Adult↗
PubMed2001

Expression of enzymes and oncogene induced after radiotherapy and/or chemotherapy in patients with brain tumors.

The relationship between the degree of the expression of Cu/Zn SOD, GST-pi and bcl-2 in the initial and recurrent tumor tissue after radiotherapy and/or chemotherapy and the cellular heterogeneity obtained from DNA content by image cytometry was investigated. Subjects were 7 patients who had glial tumors which were surgically removed at onset and removed a second time at recurrence. Radiotherapy and chemotherapy were also administered after initial resection. Immunoreactivity for copper/zinc super oxide dismutase (Cu/Zn SOD), GST (glutathione-S-transferase)-pi, and bcl-2 were evaluated from routinely prepared tissue blocks. Tumors were classified into two groups by cytometric analysis of DNA ploidy in the G2M cell cycle phase. One tumor group consisted of single clonal cells in both the initial and recurrent tumors and the other group consisted of tumors with polyclonal cells in the initial and recurrent tumor. In this study, one patient (case 3) with single clonal cell glioblastoma at recurrence did not show high Cu/Zn SOD activity after radiotherapy and chemotherapy but showed a short survival time after recurrence. In three patients (cases 1, 2, 3) with single clonal-cell glioblastoma, the recurrent tumor cells showed high GST-pi immunoreactivity and survival time was short after recurrence. Tumor cells in two patients (cases 5, 7) with single clonal cell anaplastic glioma at recurrence, showed high GST-pi immunoreactivity and had a short survival time after recurrence. In three single clonal glioblastomas (cases 1, 2, 3), the recurrent tumor showed the increased bcl-2 immunoreactivity and showed a short survival time after recurrence. In two patients (case 5, 7) with single clonal cell anaplastic glioma at recurrence, tumor cells showed a high bcl-2 immunoreactivity and these patients showed a short survival time after recurrence. Although the number of subjects is very small, our study shows that the immunoreactivity of bcl-2 and GST-pi in malignant gliomas may be very important factors in radio- and chemosensitivity, and shows that GST-pi is induced by radiation and anti-cancer drugs.

Adult↗
PubMed1998

[Change of cell proliferation after the denervation laryngeal adducent muscles in dogs].

OBJECTIVE: To investigate the changes of cell proliferation state after denervation of laryngeal adducent muscles in dog. METHODS: The muscles were obtained from 8 dogs with recurrent lanyrgeal nerves injured. The cross sectional areas of muscle cells were measured by VIDS Image Analysis System in HE stained sections. A quantitative collagen/muscle ratio was measured by TJTY-300 image analysis system in Van Gieson stained sections. The percentages of S phase cell nucleus were calculated by image cytometry/DNA quantitative analysis with CAS 200 System. RESULTS: It showed that the cross sectional area of muscle cells decreased gradually after denervation (out-standing in 6 months after denervation) and collagen/muscle ratio increased significantly with time. The percentage of S phase nucleus was high at 5 months and then decreased. CONCLUSION: The proliferation of thyroarytenoid muscle and lateral cricoarytenoid muscle cell of dog remained at high level in 5 months after denervation and then slowed down and atrophy of muscles occurred 6 months after denervation. This suggests that nerve repair should be performed early. Examination of cell proliferation might indicate if the denervation of cells irreversible. It is helpful in choosing proper surgery and estimating the effect of nerve repair.

Animals↗
PubMed2001

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↗
PubMed2001

Corneal abnormalities in diabetes.

OBJECTIVE: To compare corneal thickness and endothelial morphology in patients with diabetes mellitus and age-matched normal subjects, and to determine whether the duration of diabetes mellitus, severity of diabetic retinopathy, and glycemic control are correlated with these measurements. DESIGN: Single center, case-control study. PARTICIPANTS: Sixty eyes of thirty diabetic patients and sixty eyes of thirty healthy nondiabetic subjects were studied. INTERVENTION: Corneal thickness was measured by ultrasonic pachymeter. Corneal endothelial morphology was examined with a contact specular microscope. MAIN OUTCOME MEASURES: Corneal endothelial cell density, mean,cell area, coefficient of variation, percentages of hexagonal cells, and corneal thickness were measured. RESULTS: There was statistically significant increased corneal endothelial cell density and decreased mean endothelial cell area in the diabetic patients. The diabetic corneas had an increased coefficient of variation of endothelial cell area, a decreased percentage of hexagonal endothelial cell and an increased corneal thickness compared with the control subjects, but these differences were not statistically significant. The duration of diabetes mellitus was significantly correlated with pleomorphism, polymegathism and corneal thickness. Severity of diabetic retinopathy was correlated with endothelial cell density, but these correlations were low. The corneal changes were not correlated with glycemic control. CONCLUSIONS: The diabetic corneas tended to be thicker and had more pleomorphism and polymegathism, though this was not statistically significant. Duration of diabetes mellitus correlated significantly with these corneal changes. This suggests that corneal changes should be evaluated and confirmed before intraocular surgery in chronic diabetic patients.

Adult↗
PubMed2002

Comparison of quantitative histomorphometry and DNA ploidy in tissue sections of prostate carcinoma.

OBJECTIVE: To examine the ability of quantitative histomorphometry to predict DNA ploidy of prostate carcinoma in biopsy tissue sections assigned after quantitation by nuclear digital image analysis. STUDY DESIGN: Thirty-five diploid, 35 tetraploid and 35 aneuploid prostatic carcinomas in biopsies, assessed by the CAS 200 image analyzer (Bacus Laboratories, Lombard, Illinois, U.S.A.), were reevaluated by the Bacus Laboratories Incorporated Slide Scanner, a microscope that quantifies histologic images. Thirty-one histomorphometric features from cancer cells were captured at 40 x magnification, averaged across tilesfor each case and incorporated into a multivariate discriminant model to determine which features predicted ploidy interpretation by nuclear image analysis using the CAS 200. RESULTS: On average, 60 and 15 minutes were required to perform nuclear image analysis and histomorphometry, respectively. The multivariate discriminant model identified configurable run length, difference variance, contrast, inverse difference moment, sum entropy and diagonal variance as histomorphometry features capable of distinguishing diploid from nondiploid tumors (P < .05). Cross-validation studies showed the model correctly classified 74.3% of the diploid and 57.1% of the nondiploid cases. CONCLUSION: Quantitative histomorphometry can predict the ploidy of prostate carcinoma in biopsy tissue sections. Quantitative histomorphometry has potential as a method of rapidly assessing DNA ploidy otherwise earmarked for nuclear image analysis, resulting in savings of time and expense.

Adenocarcinoma↗