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B Stenkvist

Publications and source records attributed to B Stenkvist.

At least 19 recordsLinked to original sources

Appearance and detection of multiple copies of the mdr-1 gene in clinical samples of mammary carcinoma.

To examine the presence of multiple copies of the mdr-I gene in clinical tumor samples we have developed an approach where the cells are obtained by fine-needle biopsies and the number of gene copies determined by PCR. The temporal appearance of amplified mdr-I was examined in 20 breast-cancer patients with clinical stage-IV disease receiving endocrine treatment. Tumor samples were obtained every 2nd to 3rd month from the same tumor lesion. None of the initial samples from each patient contained multiple copies of mdr-I. Of 16 patients who showed increased tumor size, 4 developed multiple gene copies, showing that the event occurs without cytotoxic selection of cells with chemotherapy.

Aged

Detection and temporal appearance of multiple copies of c-erb-B2 genes in advanced mammary carcinoma using fine needle biopsies and the polymerase chain reaction.

Aspiration of tumor cells by the fine-needle biopsy method yields only a small number of cells, which hampers conventional molecular analysis for the presence of multiple copies of oncogenes. We have therefore adopted the polymerase chain reaction (PCR) method to study semi-quantitatively the level of the c-erb-B2 gene in human breast tumor samples. Of 39 patients with mammary carcinoma, 7 (19%) contained multiple copies of c-erb-B2 genes, whereas only two samples failed to give informative data. Next the multiple copies of c-erb-B2 genes, whereas only two samples failed to give informative data. Next the temporal appearance of multiple gene copies was examined in 20 patients with clinical stage IV disease. Tumor samples were obtained every second to third month from the same tumor lesion of each patient. None of the initial samples from each patient contained multiple copies of c-erb-B2. Of 16 patients that showed progressive clinical disease, 5 developed multiple gene copies, showing that the event occurs in clinical stage IV disease.

Aged

Amplification of oncogenes in mammary carcinoma shown by fine-needle biopsy.

A procedure that measures the amplification of oncogenes in human cancer cells is described. The cells were obtained by fine-needle biopsy to allow repeated sampling from individual metastases. A drawback was the low number of cells obtained, but this could be overcome by using a slot-blot hybridization technique to measure gene amplification. Two patients with mammary cancer (primary tumors or metastases), analyzed for the levels of amplification of the oncogene erb-B2, are described in detail. This technique is suitable for analyzing alterations occurring during cancer progression and for identifying subgroups of mammary cancer with different characteristics.

Aged

Image analysis cytology for DNA determination in breast and prostate cancer.

Nuclear DNA distribution in fine-needle specimens from 112 breast carcinomas and 45 prostatic tumours was studied. The distributions were described statistically with five separate descriptors, namely mean deviation from 2C, percentage of cells exceeding 2.25C and 4.5C respectively, DNA index and entropy (a mathematical measure of degree of scatter of the DNA content of the nuclei). It was shown that information about DNA index only ('diploid' versus 'aneuploid') is too limited and the term 'diploid' even incorrect and misleading for description of human cancer cell populations. Merely an addition of the percentage of cells exceeding 2.25C allowed separation of a majority of the carcinoma specimens from specimens taken from normal tissue. Moreover, in carcinoma specimens 96% of the patients had between 1 and 100% of the cancer nuclei cell population exceeding 4.5C in contrast to all normal specimens, where this percentage was 0. Entropy was clearly correlated with percentage of Ki-67-positive cells, indicating that it contains information on both scatter of nuclear DNA content and proliferation. Plotting of the scatter (entropy) versus DNA index allowed separation of greater than 97% of the carcinoma specimens from specimens taken from normal individuals. With the use of all five descriptors of DNA distribution it was possible to separate all breast cancer specimens and all moderately and poorly differentiated prostate cancer specimens from normal specimens. The discrimination between well-differentiated prostate cancer and hyperplasia constituted a special problem in that it was not possible to confirm the diagnosis well-differentiated prostate cancer by objective measurements in 8% of the patients, even when all five descriptors were used for the analysis. None of the verified carcinoma specimens had a DNA distribution that was truly 'diploid' in the sense of the distributions of cancer nuclei and normal cell nuclei from the actual organ being quite similar.

Biopsy, Needle

Cytological and DNA characteristics of hyperplasia/inflammation and cancer of the prostate.

A study has been made of the correlation between objectively measured nuclear DNA content (by image analysis cytometry) and visual pathologic/cytologic diagnoses in hyperplasia/inflammation and well, moderately and poorly differentiated carcinomas of the prostate. The DNA measurement data were described by four statistical description methods--namely mean deviation from 2C, percentage greater than 4.25 C, DNA index and entropy. In 36% (5/14) of well differentiated and 13% (1/8) of moderately differentiated cancer it was not possible by objective measurement methods to demonstrate any difference between hyperplasia/inflammation and cancer. On the other hand one or more of the statistical descriptors was significantly different from hyperplasia/inflammation in all of those cancers visually diagnosed as poorly differentiated. The results underline the need for improvement of diagnostic criteria of prostate cancer--in particular well differentiated--in order to correctly understand the epidemiology (true incidence), survival and effects of treatment on the disease.

DNA

Entropy as an algorithm for the statistical description of DNA cytometric data obtained by image analysis microscopy.

In an effort to obtain an additional statistical descriptor of DNA histograms we analysed a concept from mathematical information theory, called entropy, which describes the information content of histograms irrespective of parametric or non-parametric distributions. For this study, 32 fine-needle biopsies were analysed. It seems that the entropy of the DNA histogram is an extremely useful descriptor for the separation of distributions obtained from malignant tumours when compared with non-malignant lesions or normal controls.

Algorithms

DNA determination in endometrial carcinoma by flow and image cytometry.

Endometrial carcinomas from 29 patients were analyzed by flow and image cytometric techniques with respect to DNA-content. Good agreement of ploidy value was obtained in 22 of the cases. A correlation was demonstrated between percentage cells above 2.5 C in image cytometry and S-phase as determined by flow cytometry. The interpretation was that cells with major chromosomal abnormalities may also have a high proliferative rate. These two features cannot be separated by image cytometry, whereas this is claimed to be the case according to the terminology used in interpretation of flow cytometric data. Our findings underline the need for a clarification of the terminology used in cell measurements on clinical material as well as proper choice of cytometric method to be used in conjunction with diagnostic cytology. The possible clinical value of the descriptors chosen from the two methods awaits follow-up of the patients.

DNA, Neoplasm

Cytophotometric estimation of cell proliferation in breast cancer. Correlation to the clinical course during long-term follow-up.

Tumours from 117 patients with breast cancer operated during a 5-month period 1975-1976 were investigated by absorbance scanning cytophotometry. The relations of these data to breast cancer recurrence and death during a follow-up period of 8.5 years were analysed using Cox's proportional hazards model. When individually tested, nodal status, grade of malignancy and high rates of proliferation, as indicated by cells in S-phase, were statistically significant predictors of the clinical outcome. The risk ratio associated with S-phase decreased significantly over time from primary treatment. No significant relation was found between DNA-ploidy or tumour size and the clinical course. In the multivariate analysis, based on 76 patients, nodal status alone was a significant prognostic factor.

Adult

Analysis of machine-selected cells with an image analysis system in normal and abnormal cervical specimens.

An analysis has been performed of visual diagnostic criteria used in cervical cytology applied to machine selected cells in relation to automated classification based on variables, which can be recorded in an image system with automated cell search and segmentation, feature extraction and classification. A 98% accuracy could be obtained with the choice of the most ideal statistical methods for discrimination and the use of the most powerful variables recorded in the image system when compared with consensus of the visual diagnoses based on established cytological criteria for diagnosis of cancer and precancer of the cervix uteri. The most powerful discriminatory variables in the image system (of 17 recorded) for discrimination between normal and abnormal epithelial cells were, in addition to nuclear extinction, cytoplasmic extinction and cytoplasmic shape. It is concluded that the visual classification of cervical cells is highly accurate with experienced observers and that imaging microscopes can be trained to nearly equal this accuracy with appropriate statistical methods of discrimination. The problem of creating fully automated systems, however, also requires the inclusion of even more effective discriminatory variables and also the solution of such problems as automatic cell search, segmentation, artifact rejection, feature extraction, classification and electronic stability in order to become cost-effective.

Cervix Uteri

Automatic analysis of Papanicolaou smears by digital image processing.

Papanicolaou smears from 378 patients were analyzed in a fully automated microscope system using an image analysis technique. The logic of the system subdivided the smears into "normal" (63%), "not possible to analyze in the machine" (17%) and "positive" (20%). The results have been compared with the conventional screening method available today taking into consideration the definition problems of a true diagnosis, cytopathological and histopathological consensus, reproducibility, sample-taking and interpretation mistakes, etc. As 37% (rejected and positive) of the smears in this particular study were analyzed visually after machine prescreening, it could be demonstrated that the false-negative rate among the remaining 63% of the specimens was significantly lower among the machine-screened smears when compared with visual screening if the results were correlated with histopathological consensus. The results clearly indicate that the technology required to build computerized microscope systems, which are able to automatically sort out at least two thirds of Papanicolaou smears is available today. The only limiting factor is the cost-benefit relationship.

False Negative Reactions

Nuclear DNA content in squamous cell carcinoma, small cell carcinoma, and bronchiolo-alveolar carcinoma of the lung.

Nuclear DNA content in individual, morphologically identified tumor cells from 33 squamous lung carcinomas, 20 small cell lung carcinomas, and 10 bronchiolo-alveolar carcinomas were analyzed by means of cytophotometry on Feulgen-stained histologic and cytologic specimens. Twenty-eight of the squamous cell carcinomas and 17 of the small cell carcinomas had high and scattered DNA values, indicative of high malignancy potentials. None of the bronchiolo-alveolar carcinomas showed such high DNA values. These results are in line with clinical experience that squamous cell and small cell carcinoma are associated with rapid progression and death in patients, whereas bronchiolo-alveolar carcinomas have a more indolent course.

Adenocarcinoma, Bronchiolo-Alveolar

Image cytometry in malignancy grading of breast cancer. Results in a prospective study with seven years of follow-up.

A fully automated system for image cytometry is presented. In combination with a special tumor sampling procedure, the system proved able to record with high reproducibility a large number of tumor cell population descriptors of high prognostic significance in a prospective study of breast cancer. These included the degree of abnormality of DNA distribution (strongly correlated with the proliferative rate) and some descriptors of shape and texture (strongly correlated with the grading system for breast cancer suggested by the World Health Organization). While the extreme complexity of a true malignancy grading system for breast cancer is underlined, the results of this study indicate that its creation is a possibility, given sufficient effort by interdisciplinary teams using modern sophisticated analytical techniques.

Breast Neoplasms

A program for logistic prediction modelling.

A computer program has been developed that can be used for analysing a binary outcome variable and a set of regressors of type interval with a logistic (i.e. nonlinear) model.

Biometry

Fine-needle biopsies of renal transplants in clinical rejection monitoring.

Fine-needle aspiration biopsy( FNAB) of renal allograft transplants has been used at Uppsala University Hospital for 3 years. Experience from 51 consecutive patients (from 1 1/2 years) with 333 FNAB was reviewed. Representative material was obtained in more than 70% of the biopsies. Eleven rejection episodes in 12 patients were confirmed with this method. One was not recognized. Significant inflammation in the kidney without clinical rejection was found in 22 patients. The possible causes of such inflammation are discussed. Repeatedly recorded inflammation in the kidney with minor or no effect on graft function may sometimes be caused by viral infection. The clinical value of FNAB in various immunosuppressive regimens is discussed.

Azathioprine

Papanicolaou smear screening and cervical cancer. What can you expect?

More than 90% of the total female population of three Swedish counties between the ages of 30 and 59 years, 53% of women between 60 and 69 years, and 25% of women older than 70 years were screened for cervical cancer with the Papanicolaou smear over a ten-year period. The uniqueness of the study is that in Sweden it is possible to follow up the entire population during their lifetimes via a population register, which has its roots in the 17th century, natural to Swedes but almost incomprehensible in the United States or United Kingdom. Every Papanicolaou smear taken was computer recorded and linked on an individual level to the cancer registry. There were 207,455 women followed up for ten years. No women were lost to follow-up. There was a 75% decrease in invasive cervical cancer incidence among women who had smears taken at least once during the ten-year period. Among those women who had never had smears taken, the incidence of invasive cervical cancer was four times as great as among those women who had been examined at least once. We estimate that the system proposed by Swedish Medical Board (at least one smear every three years) for cervical cancer screening can reduce the incidence of invasive cervical cancer to a level between one and five cases per 100,000 women per year in a completely screened population.

Adult