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PubMed2003

Prognostic impact of DNA ploidy pattern, S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) in patients with primary gastric lymphoma.

BACKGROUND: DNA ploidy, S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) are considered to be significant prognostic factors in non-Hodgkin lymphomas. However, reports on their prognostic importance in gastric lymphoma patients are relatively lacking. METHODS: In the present study, we retrospectively studied the above-mentioned parameters in 29 patients with primary gastric lymphoma; 11/29 had B-low grade mucosa associated lymphoid tissue lymphoma (B-MALT), while 18/29 had diffuse large B-cell lymphoma (DLBCL), according to WHO classification. Proliferative activity was studied by staining against PCNA; in addition, the prognostic significance of DNA ploidy and SPF, as determined by flow cytometry, were investigated and compared to the results of the PCNA stainings. RESULTS: Seven out of 29 patients were found to have aneuploid tumors; DNA index values were >1 for all aneuploid lymphomas. There was no difference in DNA aneuploidy in MALT vs. DLBCL. The mean percentage of SPF was 11.4. SPF was found significantly lower in MALT vs. DLBCL (P < 0.05). The mean percentage of PCNA positive tumor cells was 52.6. PCNA protein expression was significantly lower in MALT vs. DLBCL (P < 0.0001). There was a significant positive correlation between PCNA score and SPF (P < 0.01, by Spearman analysis). DNA ploidy had no impact on survival in the present study. Both SPF and PCNA expression were important prognostic factors in the univariate analysis; however, in the multivariate analysis, the only independent prognostic factor for survival was PCNA expression. CONCLUSIONS: These findings indicate that SPF and PCNA are significant prognostic factors in patients with primary gastric lymphomas. However, in the present study, DNA ploidy had no impact on survival in patients with primary gastric lymphomas.

Adult↗

PubMed1990

Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms.

Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated with the cell cycle. A monoclonal antibody, PC10, that recognizes a fixation and processing resistant epitope has been used to investigate its tissue distribution. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. PCNA immunoreactivity is induced in lectin stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine incorporation and the number of cells with PCNA immunoreactivity is reduced by induction of differentiation in HL60 cells. In non-Hodgkin's lymphomas a linear relation between Ki67 and PCNA staining was demonstrated. These data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation. However, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost. In some breast and pancreatic tumours there is apparent deregulation of PCNA with increased expression in tissues adjacent to the tumours. The over-expression in some tumours and in adjacent morphologically normal tissue may represent autocrine or paracrine growth factor influence on PCNA gene expression.

Adult↗

PubMed1992

Relationship of proliferating cell nuclear antigen (PCNA) in prostatic carcinomas to various clinical parameters.

Proliferating cell nuclear antigen (PCNA) expression was determined immunohistochemically, using a monoclonal antibody PC10, in 102 prostatic carcinoma samples and in prostate tissue from 21 patients with benign prostatic hyperplasis (BPH). The percentage of cells with stained nuclei ranged from 1% to 58% in the carcinoma specimens and 0% to 10% in the BPH specimens. A semiquantitative scoring system was devised for the degree of PCNA positivity observed in the tumors. Statistical analysis of the PCNA score in relation to the histological grade of the tumors gave a significant positive or negative correlation between these parameters P less than 0.001. No significant correlation between PCNA score was, however, seen with metastatic status, T category (TMN classification) of the primary tumor, or the patient's age at diagnosis. In 65 prostatic cancer patients of known survival, those individuals whose tumors had a PCNA score of +/- (less than 10% of nuclei stained) were compared with those patients whose tumors were either 1+, 2+, or 3+ (greater than 10% of nuclei stained). Life table analysis of the two groups indicated that the patients with the lower PCNA score survived significantly longer than those with the higher PCNA scores, P less than 0.04. Comparison of the Ki-67 expression in frozen sections with the PCNA expression in wax-embedded tissue of 86 prostatic carcinomas was also undertaken. A significant correlation between these two parameters was found, P less than 0.001, although the growth fraction estimated by Ki-67 expression was generally lower than that given by the PCNA scoring system.

Antibodies, Monoclonal↗

PubMed2000

The PCNA from Thermococcus fumicolans functionally interacts with DNA polymerase delta.

We have cloned the gene encoding proliferating cell nuclear antigen (PCNA) from the hyperthermophilic euryarchaeote Thermococcus fumicolans (Tfu). Tfu PCNA contains 250 amino acids with a calculated M(r) of 28,000 and is 26% identical to human PCNA. Next, Tfu PCNA was overexpressed in Escherichia coli and it showed an apparent molecular mass of 33.5 kDa. The purified Tfu PCNA was tested first with recombinant Tfu DNA polymerase I (Tfu pol) and second with calf thymus DNA polymerase delta (pol delta). When tested with the homologous Tfu pol on bacteriophage lambda DNA, large amounts of Tfu PCNA were required to obtain two- to threefold stimulation. Surprisingly, however, Tfu PCNA was much more efficient than human PCNA in stimulating calf thymus pol delta. Our data suggest that PCNA has been functionally conserved not only within eukaryotes but also from hyperthermophilic euryarchaeotes to mammals.

Amino Acid Sequence↗

PubMed2001

Use of peptides from p21 (Waf1/Cip1) to investigate PCNA function in Xenopus egg extracts.

Cell-free systems derived from unfertilized Xenopus eggs have been particularly informative in the study of the regulation and biochemistry of DNA replication. We have developed a Xenopus-based system to analyze proliferating cell nuclear antigen (PCNA)-specific effects on the functional properties of egg extracts. To do this, we have coupled peptides derived from p21 (Waf1/Cip1) to beads and used these to deplete PCNA from Xenopus egg extracts. The effect on various aspects of DNA replication can be analyzed after the readdition of PCNA and other purified proteins. Using this system, we have shown that replication of single-stranded M13 DNA is entirely dependent upon PCNA. By adding exogenous T7 DNA polymerase to PCNA-depleted extracts, we have uncoupled processive DNA replication from PCNA activity and so created an experimental system to analyze the dependence of postreplicative processes on PCNA function. We have shown that successful chromatin assembly is specifically dependent on PCNA. However, systems for analyzing the far more complex mechanisms required for the replication of nuclear double-stranded DNA have proved so far to be refractory to specific PCNA depletion.

Animals↗

PubMed1999

Drosophila replication and repair proteins: proliferating cell nuclear antigen (PCNA).

Proliferating cell nuclear antigen (PCNA), a protein intimately involved in both replication and repair, has been identified in eukaryotes at all levels of evolution. Is primary sequence, Drosophila melanogaster PCNA is 73% identical to mammalian PCNA. Moreover, it is able to substitute for mammalian PCNA in at least one intricate cell-free replication assay. Mutations in the gene for Drosophila PCNA, including some that are temperature sensitive, have been reported. Procedures are described for the biochemical purification of wild-type PCNA from a population of 6- to 18-h-old Drosophila embryos. Procedures were also developed for purification of unmodified wild-type Drosophila PCNA after induction of expression in Escherichia coli. An NH(2)-terminally His-tagged but otherwise wild-type Drosophila PCNA, as well as mutant His-tagged PCNA, were also engineered and purified to apparent homogeneity. Finally, an in situ polyacrylamide gel technique allows DNA polymerase assays to be performed on portions of single adults as well as single Drosophila embryos. This assay should tremendously facilitate systematic genetic studies of metazoan replication and repair.

Animals↗

PubMed1994

Effects of selected chemotherapeutic agents on PCNA expression in prostate carcinoma cell lines.

Bivariate flow cytometric analysis of proliferating cell nuclear antigen (PCNA) was performed on prostate carcinoma cell lines (PC-3, DU-145). For both cell lines 100% methanol fixation provided optimal fluorescence intensity of PCNA. The ratio of PCNA/DNA increased in late G1 through early S/phase, followed by a decrease in mid- and late S and enhancement in G2/M phase. PCNA expression was increased in G2/M phase cells treated for 48 h with vinblastine. A slight decrease in PCNA expression was observed with cyclohexamide treatment. Hydroxyurea induced an increase in S-phase fraction along with enhanced PCNA expression. Methotrexate and Adriamycin had little effect on the cell cycle compartments of PC-3 or DU-145; however, methotrexate decreased PCNA expression, while Adriamycin enhanced it. Cisplatin increased S-phase in both cell lines, increasing PCNA expression in PC-3 and decreasing it in DU-145 cells. The data on the effects of drug treatment point to a dissociation between PCNA expression and S-phase fraction as calculated from the DNA distribution. In some cases, e.g., the cisplatin studies, different effects were obtained in the two different cell lines treated with the same drugs. Whether changes in PCNA expression will provide more useful information than S-phase fraction for evaluation of potential antitumor drugs is not known.

Antineoplastic Agents↗

PubMed1991

Induction of proliferating cell nuclear antigen (PCNA)-immunoreactive cells in goldfish retina following intravitreal injection with 6-hydroxydopamine.

1. The dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA), was injected intravitreally into the eyes of juvenile (5- to 6-cm) goldfish. 2. Proliferation of rod neuroblasts caused by 6-OHDA (2 micrograms in 2 microliters saline) was detected in retinal wholemounts by immunofluorescence for proliferating cell nuclear antigen (PCNA) 3, 7, 14, 20, or 30 days after injection. 3. The injected dose of 6-OHDA was sufficient to cause permanent loss of dopaminergic interplexiform and serotonergic amacrine cells in the injected eye but not in the contralateral control eye. 4. 6-OHDA increased the density (mm-2) of PCNA-ir cells in the outer nuclear layer (ONL) of the injected eye to 2.65 times the initial density 20-30 days after injection, and it increased the density of PCNA-ir cells in the ONL of the contralateral, untreated eye, equally but after a delay of less than or equal to 7 days with respect to the injected eye. 5. 6-OHDA also increased the density of PCNA-ir cells in the inner nuclear layer (INL) to greater than 20 times the initial density 7 days after injection, followed by a rapid decline almost to control levels by 14 days after injection. 6. The sequence of responses to 6-OHDA, with PCNA-ir cells first scattered in the ONL and then clustered in the INL, suggests that neuroblasts from the ONL migrate to the INL to compensate for toxin-induced cell loss. 7. Double staining for 5-bromodeoxyuridine (BrUdR; a thymidine analogue) and PCNA, carried out on 7 days after intravitreal injection with 6-OHDA, showed that 77% of all PCNA-ir cells in the outer nuclear layer had been in S phase during the previous 24 hr. 8. Immunoreactivity for PCNA was found to be a valid marker for rod neuroblasts which have entered S phase within 1-2 days before sampling and was shown to be especially convenient for investigating the distribution of proliferating cells in whole mounts. 9. In controls injected unilaterally with saline or saline plus 1% dimethyl sulfoxide (DMSO), the differences in densities of PCNA-ir rod precursor nuclei 2-30 days after injection vs. day 0 (uninjected) were statistically insignificant in both injected and uninjected eyes (Negishi et al., 1991). Therefore the local effect of injecting 6-OHDA was due to 6-OHDA itself, not to mechanical damage or nonspecific actions of foreign substances.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

Hepatocyte regeneration in chronic hepatitis C and interferon treatment: analysis of immunohistological identification of proliferating cell nuclear antigen (PCNA).

To evaluate the usefulness of proliferating cell nuclear antigen (PCNA) immunostaining in the assessment of the efficacy of interferon (IFN) therapy in chronic hepatitis C, we investigated the proliferative activity of hepatocytes in 67 patients with chronic hepatitis C, using this immunostaining method. The percentage of PCNA-positive hepatocytes was 2.4% in patients with chronic persistent hepatitis, 2.5% in those with chronic aggressive hepatitis 2A, and 3.9% in those with chronic aggressive hepatitis 2B. The PCNA count increased with the progression of the liver disease. Patients were classified as complete, partial, and non-responders to IFN; the percentage of PCNA-positive hepatocytes before IFN therapy was 1.6% in the complete responders, 3.9% in the partial responders, and 4.9% in the non-responders. There was a significant negative correlation between the percentage of PCNA-positive hepatocytes and the response to IFN treatment. Thirty-two of 53 cases (60.4%) in which the PCNA labeling index (LI) was less than 5.0 were complete responders compared with 13 of 14 cases (92.9%) in which the PCNA LI was higher than 5.0, representing partial responders or non-responders (P < 0.001). Most complete responders had a low PCNA LI, irrespective of HCV genotype. Our findings indicate that PCNA immunostaining is a simple and reliable index of cell proliferation in liver regeneration, and may be a useful predictor of the response to IFN treatment in chronic hepatitis C.

Adult↗

PubMed1994

Evaluation of hepatic proliferative activity in chronic liver diseases and hepatocellular carcinomas by proliferating cell nuclear antigen (PCNA) immunohistochemical staining of methanol-fixed tissues.

The proliferative activity of chronic liver diseases and hepatocellular carcinomas (HCCs) was studied by PCNA immunohistochemistry. Human liver tissues were obtained by surgical operation or needle biopsy, and PCNA was detected by immunohistochemistry. PCNA-labelling indices (PCNA-LIs) of methanol-fixed tissues corresponded with the incidence of S-phase cells previously reported, whereas paraformaldehyde-fixed tissues showed extremely high PCNA-LIs in all specimens. Therefore, methanol-fixed tissues were used for evaluation. The PCNA-LIs of the methanol-fixed tissues were: normal liver 0.78 +/- 0.38%, chronic persistent hepatitis 1.06 +/- 0.86%, chronic aggressive hepatitis 2A 1.01 +/- 0.50%, chronic aggressive hepatitis 2B 4.20 +/- 1.79%, inactive cirrhosis 0.81 +/- 0.49%, active cirrhosis 1.96 +/- 0.93%, HCC of Edmondson's type I 4.83 +/- 1.98%, type II 6.65 +/- 1.69%, and type III 38.7 +/- 30.6%. PCNA-positive cells showed little specific distribution; in periportal areas in chronic hepatitis, at the margins of pseudolobules in cirrhosis, and throughout the tumor in HCC. These findings indicated that proliferative activity increased during the progression of chronic hepatitis, but that it decreased at the stage of cirrhosis. In chronic liver diseases, the PCNA-LIs reflected hepatitis activity. HCC showed higher proliferative activity than liver cirrhosis, and the histological grade was correlated with the PCNA-LI.

Analysis of Variance↗

PubMed1996

Cloning, sequencing, and chromosomal localization of two tandemly arranged human pseudogenes for the proliferating cell nuclear antigen (PCNA).

We have characterized a human genomic clone carrying two pseudogenes for the proliferating cell nuclear antigen (PCNA), which were tandemly arranged on human Chromosome (Chr) 4. One is a processed pseudogene that showed a 73% nucleotide homology to the human PCNA cDNA and possessed none of the introns existing in the functional PCNA gene. This pseudogene presumably arose by reverse transcription of a PCNA mRNA followed by integration of the cDNA into the genome. The other is a 5' and 3' truncated pseudogene that showed a nucleotide homology to a 3' region of the exon 4 and to a 5' region of the exon 5 of the PCNA gene and did not have the intronic sequence between the exons 4 and 5. Both pseudogenes had the same nucleotide deletion as compared with the human functional PCNA gene. A phylogenetic analysis of PCNA gene family, including the functional PCNA gene and another PCNA pseudogene located on a different chromosome, revealed that the truncated pseudogene exhibits the closest evolutionary relationship with the processed pseudogene, suggesting that the truncated pseudogene was generated by duplication of the processed pseudogene after translocation to Chr 4. Furthermore, fluorescence in situ hybridization revealed that these pseudogenes are located on the long arm of Chr 4, 4q24.

Animals↗

PubMed2005

Proliferating cell nuclear antigen (PCNA) as a proliferative marker during embryonic and adult zebrafish hematopoiesis.

We investigated the expression of proliferative cell nuclear antigen (PCNA) in zebrafish to delineate the proliferative hematopoietic component during adult and embryonic hematopoiesis. Immunostaining for PCNA and enhanced green fluorescence protein (eGFP) was performed in wild-type and fli1-eGFP (endothelial marker) and gata1-eGFP (erythroid cell marker) transgenic fish. Expression of PCNA mRNA was examined in wild-type and chordin morphant embryos. In adult zebrafish kidney, the renal tubules are surrounded by endothelial cells and it is separated into hematopoietic and excretory compartments. PCNA was expressed in hematopoietic progenitor cells but not in mature neutrophils, eosinophils or erythroid cells. Some PCNA+ cells are scattered in the hematopoietic compartment of the kidney while others are closely associated with renal tubular cells. PCNA was also expressed in spermatogonial stem cells and intestine crypts, consistent with its role in cell proliferation and DNA synthesis. In embryos, PCNA is expressed in the brain, spinal cord and intermediate cell mass (ICM) at 24 h-post fertilization. In chordin morphants, PCNA is significantly upregulated in the expanded ICM. Therefore, PCNA can be used to mark cell proliferation in zebrafish hematopoietic tissues and to identify a population of progenitor cells whose significance would have to be further investigated.

Animals↗

PubMed2005

Nucleophosmin/B23 regulates PCNA promoter through YY1.

Ectopic over-expression of nucleophosmin/B23 caused a marked up-regulation in the amounts of Yin Yang 1 (YY1) and proliferating cellular nuclear antigen (PCNA) proteins. Transfection with nucleophosmin/B23-targeting siRNA induced a decrease in the intracellular amounts of nucleophosmin/B23, YY1, and PCNA. PCNA expression and its promoter activity were attenuated either by nucleophosmin/B23-siRNA or YY1-siRNA. The ChIP assay showed that positive regulation of PCNA is achieved by binding of YY1 to the initiation site of PCNA promoter. The binding of YY1 to the PCNA promoter and histone H4 acetylation was significantly decreased in nucleophosmin/B23-siRNA-treated cells as compared to control vector-transfected cells. Mutation in YY1 binding site resulted in the loss of PCNA promoter activity and the binding of YY1 to the promoter. The results have indicated that YY1 binds to the initiation site of the PCNA promoter along with histone H4 acetylation, leading to transcriptional activity. We have demonstrated that nucleophosmin/B23 plays an important role in the regulation of PCNA through YY1.

Animals↗

PubMed2005

Higher expressions of p53 and proliferating cell nuclear antigen (PCNA) in atrophic oral lichen planus and patients with areca quid chewing.

OBJECTIVE: The aim of the study was to examine the expressions of p53 and proliferating cell nuclear antigen (PCNA) in oral lichen planus (OLP) in relation to its clinical behavior and the patients' oral habits. STUDY DESIGN: Immunohistochemical study was carried out to investigate the expressions of p53 and PCNA in 56 OLP specimens. The results were correlated with the clinical behavior of the disease and the patients' oral habits. The expression rates were further compared with those of normal oral mucosa (NOM), epithelial hyperkeratosis (EH), epithelial dysplasia (ED), and squamous cell carcinoma (SCC). RESULTS: The staining rate of p53 (28.6%) and PCNA labeling index (LI) (27.6 +/- 8.8%) in OLP were similar to those in EH ( P = .868, .074, respectively), but higher than those of NOM and lower than those of ED and SCC (all P < .05). In OLP, no significant correlations were found between p53 or PCNA expression and the patients' age, gender, lesion duration, location, size, number of site, presence of pain, presence of local irritant, and the habits of alcohol drinking and cigarette smoking (all P > .05). In addition, the mean PCNA LI of p53+ cases was close to that of p53- cases (P = .38). However, the staining rate of p53 in OLP was higher in areca quid (AQ) chewers compared to abstainers (P = .001), and the mean PCNA LI in atrophic cases was higher than that in hypertrophic cases (P = .029). Interestingly, the staining rate of p53 and mean PCNA LI were significantly increased in AQ chewers with atrophic OLP (100%, 36.7% +/- 9.0%, respectively), which were similar to those in ED and SCC (all P > .05). CONCLUSIONS: Although this study could not confirm the precancerous nature of OLP by the relatively low p53 and PCNA expression, the results do suggest that atrophic form OLP and patients with AQ chewing habit may have a higher disease activity in view of higher expression rates of p53 and PCNA in the lesions.

Adolescent↗

PubMed2000

Expression of proliferating cell nuclear antigen (PCNA) in the adult and developing mouse nervous system.

Proliferating cell nuclear antigen (PCNA) is essential for the function of DNA polymerases delta and epsilon. Because proliferating cell nuclear antigen is required for DNA replication and repair, PCNA is abundantly expressed in proliferating cells. Interestingly, PCNA mRNA has also been detected in the adult mouse brain by Northern blot analysis. In this study, two monoclonal antibodies against PCNA, PC10 and 19F4, were used for Western blot analysis. Monoclonal antibody PC10, but not 19F4, detected a band in the adult mouse brain extract. This PC10-reactive protein in the brain displayed a more acidic isoelectric point than PCNA by two-dimensional gel electrophoresis. In situ hybridization showed that PCNA mRNA was abundantly expressed in the adult mouse subventricular zone. Additionally, relatively low levels of PCNA mRNA expression were also found in neurons throughout the central nervous system, however, no hybridization was observed in the white matter. Immunohistochemistry was also performed using 19F4 and PC10, and staining of progenitor cell nuclei in the subventricular zone was observed with both antibodies. Whereas 19F4 immunostaining was restricted to progenitor cells, PC10 immunostaining was also found in postmitotic nonproliferating cell nuclei. In the cortical neuroepithelium of developing mice, the distribution of PC10 immunoreactivity was wider than that of 19F4 immunoreactivity and PCNA mRNA expression. These results suggest that proliferating cell nuclear antigen mRNA is expressed not only in proliferating cells but also in nonproliferating cells such as neurons. The protein recognized only with PC10 may be a modified, most probably a phosphorylated PCNA.

Age Factors↗

PubMed1998

Proliferating cell nuclear antigen (PCNA) immunolabeling as a prognostic factor in invasive ductal carcinoma of the breast in Taiwan.

To evaluate the prognostic significance of proliferating cell nuclear antigen (PCNA) in breast cancer, an immunohistochemical assay was performed in 150 patients with invasive ductal carcinomas. The PCNA labeling index (PCNA-LI) was classified into two subgroups at a cut-off point of 45% that gave the best prognostic estimates for PCNA in survival analyses. Seventy-eight tumors had a low PCNA-LI of < or =45% and 72 tumors had a high PCNA-LI of >45%. A high PCNA-LI correlated significantly with p53 overexpression (P<0.03), positive axillary node (P<0.04), short disease-free survival (P<0.001) and overall survival (P<0.0002), but not with other factors. In multivariate analysis, the PCNA-LI predicted the disease-free (P<0.008) and overall survival (P = 0.0007) independently. Our study indicates that the PCNA-LI has independent prognostic value.

Adult↗

PubMed1997

High PCNA index in meningiomas resistant to radiation therapy.

PURPOSE: Meningiomas are common intracranial tumors, often well controlled with surgical resection alone. While the efficacy of radiation therapy in improving local control and progression-free survival is well documented, prognostic data substantiate factors that are predictive of poor local control following definitive radiation therapy. PCNA is a DNA polymerase expressed at the highest levels in the S-phase, the most resistant portion of the cell cycle to ionizing radiation in vitro. We investigated the possible correlation between the levels of PCNA expression and the clinical outcome of patients treated with definitive radiation therapy. METHODS AND MATERIALS: Archival tissue was collected from 33 cases of meningioma treated at our institution for definitive radiation therapy between 1970 and 1990. Age-matched normal meningeal tissue and asymptomatic meningiomas removed at autopsy served as tissue controls. A standard ABC immumoperoxidase technique employing antibodies to PCNA, PC-10 (Dako, California) was used to stain specimen slides for PCNA. PCNA index was defined as the number of positive nuclei per 10 high-power fields at 400x magnification. Two independent observers scored the slides without prior knowledge of the cases at hand. RESULTS: Patients with high PCNA index were less likely to be controlled by therapeutic radiation (p < 0.001, Kaplan-Meier). All patients with a PCNA index greater that 25 failed radiation therapy. Using multivariate analyses, malignant (but not atypical), histology and PCNA index were significant predictors of progression following radiation therapy (p < 0.05, log rank). CONCLUSION: PCNA index may be a useful adjunct to more standard histopathologic criteria in the determination of meningioma local control and progression-free survival following therapeutic irradiation. Data on a more expanded population evaluated on a prospective basis will be needed before such criteria are routinely employed in the clinical setting.

Adult↗

PubMed2000

Expression of proliferating cell nuclear antigen (PCNA) in oral submucous fibrosis, oral epithelial hyperkeratosis and oral epithelial dysplasia in Taiwan.

To test whether the oral epithelia of oral submucous fibrosis (OSF), epithelial hyperkeratosis (EH) and epithelial dysplasia (ED) may have increased proliferative activity under the long-term exposure to areca quid ingredients and whether there is an increased expression of proliferating cell nuclear antigen (PCNA) in oral premalignant lesions with disease progression, we used an immunohistochemical technique with the mouse monoclonal antibody PC10 to investigate PCNA expression in histologic sections of OSF, EH, ED and normal oral mucosa (NOM). Positive PCNA staining was found mainly in basal and parabasal epithelial cells in all specimens of OSF, EH, ED and NOM. The mean PCNA labeling indices (LI) in NOM, OSF, EH and ED were 8.8+/-2.7%, 22.1+/-12.5%, 25.5+/-5. 2% and 44.9+/-15.4%, respectively. Significant differences in the PCNA LI were noted between NOM and OSF (P<0.01), EH (P<0.001) or ED (P<0.001), as well as between ED and OSF (P<0.001) or EH (P<0.01). The gradual increase of PCNA expression with the morphologic transformation of normal epithelial cells into dysplastic epithelial cells suggests that there is increased proliferative activity in oral premalignant lesions with disease progression. However, no significant correlation was found between PCNA LI in OSF epithelium and the clinicohistologic parameters of OSF. In addition, the mean PCNA LI of p53-positive OSF cases (23.7+/-12.0%) was very close to that of p53-negative OSF cases (23.9+/-13.1%), suggesting that there was no association between PCNA and p53 expression in OSF.

Adult↗