The puzzle of prostatic carcinoma.
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DNA, Neoplasm↗
Biomedical subjects
L G Koss
Publications and source records attributed to L G Koss.
Condylomata acuminata of the urinary bladder. Natural history, viral typing, and DNA content.
Three patients with condylomata acuminata of the urinary bladder are reported. Two of the patients were immunosuppressed, and one had longstanding extensive condylomata acuminata of the external genitalia and adjacent areas. All lesions recurred at least once and were difficult to treat. The diagnosis was confirmed by in situ hybridization on archival material with human papillomavirus (HPV) DNA probes under stringent conditions. In two of the patients, probes for HPV types 6 and 11 were positive; HPV 11 only was identified in one patient. Probes for HPV types 16 and 18 and pBR322 vector controls were negative. In one patient with a strong hybridization signal, the lesion was also positive for common papillomavirus antigen. DNA content measured by cytophotometry of Feulgen-stained whole nuclei isolated from lesions in two patients revealed a markedly aneuploid DNA pattern. Whether this is a factor in the behavior of the lesions is not known at this time. Although rare, HPV infection of the urinary bladder may result in widespread condylomatosis and may mimic giant condylomas of Buschke-Löwenstein or even verrucous carcinomas, sometimes necessitating radical treatment. Nevertheless, until there is proof to the contrary, the lesions must be considered benign and should not be confused with squamous cancer of the bladder.
Adult↗
Precursor lesions of invasive bladder cancer.
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Humans↗
The place of colposcopy and related systems in gynecologic practice and research.
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Cervix Uteri↗
An expert system designed as a tutoring tool in cervical cytology: TTCC-1 system.
A knowledge-based intelligent system being developed as a computer-assisted tutoring tool that can be used by teachers and students of cervical cytology is described. This system uses a combination of frames and rules as knowledge representation. Combination data structures called "prototypes" characterize the typical cytoplasmic and nuclear features of classes of cervical cells by using a specific prototype for each hypothesized cell type. A hypothesis-directed approach is used for problem solving. Rules are associated with each prototype or hypothesis. There are two major kinds of rules: deducing rules, used for deducing certainty factors (expressed as degrees of certainty of the hypotheses), and strategy rules, used for guiding the user in reaching a conclusion about the test cell. With an easy-to-use interactive menu, the user inputs a series of sets of qualitative cell features, which the system utilizes at various inference stages and finally arrives at a decision about the cell type.
Cell Biology↗
Aspiration biopsy--a tool in surgical pathology.
A historical overview of the origins of the thin needle aspiration biopsy is given. Current applications of this technique to palpable lesions and lesions requiring various forms of imaging techniques are briefly summarized. The principal advantages of this method of diagnosis are its rapidity, versatility, and applicability to patients with palpable lesions as an office procedure. The procedure is nearly painless, hence readily accepted, and often shortens the anxious wait for a diagnosis. In competent hands, given an adequate sample, the diagnosis can be rendered with an accuracy approaching that of a frozen section. In many instances of intrathoracic and intraabdominal space-occupying lesions, exploratory thoracotomies and laparotomies can be avoided, thus reducing significantly the time of hospitalization. The procedure is safe. Seeding of cancer along the needle track has been reported in a few instances, but the risk of this event must be considered extremely low. Thin needle biopsy may offer the patient an opportunity to participate in therapeutic decisions, for example, in women with breast cancer. Finally, the aspirated sample offers a number of research options that may lead to a better assessment of prognostic parameters and response to treatment in cancer.
Abdomen↗
Deoxyribonucleic acid ploidy and cell cycle events in benign colonic epithelium peripheral to carcinoma.
DNA ploidy and cell cycle phases of benign human colonic epithelium peripheral to adenocarcinoma were analyzed by flow cytometry in 188 prospective cases. Human colonic epithelium was shown to be diploid with a mean DNA index (DI) of 1.01. The G0G1 compartment accounted for nearly 93% of the cells with the remainder in the S and G2+M phases. Parallel [3H]thymidine uptake on selected cases confirmed the relatively low proliferative activity of colonic mucosa. The DNA index and the cell cycle compartments exhibited no correlation to the ploidy, Dukes' stage, size, and anatomical location of the corresponding malignant tumors. Approximately 25% of the benign samples possessed DI values outside of the diploid range (defined as the mean +/- sd). Analysis of these apparently hypo- (less than 0.92) and hyper- (greater than 1.09) diploid, histologically normal samples in terms of cell cycle kinetics and their relationship to Dukes' stage, location, distance, and the ploidy of the tumor showed no correlation. The only characteristic differentiating these "aberrant" samples from diploid benign tissue was variation in DI possibly due to differences in fluorochrome binding or accessibility to DNA. Whereas these results indicate some degree of variability in the DNA content of benign colonic epithelia, neither DI nor cell cycle kinetics appear to be affected by the presence of a malignant tumor and are not representative of either the ploidy or pathologic stage of the corresponding colonic carcinoma.
Adenocarcinoma↗
ras oncogene p21 as a tumor marker in the cytodiagnosis of gastric and colonic carcinomas.
This study was undertaken to determine whether the expression of ras oncogene product p21 can be used as a tumor cell marker of gastric and colonic carcinoma in brush smears. To detect p21 an immunocytochemical assay with RAP-5 monoclonal antibody was used. Benign epithelial gastric cells obtained from normal gastric mucosa or benign gastric lesions reacted negatively in 12 out of 13 cases. Similarly, benign epithelial colonic cells from normal colon or benign colonic lesions were negative for p21 in nine out of ten cases. Weakly positive reaction, confined to a few cell clusters only, was observed in one smear of a benign gastric ulcer and one smear of chronic ulcerative colitis. All 20 smears from colonic carcinoma and all 20 smears of gastric carcinoma contained cells that stained positively for p21, and the degree of tumor differentiation had no impact on the staining pattern. The results recorded in this study show that the immunocytochemical assay for the ras oncogene product may prove to represent a new tool for the cytodiagnosis of gastric and colonic carcinomas.
Antibodies, Monoclonal↗
Cytologic and histologic manifestations of human papillomavirus infection of the female genital tract and their clinical significance.
The historical developments in the recognition of the role of human papillomavirus (HPV) infection in cells and tissues of the female genital tract are briefly summarized. The identification of a specific marker cell, the koilocyte, has led to initial studies of frequency and biologic significance of neoplastic lesions of the uterine cervix associated with HPV. By molecular virology techniques, over 40 types of HPV have been identified and their tissue affinity determined. Types 6, 11, 16, 18, and 31 are most commonly associated with anogenital lesions, among them a broad spectrum of cervical intraepithelial neoplasia (CIN). While current evidence suggests that lesions associated with HPV Types 6 and 11 are potentially less harmful to the patient than lesions associated with HPV Types 16 and 18 (which have been identified also in invasive cervical carcinomas and cell lines derived therefrom), a major long term prospective study may be required to confirm this view. A factor that complicates the issue still further is the recent observation that HPV DNA of all four types has been identified in 11% of women and 5.5% of men free of disease. Infection with multiple viral types (including Types 16 and 18) was common in this apparently healthy population. Although HPV must be considered as a prime candidate for a transforming virus, current evidence suggests that the infection with the virus is per se an insufficient condition for the development of precancerous lesions or cancer of the uterine cervix and that another factor or factors may be necessary for these events to take place. Some of these possible cofactors such as age, repeated infections, and the immune status of the patient are discussed. A great deal of additional work is required before the precise role of HPV virus in the genesis of carcinoma of the uterine cervix, vulva, and vagina is firmly documented.
Adult↗
Modification of Ha-ras oncogene p21 expression and cell cycle progression in the human colonic cancer cell line HT-29.
Multiparameter flow cytometric measurements of the Ha-ras oncogene product, Ha-p21, versus DNA content were used to study the effect of prednisolone, sodium butyrate, and hyperosmolality on the expression of this gene during the cell cycle of HT-29, a human colonic carcinoma cell line. In control cells the expression of Ha-p21 was cell cycle dependent; it increased during G1 and remained approximately constant as cells traversed the S- and G2 + M phases. Two compartments of G1 cells, one expressing low (G1A) and the other (G1B) high levels of Ha-p21 could be identified. Cells grown with prednisolone (1.4-2.1 microM) expressed higher Ha-p21 levels than controls. Cell cycle analysis revealed that this effect was accompanied by a change in the distribution of cells in G1 phase: whereas the proportion of cells in G1A was reduced, that of cells in G1B was increased. The steroid had no detectable effect on cells in S and G2 + M. By contrast, sodium butyrate and hyperosmolality caused a marked decrease in Ha-p21 content. This reduction was not accompanied by any modification of the proportion of cells in the cell cycle compartments. These results would suggest that Ha-p21 is not likely to be a primary regulator of cell cycle progression in HT-29 cells.
Butyrates↗
Flow cytometry and Feulgen cytophotometry in evaluation of effusions.
Fifty-eight effusions (42 pleural and 16 ascitic fluids) from patients with and without cancer were analyzed by conventional cytology and the results compared with DNA patterns generated by flow cytometry of 10(4) nuclei and several modes of Feulgen cytophotometry. In 31 patients (24 without evidence of cancer and seven with history of cancer and cytologically negative fluids), the fluids were diploid by flow cytometry. One fluid with atypical cells from a lymphoma suspect was also diploid. Flow cytometry of 26 cytologically cancerous fluids disclosed aneuploid DNA patterns in 16 and diploid patterns in ten. Feulgen cytophotometry of 11 of these fluids (three aneuploid, eight diploid) was performed on nuclear preparations identical to those used in flow cytometry and on restrained smears used for visual analysis. The analysis was performed in two modes: as a study of 500 sequential nuclei in an automated system, mimicking flow cytometry, and visually selected large, presumably malignant nuclei. In nine of the 11 cases, the DNA content of visually selected cancer cells was aneuploid, even though this DNA pattern was not evident in the analysis of 500 sequential cells. In two cases, both diploid by flow cytometry, the Feulgen analysis confirmed the presence of cancer cells in the diploid range. In samples of 10(4) nuclei representing a mixed population of cells occurring in effusions, the presence of aneuploid cancer cells may not be disclosed by conventional flow cytometry. A larger sample of cells, a detailed analysis of DNA histograms, and perhaps sorting of select cells in the hypertetraploid range, may prove essential before flow cytometry can be accepted as a diagnostic tool in the laboratory in the assessment of effusions.
Aneuploidy↗
DNA distribution patterns in early gastric carcinomas. A Feulgen cytometric study of gastric brush smears.
DNA distribution patterns were studied by cytophotometry in 20 Feulgen-stained brush smears of early gastric carcinomas. Two different DNA distribution patterns, classified as predominantly diploid and aneuploid, were correlated with histologic data. Six of seven carcinomas of diffuse type were predominantly diploid. By contrast, 11 of 13 intestinal type carcinomas were aneuploid and two were diploid. Since the DNA distribution patterns recorded in this study were previously observed in advanced gastric carcinomas, this would suggest that the basic genetic make-up of the tumors does not change with tumor progression.
Adult↗
Identification of human papillomavirus types in male urethral condylomata acuminata by in situ hybridization.
An in situ hybridization technique was applied under stringent conditions to paraffin sections of urethral condylomata from male patients to determine the presence of DNA sequences of human papillomavirus (HPV) types 6, 11, 16, and 18. The material consisted of 15 classical condylomata acuminata, two flat condylomata, and five recurrent lesions. HPV DNA sequences could be identified in all 15 condylomata acuminata; in 13 lesions, two types of viral DNA were observed (types 6 and 11 in 12, types 6 and 18 in one). In the remaining two condylomata acuminata, only HPV type 11 was present. One of the two flat condylomata was negative with all the probes, and one was borderline-positive for HPV 6. Four of five recurrent lesions contained the same types of viral DNA as the primary lesions, albeit with slight differences in the intensity of viral expression. One lesion was negative with all probes. We conclude that urethral condylomata in males contain the same types of HPV as seen in other anogenital lesions of both sexes and that infection with two viral types is common. In situ hybridization with HPV DNA probes is applicable to archival material and therefore may prove to be of value in future epidemiologic studies comparing lesions in sexual partners. The determination of viral type may have therapeutic implications.
Adolescent↗
Characterization of human papilloma virus types in condylomata acuminata in children by in situ hybridization.
The presence of human papilloma virus (HPV) DNA sequences of types 6, 11, 16, and 18 was determined by in situ hybridization under stringent conditions on archival paraffin-embedded tissue sections in eight condylomata acuminata observed in children below the age of 12 years. Viral sequences were detected in seven of eight cases: all of them contained HPV 6, four contained also HPV 11, and one contained HPV 16 and 18. Papilloma virus common antigen was detected in only three of eight cases, all of them being positive also by in situ hybridization. We conclude that most condylomata acuminata in children are associated with the same types found in anogenital lesions in adults. Since little is known about the long-term significance of genital condylomas in children the identification of the papilloma virus type may prove to be important as a prognostic tool particularly in patients infected with HPV types 16 and 18, thought to have high oncogenic potential.
Antigens, Viral↗
Current concepts of intraepithelial neoplasia in the uterine cervix (CIN).
The unifying concept of precancerous events in the epithelia of the uterine cervix is reviewed in the light of epidemiologic and morphologic observations. The role of human papillomavirus (HPV) infection as a factor in the genesis of precancerous states and carcinoma of the uterine cervix is assessed. Although cytologic, histologic, ultrastructural and molecular biologic data support the concept of HPV as an oncogenic virus, the precise mechanisms linking the infection with cancer are not known at this time. A hypothesis of the presumed sequence of events is presented.
Carcinoma↗
Automated cytology and histology, A historical perspective.
The current status of the techniques of image analysis, morphometry and DNA measurements of human cells and tissue samples is reviewed, and the goals of these various techniques, in terms of the detection, diagnosis and prognosis of human cancer, are briefly summarized. Some of the accomplishments and problems of this research are discussed, and targets of future investigations are proposed. It is quite evident that the full value of objective assessment of human cells has not yet been achieved and that many years of additional research may be required to evaluate fully their significance as a scientific tool of objective diagnostic and prognostic value.
Cytological Techniques↗
DNA cytophotometry of voided urine sediment. Comparison with results of cytologic diagnosis and image analysis.
Measurements of nuclear DNA were performed in urothelial cells in 54 Feulgen-restained cytocentrifuge preparations of voided urine previously studied visually and with an image analysis system. The study included 30 patients with bladder tumors of various grades, 9 patients with prostatic disease and 15 control samples from normal donors. A number of additional control measurements were performed, including measurements in tissue samples of the 30 bladder tumors corresponding to the cytologic samples. It was documented that DNA can be measured in most urinary sediments. The diagnostic performance of the image analysis system reflected the DNA patterns in 47 of the 54 cases. In several instances, particularly in cases of prostatic disease, the image analysis system recognized abnormal DNA patterns in the absence of significant morphologic abnormalities in the urothelial cells. In seven cases, the image analysis findings failed to conform with the DNA patterns. The reasons for these surprising results are discussed, and future modifications of the image analysis system are proposed.
Aged↗
Expression of Ha-ras oncogene p21 protein in relation to the cell cycle of cultured human tumor cells.
It has been postulated that the expression of the product (p21) encoded by the ras genes may have a role in cell cycle events. Simultaneous multiparameter flow cytometry was used to measure the p21 content in relation to the cell cycle of several cancer cell lines of human origin. These studies revealed that p21 levels rise during the G1 phase of the cycle and remain approximately constant as cells traverse the S and G2 + M phases. The threshold level of p21 expression of S phase cells was used to divide the G1 cell population into cells with low (G1A) and high (G1B) p21 content. The p21 levels of G1B cells were approximately ten times higher than those of G1A cells. The validity of this subdivision was confirmed by synchronous measurements of RNA content and p21. Cells with low RNA content, hence in early part of G1 phase of the cell cycle, expressed low levels of p21, and cells with higher RNA content expressed higher levels of p21. These observations suggest that the levels of p21 are much lower at the onset of the cell cycle than at its end; hence a drop in p21 expression is likely to occur during or immediately after mitotic division.
Cell Cycle↗