Proliferating Cell Nuclear Antigen Scores Research Articles

Correlation between PCNA and AgNOR scores in non-Hodgkin's lymphomas using sequential staining technique.

To investigate the relation between the numbers of interphase silver stained nucleolar organiser regions (AgNORs) and immunolabelling with the monoclonal antibody PC10, which demonstrates proliferating nuclei by reacting with proliferating cell nuclear antigen (PCNA). The established sequential technique for the demonstration of interphase AgNORs and of antigens in paraffin wax sections was applied to a small series of non-Hodgkin's lymphomas (NHL) of both low and high grade type, together with specimens of palatine tonsil. The numbers of PCNA positive cells were counted in all specimens; in the tonsils the cells were counted in both follicle centres and in the interfollicular areas. The numbers of AgNORs in both PCNA positive and PCNA negative nuclei were then counted. Lower numbers of PCNA positive cells were found in the low grade than the high grade NHL (18-28.4% and 34.2-51.3%, respectively). This was reflected in the two areas of the palatine tonsils, the counts being higher in the follicle centre nuclei than in those in the interfollicular compartments. In general, the numbers of AgNORs were higher in the PCNA positive nuclei than in those lacking the antigen; however, a consistent finding was that relatively high AgNOR scores were observed in PCNA negative nuclei, especially in the high grade lymphomas. In the tonsils, however, the AgNOR counts were much lower in the nuclei lacking PCNA than in those containing it. The results obtained in the lymphomas were rather unexpected as, in general, previous studies have shown a close direct or indirect relation between AgNOR scores and proliferating cell counts. An explanation for these findings may be that the argyrophil proteins associated with proliferating cells remain in the nucleus in detectable form longer than the PCNA antigen, at least in neoplastic tissue.

Measurement of proliferating cell nuclear antigen (PCNA) and its clinical application in oral cancers

The PCNA score was measured in oral squamous cell carcinoma (SCC), and its relationship to other cell proliferation markers, Ki-67 score, S-phase fraction (SPF), and AgNORs counts was investigated. The PCNA score ranged from 0.4% to 43.5% with an average value of 22.8%, the Ki-67 score ranged from 4.9% to 40% with an average of 24.1%, and the SPF ranged from 0.4% to 32.5% with an average of 12.4%, while AgNORs counts ranged from 2.53/nucleus to 7.03/nucleus with an average of 4.74/nucleus. These four parameters were closely interrelated. There was a significant difference in PCNA score between malignant and nonmalignant lesions, suggesting a difference in growth activity. The mean PCNA score decreased significantly from 20.0% to 8.0% after cancer chemotherapy. The response of cancer cells to anticancer agents may be estimated by consecutive measurement of PCNA, since the PCNA score dropped after treatment in cases showing a favorable prognosis.

Proliferating cell nuclear antigen (PCNA) in atypical and malignant meningiomas

Because it is not easy to determine the tumor status o f meningiomas by current diagnostic procedures, we investigated these tumors immunohistochemically using the monoclonal antibody PC 10. This antibody recognizes a fixation- and processing-resistant epitope o f the proliferating cell nuclear antigen (PCNA), which is a 36-KD nuclear antigen associated with the cell cycle. We studied paraffin-embedded and f ormalin-fixed tissue specimens o f a group o f 21 atypicallmalignant meningiomas together with 18 benign meningiomas. PCNA staining results were compared with -the mean number o f silver-stained nucleolar organizer region-associated proteins (AgNORs), tumor grading, and mitotic indices o f these tumors. The percentage o f PCNA-positive cells was found to range between 0.1 and 40%, irrespective o f the tumor grade. When all tumors were collectively considered, no positive correlation was found between PCNA scores and histologic grading and only a weak one between PCNA score and mitotic index. A higher correlation was seen between AgNOR counts and tumor grading. Our results suggest that PCNA labeling and histologic grading seem to be independent parameters. The correlations found between AgNOR counts and tumor grading should be substantiated in further series.

Epithelial proliferation in Barrett's esophagus by proliferating cell nuclear antigen immunolocalization

Proliferating cell nuclear antigen (PCNA) is an auxiliary protein to DNA polymerase δ and is an absolute requirement for cellular proliferation. Specialized-type Barrett's columnar-lined esophagus (CLE) is associated with adenocarcinomatous change. In the present study, the cellular proliferation of three histological types of CLE was assessed by semi-quantitative evaluation of PCNA immunolocalization in 93 biopsy specimens from 45 patients using the murine monoclonal PC10. Statistical comparison was performed by the Mann-Whitney U test. Luminal surface cell labeling was uncommon in all histological types other than specialized CLE where 25 of the 43 biopsy specimens had at least occasional luminal surface cell labeling. Mean crypt labeling score of 4.06 for specialized type exceeded that for junctional (mean, 3.12; P < 0.001) and fundic types (mean, 1.6; P < 0.001). Gland cell PCNA staining scores for specialized-type CLE (mean, 3.18) exceeded that of junctional (mean, 1.97; P < 0.001) and fundic (mean, 1.04; P < 0.001). Summated PCNA scores for specialized-type, mean of 8.29, exceeded junctional mean score of 5.45 (P < 0.001) and fundic mean score of 2.76 (P < 0.001). PCNA immunolocalization reveals a high proportion of cells in cycle in the specialized-type CLE and expansion of the proliferative compartment, which may explain the association of specialized-type CLE with malignancy.

The expression of proliferating cell nuclear antigen in paraffin sections of peripheral, node-negative non-small cell lung cancer.

Cell proliferation of 40 peripheral, node-negative non-small cell lung cancers (NSCLC) treated with surgery alone was investigated by immunohistochemical analysis with the monoclonal antibody (MoAb) PC10, which recognizes a proliferating cell nuclear antigen (PCNA) in formalin-fixed and paraffin-embedded material. Results were correlated with DNA ploidy and S-phase fraction (SPF) analyzed by DNA flow cytometric study. Mitotic count (MC) was analyzed by light microscopic study and histopathologic features. PCNA immunoreactivity was seen in all samples and confined to the nuclei of cancer, but not to the surrounding, tumor-negative cells; its frequency ranged from 0-70% (median, 15%), and tumors expressed either a low (0-25%, n = 25) or intermediate (26-75%, n = 15) proliferative activity. There was no relationship between PCNA immunoreactivity and tumor stage or among size, histologic type, and mitotic count (MC). Tumors with intratumoral blood vessel invasion (BVI) showed a significantly higher (P less than 0.005) PCNA immunoreactivity than BVI-negative tumors. PCNA scores were significantly higher (P less than 0.005) in DNA aneuploid (n = 22) than in DNA diploid (n = 18) tumors and correlated significantly with the SPF of DNA aneuploid tumors (r = 0.825, P less than 0.0001), but not with diploid tumors (r = 0.002, P = 0.9). Intermediate proliferating tumors had a significantly higher (P less than 0.01) MC than their counterparts. In univariate analysis, significant predictors of survival were tumor classification (T1 versus T2), tumor size (less than or equal to 2.6 cm versus more than 2.6 cm), BVI (BVI-negative versus BVI-positive), MC (less than or equal to 8 versus more than 8), and PCNA immunoreactivity (low versus intermediate). DNA ploidy and SPF did not influence survival significantly. Only PCNA immunoreactivity retained its independent level of significance (P = 0.02) by multivariate analysis. It was concluded that PCNA immunostaining is a simple and clinically useful method for estimating cell proliferation in formalin-fixed, paraffin-embedded tissue of resected peripheral, node-negative NSCLC.

Argyrophilic nucleolar organizer region counts and proliferating cell nuclear antigen scores are two reliable indicators of survival in pharyngeal carcinoma.

The proliferative activity of pharyngeal carcinoma has been investigated by means of monoclonal antibody PC10 against proliferating cell nuclear antigen (PCNA/cyclin) and argyrophilic nucleolar organizer region (AgNOR) analysis in formalin-fixed, paraffin-embedded biopsies from 45 primary squamous and undifferentiated carcinomas, prior to therapy. The correlation between AgNOR counts and PCNA(PC10) scores was highly significant (r = 0.73; P < 0.0001) as determined by Pearson's correlation coefficient. Moreover, the univariate Kaplan-Meier survival analysis showed a significant correlation between 3- and 5-year survival rates and the mean AgNOR number per tumour cell (P = 0.0003) or the percentage of PCNA(PC10)-positive cells (P = 0.0001). Our results indicate that both AgNOR counts and PCNA(PC10) scores are reliable markers of the proliferative activity of pharyngeal carcinoma in small, routinely processed biopsies, in which they can allow simultaneous evaluation of the histology and tumour cell kinetics.

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.