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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunohistochemical detection of PCNA/Cyclin, a nuclear protein associated with cell proliferation, represents a potentially useful tool for the study of tumor proliferative activity. Previous studies investigating the reactivity of anti-PCNA/Cyclin monoclonal antibody 19A2 have not clearly defined the population of proliferating cells with which 19A2 reacts in tissue sections. The authors describe a method for detection of PCNA/Cyclin in formalin-fixed, paraffin-embedded tissue using a routine biotin-streptavidin immunohistochemical system that employs an anti-IgM, mu-chain-specific second-stage antibody. The authors used this method to study the proliferative activity of 24 malignant lymphomas, consisting of 12 low-grade lymphomas (LGLs) and 12 intermediate-grade lymphomas (IGLs), and five reactive tonsils. 19A2 data was compared with Ki-67 labeling in frozen sections in the same group of cases. 19A2 provided easily detectable nuclear staining of proliferating cells with reactive cells demonstrating varying intensity of staining, this latter finding most likely due to the varying nuclear concentration of PCNA/Cyclin protein during the cell cycle. In tonsils, 19A2 reacted with germinal center cells and basal keratinocytes. In the malignant lymphomas, there was good correlation between 19A2 and Ki-67 data (r = 0.90, P less than 0.001). The subgroup of LGLs showed a mean PCNA/Cyclin of 26% and a mean Ki-67 of 28%. In the subgroup of IGLs, mean PCNA/Cyclin = 54% and mean Ki-67 = 59%. These results indicate that 19A2 detects a fraction of proliferating cells that is similar to that detected by Ki-67, ie, the growth fraction, and that 19A2 is a reliable marker of proliferative activity in uniformly handled, formalin-fixed, paraffin-embedded tissue.
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PMID:Growth fraction estimation of malignant lymphomas in formalin-fixed paraffin-embedded tissue using anti-PCNA/Cyclin 19A2. Correlation with Ki-67 labeling. 167 40

The relationship between interphase cytogenetics and tumor grade, stage, and proliferative activity was investigated in 27 transitional cell carcinomas of the urinary bladder. Using fluorescence in situ hybridization with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 7, 9, and 11 was detected within interphase nuclei in touch preparations from tumor biopsies. Monosomy of chromosome 9 was detected in 9 of 22 cases (41%), while tetrasomy for chromosomes 7 and 11 was detected in 10 of 26 (38%) and 6 of 23 (26%) cases, respectively. Copy number of chromosome 7 was the most highly correlated with increasing tumor grade (r2 = 0.616, P less than 0.001, Spearman rank correlation) or increasing pathological stage (r2 = 0.356, P less than 0.002). Copy number for chromosome 9 did not correlate with either grade or stage (P greater than 0.05). Tumor labeling index (LI) was determined after in vitro 5-bromodeoxyuridine incorporation, while proliferating cell nuclear antigen LI was determined immunohistochemically. Increasing LI by either method correlated with increasing copy number for all three chromosomes tested (r2 = 0.473, P less than 0.002 for 7; r2 = 0.384, P less than 0.01 for 11; and r2 = 0.316, P less than 0.05 for 9). Since high tumor grade, stage, and LI are all indicative of more aggressive tumor behavior and worse prognosis, these findings suggest that polysomy, especially for chromosome 7, may be highly predictive for bladder tumor aggressiveness.
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PMID:Centromeric copy number of chromosome 7 is strongly correlated with tumor grade and labeling index in human bladder cancer. 167 11

During a study using a monoclonal antibody directed against proliferating cell nuclear antigen (PCNA) to assess the proliferative activity of tumors, it was noted that the cytoplasm of Reed-Sternberg (RS) cells and variants of these cells in cases of Hodgkin's disease reacted very positively. This aberrant expression of PCNA has not been observed in any other tumor or in cells from normal tissues. The biological significance of this observation is currently unknown, but it may have diagnostic utility in detecting and identifying RS cells.
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PMID:Aberrant cytoplasmic expression of proliferating cell nuclear antigen in Hodgkin's disease. 167 80

Monoclonal antibodies to proliferating cell nuclear antigen (PCNA) were used to detect proliferating cells in pediatric tumors fixed in Carnoy's solution. The percentage of staining cells was quantified using image analysis and compared to the S + G2M phase fraction as determined by flow cytometry. Although there was a general correlation between these indices of cellular proliferation, some variation was noted between tumor systems as well as within a specific tumor type. In some cases this variation was easily explicable by the morphologic findings (e.g., tumor heterogeneity and sampling differences, stromal cell proliferation, necrosis, extramedullary hematopoiesis), whereas in others it appeared to be an intrinsic property of the cell line. It is concluded that PCNA immunostaining is a useful and reproducible method of assessing one aspect of cellular proliferative activity and especially of addressing the questions, "which cells are dividing and where?" It has some advantages over flow cytometry in that it maintains tissue integrity and morphologic relationships.
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PMID:Proliferating cell nuclear antigen (PCNA) and pediatric tumors: assessment of proliferative activity. 168 1

The proliferative capacity of brain-tumor cells was analyzed in vitro and in situ using monoclonal antibody (MAb) against deoxyribonucleic acid (DNA) polymerase alpha. For the in vitro studies, two cultured human glioma cell lines were investigated using MAb against DNA polymerase alpha, the MAb Ki-67, a serum against proliferating cell nuclear antigen (PCNA/cyclin), bromodeoxyuridine (BUdR), and an anti-BUdR MAb. During exponential growth of the cells, the percentage of polymerase alpha-positive cells (the "polymerase alpha score") ranged from 72.0% to 77.1%, the Ki-67-positive cells (the "Ki-67 score") ranged from 43.4% to 59.4%, the PCNA/cyclin-positive cells from 30.9% to 41.4%, and the BUdR labeling index from 28.6% to 39.3%. For the in situ studies, tissue from 60 human brain tumors and from two normal human brains was investigated and the polymerase alpha scores and Ki-67 scores were compared. In normal brain tissue, no immunostaining was found by either method. In brain tumors, both the polymerase alpha scores and the Ki-67 scores correlated with the histological grade of malignancy. Polymerase alpha scores were generally higher than Ki-67 scores in the same specimen, especially in malignant brain tumors. These findings suggest that immunostaining of DNA polymerase alpha is a convenient and important new method by which to estimate the cellular proliferation rate of brain tumors. Polymerase alpha scores may be closer to the growth fraction of the individual tumor than the MAb Ki-67 or other scores.
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PMID:Immunohistochemical demonstration of DNA polymerase alpha in human brain-tumor cells. 196 2

Although tumor DNA content and proliferation are usually determined by flow cytometry (FCM), quantitative microscopic image analysis is a viable alternative technique that also provides important histologic correlations. To compare these methods, we measured DNA content and proliferation in 54 consecutive breast cancers and 15 benign breast lesions by FCM and IA. DNA content determination was concordant in 49 of 54 cancers measured by FCM and IA. Four of the discordant cases were aneuploid by IA and diploid by FCM. There was good correlation between the DNA index (DI) measured by FCM and IA (r = 0.89, P less than 0.0001). Proliferation was assessed by IA quantitation of Ki-67 and PCNA/Cyclin antibody staining, as well as by flow cytometric S-phase fraction (SPF). Ki-67 positivity was greater in breast cancer than in benign controls (21.6% +/- 13.1% vs. 7.9% +/- 5.6% [P less than 0.0001]), as was PCNA/Cyclin positivity (10.2 +/- 6.7% vs. 2.7 +/- 2.5% [P less than 0.0001]). S-phase fraction measured by FCM was 7.9% +/- 5.7% for carcinomas and 3.17% +/- 2.1% for benign controls (P less than 0.003). Ki-67 and Cyclin staining, as well as SPF, were significantly increased in aneuploid compared to diploid tumors, and increased staining was associated with worsening nuclear grade. There were significant correlations between SPF and Ki-67 staining (r = 0.48, P less than 0.0001) and SPF and Cyclin staining (r = 0.48, P less than 0.0001). We conclude that FCM and IA provide comparable measurements of DNA content, although occasional discrepancies occur. Image analysis provides a valuable alternative method for assessing tumor cell proliferation and may offer certain advantages over FCM.
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PMID:Comparative assessment of proliferation and DNA content in breast carcinoma by image analysis and flow cytometry. 197

Our laboratory is studying genes involved in the regulation of the balance between cell growth and differentiation during embryonic development in Xenopus. We have analyzed the developmental expression of the proto-oncogenes c-myc, and KiRas 2B, the proliferating cell nuclear antigen (PCNA), and the tumor suppressor gene p53. These genes, usually expressed during cell proliferation, are expressed in the oocyte in large quantities, but the majority of their maternal RNAs are degraded by the gastrula stage. The expression of c-myc and the localization of the protein indicate that c-myc has the characteristics expected for a gene involved in the regulation of the mid-blastula transition, when zygotic expression is turned on in the embryo. Its expression during late development or during regeneration indicates that it enables the cells to remain competent for cycling during organogenesis. In vitro systems that reproduce the principal cellular functions during early development are used as model systems to understand the mechanisms involved in early embryogenesis.
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PMID:Genes and mechanisms involved in early embryonic development in Xenopus laevis. 197 4

Flow cytometry (FCM) is a useful method for clinical research of oncogene products since it can analyze proteins quantitatively which are located at cell surfaces or inside of cells. Oncogene products are now under study by FCM not only as tumor markers but also as functioning proteins in carcinogenesis. The examples of oncogene products analyzed by FCM are ras, myc, p53, myb and fos; those of cell-proliferation-related proteins are Ki-67, PCNA and DNA polymerase alpha. In some diseases the relationship between these proteins and disease classification, stage, pathophysiology, or prognosis have been clarified. Using dual color FCM of H-ras p21 and DNA, we analyzed the expression of H-ras p21 in human multiple myeloma and leukemias and found that H-ras p21 levels in multiple myeloma strongly correlated to the prognosis of patients (p = 0.03). When AML cells were stimulated by adding G-CSF, it was found that many cells proliferated but some were dying. The percentage of dying cells was small in one AML case whose myeloblasts showed increased expression of H-ras p21 by G-CSF stimulation. Together with other papers reviewed, it is conceivable that H-ras p21 expression is related to cell proliferation and inhibition of cell autolysis. Thus FCM is useful in the classification of the role of oncogene products in carcinogenesis in clinical cases.
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PMID:[Application of flow cytometry to the study of hematologic disorders: analysis of oncogene products]. 214 49

Replication of plasmid DNA molecules containing the simian virus 40 (SV40) origin of DNA replication has been reconstituted with seven highly purified cellular proteins plus the SV40 large tumor (T) antigen. Initiation of DNA synthesis is absolutely dependent upon T antigen, replication protein A, and the DNA polymerase alpha-primase complex and is stimulated by the catalytic subunit of protein phosphatase 2A. Efficient elongation of nascent chains additionally requires proliferating cell nuclear antigen, replication factor C, DNA topoisomerase I, and DNA polymerase delta. Electron microscopic studies indicate that DNA replication begins at the viral origin and proceeds via intermediates containing two forks that move in opposite directions. These findings indicate that the reconstituted replication reaction has many of the characteristics expected of authentic viral DNA replication.
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PMID:Reconstitution of simian virus 40 DNA replication with purified proteins. 217 60

Cell kinetic information is an important adjunct to histologically-based tumor classifications. Presently, cell kinetic data can be obtained from slide-based material only with monoclonal antibodies such as Ki-67, which require the use of frozen sections and cannot be applied to archival, paraffin-embedded material. Monoclonal antibodies have recently been generated to PCNA/cyclin, a 36 kd, S-phase-associated nuclear protein. The authors investigated whether monoclonal antibody 19A2 could be used to identify proliferating cells within fixed, embedded tissue sections. Deparaffinized sections of 41 methacarn-fixed human tumors were immunostained with 19A2 using a streptavidin biotin immunoperoxidase system. A semiquantitative scoring system was used to evaluate the fraction of cells that were PCNA/cyclin-positive, and this score was compared with cell kinetic data obtained from parallel flow cytometric S-phase analysis that had been performed on fresh samples of the same tumors. While there was general agreement between the slide-based, antibody-derived and the flow cytometrically-derived cell kinetic information, some discrepancies were observed. Some of the latter represented cases in which the anti-PCNA/cyclin antibody preparations demonstrated significant heterogeneity in the numbers of proliferating cells in different regions of the tumor. In other cases, a significant fraction of the positive cells corresponded to nontumor stromal and/or inflammatory cells. In these cases, the slide-based method provided more information about the tumor cell population than did the flow cytometry data. It is concluded that semiquantitative immunocytochemical analysis with anti-PCNA/cyclin antibodies may represent a simple, reproducible, yet powerful technique for the routine analysis of cell kinetic data in alcohol-fixed, paraffin-embedded tissue by the surgical pathologist.
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PMID:Analysis of proliferative grade using anti-PCNA/cyclin monoclonal antibodies in fixed, embedded tissues. Comparison with flow cytometric analysis. 256 87


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