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L G Koss

Publications and source records attributed to L G Koss.

At least 73 records · Page 4Linked to original sources
PubMed1989

Expression of ras oncogene p21 protein in early gastric carcinoma and adjacent gastric epithelia.

The expression of the ras gene product p21 in normal gastric mucosa, early gastric carcinoma of diffuse (gastric) and intestinal types, and in adjacent mucosal abnormalities is reported. The analysis was performed on paraffin sections by an immunohistochemical assay using the mouse monoclonal antibody RAP-5 and the rat monoclonal antibody Y13-259. Expression of ras p21 was assessed by staining intensity and percentage of positively stained cells. In comparison to normal gastric mucosa of non-cancer patients, p21 was overexpressed in nearly all early carcinomas of both types and in the dysplastic and/or metaplastic mucosal alterations accompanying intestinal type of gastric cancer. Increased p21 expression was also observed in the normal-appearing mucosa adjacent to early carcinomas of diffuse type, but not in the morphologically normal gastric epithelium adjacent to the intestinal type. The results of this investigation suggest that ras p21 overexpression may be related to early events of human gastric carcinogenesis. The study supports the notion of different pathways in the development of diffuse (gastric) and intestinal types of gastric carcinomas.

Adenocarcinoma↗
PubMed1989

Predictive value of DNA measurements in bladder washings. Comparison of flow cytometry, image cytophotometry, and cytology in patients with a past history of urothelial tumors.

Comparative DNA ploidy measurements were carried out by flow cytometry and by image analysis on cells in 71 bladder washing specimens from 50 patients with past histories of bladder tumors. Among the specimens classified as diploid or questionable by flow cytometry, 14 showed the presence of aneuploid DNA values documented by image analysis. In 18 of the 50 patients, recurrent tumors were observed during a relatively brief period of follow-up. In 15 of them the DNA pattern was aneuploid and in three it was questionable. In nine of the 15 patients, both methods of DNA analysis disclosed aneuploidy, but in six patients aneuploidy was detected by image analysis only. A combination of DNA aneuploidy, whether observed by flow cytometry, image analysis, or both, and of positive or suspicious urine cytology is highly predictive of recurrence of high grade bladder tumors. Image analysis of DNA content in bladder washings adds information of clinical value above and beyond that obtained by flow cytometry.

Aged↗
PubMed1989

Expression of ras oncogene p21 protein in relation to regional spread of human breast carcinomas.

The oncogenes most frequently detected in human tumors belong to the ras gene family (Ha-ras, Ki-ras, and N-ras). These genes encode a group of closely related 21,000 dalton proteins termed p21. An immunohistochemical study of ras p21 expression was carried out on paraffin sections of 54 human breast carcinomas using monoclonal antibodies to p21. The control group consisted of ten cases of benign fibrocystic disease. The p21 expression was significantly higher in cancer cells than in epithelial cells of control specimens. No correlations, however, were observed between oncogene product expression and tumor size, histologic type, or grade. As a group, tumors with axillary lymph node metastases expressed higher levels of ras p21 than nonmetastasizing tumors. However, because of the significant overlap in individual p21 values, it is unlikely that the immunohistochemical assay for p21 could be used to predict the behavior of mammary carcinomas.

Breast Neoplasms↗
PubMed1989

Ethanol fixation of bladder irrigation specimens for flow cytometric analysis. A multiinstitutional study from the bladder cancer flow cytometry network.

Ethanol preservation of voided and catheterized urine has long been the standard for urinary cytologic study. In this report ethanol preservation of bladder irrigation specimens was evaluated for flow cytometric analysis in a multiinstitutional study requiring specimen transport. Specimens from ten patients obtained at one center were preserved for varying periods of time in 50% ethanol, then distributed by express mail to four other participating centers, up to 3000 miles distant. On receipt, from 1 to 3 weeks after collection, the samples were processed and examined by flow cytometric study using propidium iodide as the fluorochrome. Forty-six of the 50 (92%) analyzed specimens gave satisfactory histograms. In 41 of the 46 adequate samples (89%), an aneuploid peak in the alcohol preserved (propidium iodide stained) specimen correlated well with the fresh (acridine orange stained) specimen. However, there was variable loss of DNA stainability with a broadening of the coefficient of variation in some alcohol-preserved specimens and an increase in cellular debris so that measurements of DNA index and percent hyperdiploid cells were considered unreliable. The authors conclude that ethanol preservation of bladder irrigation specimens for short periods of time may be a feasible alternative when flow cytometric analysis cannot be carried out on fresh specimens, but that this is not optimal fixation for specimens that must be transported and further studies of other fixatives are recommended.

Aneuploidy↗
PubMed1989

Check samples for laboratory self-assessment in DNA flow cytometry. The National Cancer Institute's Flow Cytometry Network experience.

The National Cancer Institute's Flow Cytometry Network (NCI-FCN) is attempting to facilitate the transfer of flow cytometry (FCM) of exfoliated bladder cells from the research laboratory to the clinical laboratory. Demonstrating interinstitutional consistency in FCM analysis of replicate specimens simulating clinical barbotage specimens, fixed to allow easy transportation and storage at room temperature was one specific objective. Simulated barbotage specimens were prepared by mixing cultured aneuploid bladder carcinoma cells with normal or mitogen-stimulated peripheral blood mononuclear cells in different ratios. The samples were fixed in 10% formalin for 30 minutes, stored in buffer, and enucleated with pepsin, pH 1.5, before staining with propidium iodide for FCM DNA analysis. Preservation in ethanol or other common DNA cytochemical reagents was found to be unsatisfactory. In contrast, the formalin-fixed samples showed excellent preservation of quantitative DNA fluorescence and coefficient of variation of histogram peaks for over 2 weeks. Exchange of eight fixed specimens among five network laboratories that analyzed them as "unknowns" showed good overall agreement on histogram data and interpretation, although some noteworthy interlaboratory differences were found. This technique could be used for self-assessment surveys of clinical laboratory performance in DNA FCM of bladder barbotage specimens.

Cell Count↗
PubMed1989

The Papanicolaou test for cervical cancer detection. A triumph and a tragedy.

The complex detection system leading to the discovery and treatment of precancerous lesions and early cancer of the uterine cervix is described in detail and discussed. By far the most difficult and underestimated component of this system is the screening and interpretation of cervical (Papanicolaou) smears. Cytologic case finding may fail because of inadequate samples, insufficient time devoted to screening, or human fatigue. Other weak points of the system, such as an inadequate clinical component, inadequate patient compliance, poor reproducibility of diagnoses, and ineffective aftercare, are also described. For example, obtaining a second smear to confirm or refute a diagnosis of cellular atypia is often a misleading practice. Although this cancer detection system has been shown to be effective in reducing the rate of morbidity and mortality from invasive cervical cancer in appropriately screened populations, there is no evidence that the Papanicolaou test has succeeded anywhere in complete eradication of this theoretically preventable disease. It is important to inform the public about the potential failures of the system and the reasons for them.

Carcinoma↗
PubMed1989

Measurement variability in DNA flow cytometry of replicate samples.

A Bladder Cancer Flow Cytometry Network study has been carried out aimed at identification of the sources of inter- and intralaboratory variability. Replicate "cocktail" samples containing a mixture of peripheral blood lymphocytes and an aneuploid cell line and samples of peripheral blood lymphocytes serving as a DNA reference standard were distributed to five network laboratories. The samples were stained for DNA using propidium iodide, with each laboratory using its own staining protocol. Sets of these samples were analyzed by flow cytometry to obtain cellular DNA distributions. DNA index and hyperdiploid fraction were calculated for each histogram using an automated technique. Results were evaluated by analysis of variance to identify sources of variability. Three important sources of variation were found that affect flow cytometry in general and- the transportability of flow cytometry results to routine clinical use in particular. The significant variation among laboratories that is constant across time most probably represents stable differences in instrumentation, instrument set-up, and laboratory techniques. This variation can be compensated for, if it is known and stable, to develop transportable classification criteria. The second type of variation, termed the interaction component, represents differences among laboratories that are not constant across time. Sources of this variation include inconsistency in sample preparation, staining, and analysis. The elimination of this type of variation is required for meaningful comparison of data within and among laboratories and the creation of interlaboratory data-bases. The third type of variation represents pure measurement variability and affects the sensitivity of the technique.

Cell Line↗
PubMed1989

Flow cytometric measurements of DNA and other cell components in human tumors: a critical appraisal.

Fundamental principles of flow cytometry with emphasis on DNA measurements and cell cycle analysis in human cells and tissues are summarized. Some of the pitfalls of cell preparation techniques and histogram interpretation are discussed at length. While consensus has been reached for some organs and tumors that DNA quantitation by flow cytometry (or image cytometry) may be of prognostic value, for most cancers studied to date the information remains incomplete. Thoroughly lacking are well-structured prospective studies because retrospective studies, while suggestive, may not necessarily be of the same value. Potential usefulness of other tumor markers is briefly discussed. Many fundamental questions concerning definitions of "diploid" and "aneuploid" tumors have not been satisfactorily settled. While the goal of "objective measurements" is worthy of further pursuit, the interpretation of results is often highly subjective. The biologic reasons for behavioral differences between diploid and aneuploid tumors are still totally obscure.

Cell Cycle↗
PubMed1989

Pseudosarcomatous stromal reaction in primary and metastatic urothelial carcinoma. A source of diagnostic difficulty.

We report five urothelial carcinomas (one primary and four metastatic) with pseudosarcomatous stromal reaction. The exuberant stromal reaction led to a histologic misdiagnosis in three of the original small biopsy specimens. The differential diagnoses of primary spindle cell lesions of urinary tract include spindle cell carcinoma, carcinosarcoma, sarcoma, and benign pseudosarcomatous lesions. The distinction between those conditions and urothelial carcinomas with pseudosarcomatous stromal reaction is obviously of great clinical significance. In an initial small biopsy specimen, it may be difficult to make such a distinction. Immunostaining for cytokeratin and examination of more material should be performed. In our study of metastatic urothelial carcinomas with pseudosarcomatous stromal reaction, clinicopathologic correlations along with immunostaining for keratin proved to be useful. The stromal inductive capability of transplanted urothelium, which has been established in animal experiments, has occasionally also been reported in humans. The malignant urothelium in humans similarly appears to be capable of inducing stromal reaction.

Aged↗
PubMed1989

Human polyomavirus: lack of relationship of viruria to prolonged or severe hemorrhagic cystitis after bone marrow transplant.

Urine cytology was studied prospectively for the presence of human polyomavirus (HPV) in 17 consecutive patients undergoing marrow transplantation and correlated with hematuria and hemorrhagic cystitis. Of the 15 evaluable patients, nine had cytologic findings consistent with HPV infection during the first month after transplantation. Of these nine patients, two had gross and seven had microscopic hematuria, all without symptoms of cystitis. Hematuria resolved within 30 days of onset, although three patients had persistent cytologic evidence of HPV until 100 days after transplantation. During the follow-up ranging from 8 to 14 months, none of the patients developed hemorrhagic cystitis. Our data do not support the relationship between HPV and prolonged or severe hemorrhagic cystitis previously suggested by others, nor did we see any late onset hemorrhagic cystitis.

Adult↗
PubMed1989

Cervical and vaginal squamous cell abnormalities in women infected with human immunodeficiency virus.

We sought to determine whether women infected with human immunodeficiency virus (HIV) had cervicovaginal cellular changes suggesting lower genital tract neoplasia or human papillomavirus (HPV) infection at a rate different from that in women without HIV infection. In a blinded fashion, cytological preparations of cervicovaginal smears from women infected with the HIV were analyzed and compared to preparations from women at high risk for but not infected with HIV. Eleven of 35 (31%) HIV-infected subjects had evidence of squamous abnormalities compared with 1 of 23 (4%) non-HIV-infected women (p = 0.019). Nine of 35 (26%) HIV-infected women had cytohistological evidence of human papillomavirus (HPV) infection compared to 1 of 23 (4%) non-HIV-infected women (p = 0.072). We conclude that HIV-infected women have a high prevalence of cervical and vaginal cytological abnormalities and evidence of genital HPV infection. Further study is necessary to determine whether there is an increased risk for cervicovaginal neoplastic disorders in women infected with HIV.

Adult↗
PubMed1989

A selective mapping algorithm for computer analysis of voided urine cell images.

One of the fundamental targets of the automated image analysis of cytologic preparations is the reduction of computer classification errors due to cells or other objects that do not lend themselves to image segmentation or that have morphologic features that may mislead the cell classification schemes. In prior work from this laboratory, the achievement of this goal was attempted by hierarchical analysis of sequential microscopic objects at high resolution. This paper reports on the successful development and implementation of an automated "selective mapping algorithm" that selects cells at low power for further analysis and eliminates a large proportion of unwanted "objects." The algorithm classifies the objects and extracts appropriate features from a 256 X 240 digital image obtained via a 10 X planachromatic objective. The five-node binary tree classifier used in this triage is described. The algorithm was trained and tested initially on 501 visually classified microscopic "objects," resulting in a correct acceptance rate of 61.3% and correct rejection rate of 81.3%. The selective mapping algorithm was subsequently integrated into the video-based image analysis system constructed at the Montefiore Medical Center for the diagnostic evaluation of sediments of voided urine. The algorithm was then tested on ten cytocentrifuge preparations for a preliminary evaluation of its performance. Up to 100 "objects" per case were selected by the algorithm for further classification by the computer at high power. Of the 810 "objects" selected by the selective mapping algorithm, 344 (42.5%) were classified by the computer at high resolution as cells of diagnostic value ("WELL" cells) and 466 were rejected.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1988

Interinstitutional variability in DNA flow cytometric analysis of tumors. The National Cancer Institute's Flow Cytometry Network Experience.

Flow cytometric DNA analysis of human urinary bladder specimens may be clinically useful for prognosis in transitional cell (urothelial) carcinoma and for detecting recurrence after treatment. However, many important methodological differences exist among institutions which have described this technique, and it has not previously been shown that data from different institutions are comparable. The National Cancer Institute has created a Flow Cytometry Network to address the need for technology assessment of flow cytometry. This report describes the independent flow cytometric analysis and interpretation of "unknown" paraffin-embedded bladder tumor specimens by the five Network institutions. Although important differences in method existed among the institutions, substantial agreement was achieved in actual data generated and their interpretation. This suggests that a consensus regarding acceptable laboratory performance of this technique could be reached, which should facilitate its more widespread clinical implementation.

Carcinoma, Transitional Cell↗
PubMed1988

Comparison of automated and manual techniques for analysis of DNA frequency distributions in bladder washings.

Quantitative methods for interpretation of flow cytometry DNA histograms are required for the widespread clinical use of this technology. The usefulness of a histogram analysis technique in this setting requires that it be operator independent, easy to implement in a clinical laboratory, and provide high sensitivity to the desired information. Additionally, the technique must be tolerant of the relatively low signal-to-noise ratios often found in DNA distributions obtained from clinical samples. Among the factors that have been used to assess the malignant potential of tumors are the presence of an aneuploid population, the proportion of hyperdiploid cells, the width of the G1 peak, the DNA index, and the fraction of cells in S. A computer-based method has been developed for extraction of the above-mentioned features from DNA histograms. The program detects peaks in the histogram and uses straight-line fits to the cumulative frequency distribution to define cell population bounds. A test set of 44 histograms compiled from bladder irrigation specimens obtained from patients with a present or past history of transitional cell carcinoma (TCC) was analyzed by five collaborating laboratories forming a Network sponsored by the National Cancer Institute (NCI). This test set was used to evaluate the performance of the computer-based method by comparing results with those of four expert observers. In this preliminary analysis, perfect agreement was found in the detection of aneuploid cell populations by all observers and the computer-based method. Correlation of percent hyperdiploid cell fraction was also excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1988

Cell cycle-dependent reactivity with the monoclonal antibody Ki-67 during myeloid cell differentiation.

The specificity and sensitivity of the monoclonal antibody Ki-67 in identifying proliferating cell compartments was tested with the human promyelocytic leukemia cell line HL-60 using multi-parameter flow cytometry. While correlated measurements of DNA content and Ki-67 immunofluorescence indicated that the antigen was present in all phases of the cell cycle, reactivity with the antibody was highest in proliferating S and G2+M cells. The analysis of the BrdU content of cells sorted on the basis of reactivity with Ki-67 showed a correlation between Ki-67 reactivity and BrdU uptake. In HL-60 cells induced to differentiate with dimethyl sulfoxide (DMSO), the loss of reactivity with Ki-67 paralleled the exit of cells from the cell cycle. This was not observed in DMSO-resistant HL-60 cells. These results validate the usefulness of the Ki-67 antibody for determining the proliferative stage of mammalian cells in culture.

Antibodies, Monoclonal↗