Search PubMedSearch

Biomedical subjects

G L Wied

Publications and source records attributed to G L Wied.

At least 19 recordsLinked to original sources

Comparison of estrogen receptor immunocytochemical assay in frozen and paraffin sections.

Frozen and paraffin sections of 11 breast carcinomas were stained for estrogen receptors (ER) using the same rat monoclonal primary antibody, D75P3, as the marker and alkaline phosphatase as the chromogen-linking enzyme. The results of this staining process were assessed visually and with the microTICAS image analysis system to determine the degree of correlation between frozen and paraffin-embedded tissue. In all specimens, some fraction of the nuclei stained positively. This included two specimens selected for their biochemically negative assay; one of them stained strongly positively with D75P3. The results of quantitative analysis support the visually apparent correlation between the two types of samples in terms of both overall staining pattern and intensity of nuclear staining. Although the conclusions of this pilot study are limited because of the small number of cases, this method of staining establishes the feasibility of representative ER determination in archival paraffin-processed material. The additional information provided by this method is potentially useful in stratifying patients in prospective studies on the basis of the efficacy of hormonal therapy in biochemically ER positive breast tumors.

Antibodies, Monoclonal

Image analysis cytometry of dysplastic nevi.

Computerized image analysis was used to assess nuclear atypia in 24 dysplastic nevi (DN), 19 CN (CN), and five thin melanomas. DN were selected for the study using architectural criteria alone. Feulgen-stained, 6-um sections were analyzed with a microTICAS cytometer. At least 100 nuclei were measured in each case. The standard deviation of nuclear area, mean nuclear roundness, standard deviation of nuclear roundness, mean ploidy, and standard deviation of ploidy were found to be significantly greater for DN than for CN. DNA histograms from DN showed an increased fraction above 2N, suggesting that DN are more proliferative than CN. No DN were aneuploid. All melanomas were aneuploid, and differed significantly from DN in mean nuclear area, standard deviation of nuclear area, mean ploidy, and standard deviation of ploidy. There were no significant differences between the junctional and intradermal populations of compound DN in any of the measured parameters, except that the intradermal nuclei were significantly rounder than the junctional nuclei. There were no significant differences between DN from patients with only a single DN and DN from patients with at least two dysplastic nevi.

Cell Nucleus

Artificial neural networks and their use in quantitative pathology.

A brief general introduction to artificial neural networks is presented, examining in detail the structure and operation of a prototype net developed for the solution of a simple pattern recognition problem in quantitative pathology. The process by which a neural network learns through example and gradually embodies its knowledge as a distributed representation is discussed, using this example. The application of neurocomputer technology to problems in quantitative pathology is explored, using real-world and illustrative examples. Included are examples of the use of artificial neural networks for pattern recognition, database analysis and machine vision. In the context of these examples, characteristics of neural nets, such as their ability to tolerate ambiguous, noisy and spurious data and spontaneously generalize from known examples to handle unfamiliar cases, are examined. Finally, the strengths and deficiencies of a connectionist approach are compared to those of traditional symbolic expert system methodology. It is concluded that artificial neural networks, used in conjunction with other nonalgorithmic artificial intelligence techniques and traditional algorithmic processing, may provide useful software engineering tools for the development of systems in quantitative pathology.

Artificial Intelligence

Artificial intelligence-guided analysis of cytologic data.

A design for the integration of artificial intelligence (AI) technology with large databases of clinical and objective cytologic data, such as are on file at the University of Chicago, is presented. Among the key features of this approach are the use of a knowledge representation structure based upon an associative network, the use of a Bayesian belief network as a method of managing uncertainty in the system, and the use of neural networks and unsupervised learning algorithms as a means of discovering patterns within this database. Such an automated approach is necessary, given the complexity and interdependence of these data, to gain an understanding of their dependence structure and to assist in their exploration and analysis.

Algorithms

DNA ploidy profiles as prognostic indicators in CIN lesions.

The prognostic significance of DNA ploidy measurements in cervical tissues was examined. Microphotometric measurements of 302 Feulgen-stained tissue sections (91 normal squamous epithelia, 14 condylomata, 29 cervical intraepithelial neoplasia (CIN) I, 78 CIN II, and 90 CIN III) were performed with a personal computer (PC)-based video microphotometry system. Analysis of these data shows that the DNA profile provides significant prognostic information: CINs with a polyploid DNA profile are more likely to return to normal than are those exhibiting an aneuploid pattern. Of 211 abnormal cases, 38% had polyploid DNA profiles and 62% were aneuploid. Eight-six percent of the cases that regressed were polyploid and 14% were aneuploid. Of the 130 aneuploid DNA cases, 95% remained static or progressed and only 5% regressed. Of these nonregressing aneuploid lesions, 90 remained static and 34 progressed, whereas within the nonregressing polyploid group 37 remained static and only 6 progressed. This result holds across diagnostic categories. Several other ploidy-related descriptors also showed prognostic significance (including mean ploidy, the 5N exceeding rate and 2N deviation index, and discriminant functions derived from order statistic analysis of the cumulative DNA histograms), but not to the degree or with the consistency of expression as the DNA profile categorization. These results indicate that important information about the prognosis of CIN lesions may be obtained by the DNA profile on Feulgen-stained tissue specimens. The data were acquired by a cytophotometry system of relatively modest cost consisting of readily available hardware components.

Aneuploidy

The significance of DNA measurements in a histologically defined subset of infiltrating ductal carcinomas of the breast with long-term follow-up.

The nuclear DNA content and other karyometric parameters were evaluated in a histologically homogeneous group of invasive ductal carcinomas of the breast from 13 patients who survived 25 years after radical mastectomy and from 13 controls matched for histologic tumor grade, lymph node status, tumor size and patient age. The nuclear DNA content and other morphometric features were evaluated by image analysis (using a modified TICAS system) on 12-microns-thick, Feulgen-stained sections. The DNA content of the tumors of both the long-term survivors and the controls varied from the diploid range to highly aneuploid (with a large proportion of the cells having a DNA content above 5N). Overall, the tumors of the controls exhibited a higher ploidy, a greater deviation from the diploid range and a greater variation of nuclear size than did the tumors of the long-term survivors. These results suggest that these measurements may be helpful in yielding prognostic information among sets of histologically identical breast tumors of similar pathologic stage.

Adult

Assessment of hormone receptors in breast carcinoma by immunocytochemistry and image analysis. I. Progesterone receptors.

Frozen sections of 30 breast carcinomas were stained for progesterone receptors (PRs) using a rat monoclonal primary antibody and an alkaline phosphatase-antialkaline phosphatase technique. The micro-TICAS image analysis system was used for evaluation of the staining, with the results obtained by image analysis compared with the results of biochemical assays for PR. Strong positive/negative concordance (90%) was observed between the immunohistochemical and biochemical assays. However, the numerical values of the positive cases in the two assays did not correlate well, possibly because the biochemical assay does not take tumor cellularity into account. Three PR distribution patterns, designated A, B and C, were identified by image analysis among the breast tumors. In the type A pattern, tumor cell nuclei were diffusely and uniformly labeled. In type B, both clearly negative as well as distinctly positive cells were present. In type C tumors, a broad range of labeling reactions (from negative to intensely positive) was observed. These results imply (1) that the PR content of human breast carcinoma may be accurately and objectively assessed by the image analysis of immunohistochemically stained frozen sections, (2) that image analysis may provide a more accurate estimate of the cellular content of PR than do biochemical assays and (3) that PR distribution patterns obtained through image analysis permit the consistent appraisal of intratumoral heterogeneity of PR expression, which is potentially of prognostic importance.

Breast Neoplasms

Assessment of hormone receptors in breast carcinoma by immunocytochemistry and image analysis. II. Estrogen receptors.

Frozen sections of 30 invasive breast carcinomas were stained for estrogen receptors (ERs) and the tumor cell proliferative rate by an immunoalkaline phosphatase technique. The stained sections were evaluated for ER by the microTICAS image analysis system. Seventeen tumors were ER positive and 13 were ER negative by image analysis. There was 93% concordance between the ER results obtained by image analysis and those obtained by biochemical methods. One case that was ER negative by image analysis was weakly positive by biochemical assay; a second case was ER positive by image analysis but ER negative by biochemical assay. Twelve of the 17 ER-positive tumors were diffusely positive while 5 displayed considerable intratumoral heterogeneity, with tumor cells exhibiting a broad range of intensity of receptor expression. In most cases, the image analysis ER status coincided with the progesterone receptor (PR) status, but in a large minority of cases (41%) the ER status and the PR status differed. Tumors with a high growth fraction (greater than 30%), as measured by Ki-67 immunostaining, were uniformly ER negative. The results of this investigation suggest that immunohistochemical staining of frozen sections for ER aided by automated image analysis (1) reliably detects the receptor in breast carcinoma, (2) allows for the assessment of heterogeneity within tumors and (3) may be used as part of a panel of antibodies to markers of potential prognostic importance in a single small tissue sample.

Breast Neoplasms

A nuclear DNA study of uterine cervical dysplasia with reference to its prognostic significance.

To further define the nuclear DNA content of uterine cervical dysplasia and its relationship to prognosis and epidemiological features, a retrospective study using Papanicolaou stained cytological specimen and TICAS was undertaken. 1. Dysplasia patients was common among young females who had a background of low age first pregnancy, multiple Gravidity-Parity, the complication of inflammation and the use of hormonal contraceptives and progressed rapidly. It is recommended that a test should be repeated within 2 to 3 months regardless of the severity of the dysplasia and patients should be followed up for at least 2.5 to 3 years. 2. The DNA histograms were classified into 3 types (A,B and C): Type C, which had the stem line in an aneuploidy area, showed more severe dysplastic cases. This may be due to the proliferation rate and significant alternation in the chromosomes and mitoses. Nuclear DNA analysis using TICAS and Papanicolaou stained cytological material could discriminate between the progressive group and the persistent or regressive group. In addition, the mean nuclear area might be the best indicator of prognosis in uterine cervical dysplasia.

Adolescent

DNA analysis cervical and vaginal cancer cells during radiotherapy by rapid high-resolution cytometry.

The DNA content of the nuclei of cancer cells of 12 cases of cervical cancer and 2 cases of vaginal cancer, treated with radiotherapy, were studied in 50 specimens. Specimens were taken from each case before radiotherapy and at the totals of 1,000 rad, 2,000 rad, 3,000 rad and 4,500 rad (or 5,000 rad). All specimens were stained by the Papanicolaou method and were analyzed by rapid high-resolution cytometry. Total optical density, mean nuclear area and the 5N-exceeding rate (5NER) increased gradually following irradiation. Cancer cells disappeared in good response cases before 3,000 rad. Eight smears with a 5NER under 100 at the dose of 3,000 rad or more seemed to be poor response cases. Low 5NER and low mean nuclear areas were observed in both patients who died with persistent disease after radiotherapy, as well as in one case treated with chemotherapy for persistent disease after radiotherapy.

Adult

Retrospective DNA analysis by rapid high resolution cytometry in cases with cervical cancer before and after radiotherapy.

DNA analyses of nuclei of squamous cells on 86 cases with squamous cells carcinoma of the uterine cervix, who had been treated with radiotherapy, were studied in 95 specimens. Forty-three specimens taken from invasive cancer cases before radiotherapy and 52 smears taken from the patients with cervical cancer after radiotherapy were examined by rapid high-resolution cytometry. The biologic behavior in this retrospective study was known, and the cases were classified into "poor" and "good" prognostic groups depending on their five year survival rates. In the poor prognostic group, the smears taken prior to radiotherapy showed a significantly lower 5N-exceeding rate (5NER) and a smaller Nuclear area than did those of the good prognostic group. The smears taken from the cases of recurrent cancer and postradiation dysplasia with poor prognosis showed significantly lower 5NER and a smaller Nuclear area than did those from cases of postradiation dysplasia and radiation changes in patients with a good prognosis after radiotherapy.

Adult

Nuclear DNA in anaplastic thyroid carcinoma with a differentiated component.

Fifteen cases of anaplastic thyroid carcinoma, including eight cases with a differentiated component, were studied by DNA analysis. All areas of anaplastic carcinoma showed an aneuploid DNA content. The eight cases of anaplastic carcinoma with differentiated component (two follicular carcinomas, two papillary carcinomas, one Hürthle cell carcinoma and three poorly differentiated carcinomas) exhibited aneuploid DNA content in the differentiated area of the tumour. Karyometric parameters allowed a fairly clear separation between giant cell, spindle cell and differentiated components. The results support the hypothesis that patients with aneuploid differentiated carcinoma represent a higher risk group and are probably more prone to developing anaplastic carcinoma.

Carcinoma

Human papillomavirus standardization and DNA cytophotometry in cervical intraepithelial neoplasia.

Human papillomavirus (HPV) standardization and DNA cytophotometry were carried out in 29 cases of cervical intraepithelial neoplasia (CIN) grades I-III. A prognostically unfavorable DNA distribution pattern with an aneuploid stemline was found in 14 of the 16 dysplasias with HPV types 16 and 18, while in 11 of 13 dysplasias with HPV types 6 and 11 there was a favorable DNA distribution with a euploid-polyploid stemline. Among 178 colposcopically, cytologically and histologically confirmed cervical lesions, there was a statistically significant incidence of HPV 16/18 infections in severe dysplasias and carcinomas, while HPV 6/11 was found predominantly in mild cervical lesions. It seems that CIN can be divided into high- and low-risk lesions not only by the degree of severity and the DNA distribution pattern but also by HPV typing.

Adult