Measurement of cell proliferation in gastric carcinoma: comparative analysis of Ki-67 and proliferative cell nuclear antigen (PCNA)

Abstract

Immunostaining to identify nuclear antigens expressed throughout the cell cycle provides a convenient way of assessing proliferating kinetics in tumours. We studied proliferation activity of gastric carcinomas by Ki-67 and PCNA immunostaining and the two methods were compared. The mode of tissue preparation differed, fresh frozen for Ki-67 and formalin-fixed paraffin-embedded for PCNA. Immunostaining with avidin-biotin was used in both. The labelling index (LI) and a semi-quantitative grading of cell proliferation were assessed in both markers. Significant correlation was shown between LI and grading with either Ki-67 and PCNA. However, no correlation was found between PCNA and Ki-67. This lack of relationship between the two markers may be attributed to a number of factors. 1. The most likely is the marked inter- and intra-tumour heterogeneity of gastric carcinomas reflected in high standard deviation values. 2. Preparation of tissue and small size sampling with Ki-67. 3. Long life of PCNA leading to detection of cells that have recently left the cell cycle. 4. One may be observing deregulated expression of DNA as seen in certain tumours. PCNA offers the advantage of being applicable to archival material.

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“…The absence of a correlation between PCNA expression and BrdU incorporation in certain organs was in agreement with a number of previous reports in which no correlation was observed between anti-PCNA LI and other indices of proliferation (Jain et al, 1991;Yu et al, 1991;Leonardi et al, 1992;Rosa et al, 1992;Visakorpi, 1992).…”

Increased proliferative activity caused by loss of p21WAF1/CIP1 expression and its clinical significance in patients with early‐stage gastric carcinoma

“…In addition, Rosa et al found no correlation between the two indices, PCNA and Ki-67. 35 PCNA expression associated with DNA synthesis also is dependent on other factors; e.g., its synthesis can be induced by various growth factors. 36,37 Therefore, our findings may reflect not only the correlation between proliferative activity and p21 expression but also the fact that p21 interacts with PCNA and inhibits its action.…”

Prognostic Value of Proliferative Activity of Ovarian Carcinoma as Revealed by PCNA and AgNOR Analyses

“…4 2 -4 6 Particularly, the PCNA index showed a good correlation with the Ki-67 (MIB-1) index that is widely used to estimate proliferative activity in formalin-fixed paraffin-embedded tissues. [44][45][46] Some studies showed a lack of correlation between PCNA and Ki-67 indexes 20,47 that was attributed to several factors, including intertumoral and intratumoral heterogeneity, deregulated expression of PCNA, and prolonged half-life of PCNA leading to its persistence in some cells that are not actively dividing. 17,47 For the AgNOR count, it was shown that the mean AgNOR count differentiated between benign and malignant ovarian tumors but was of limited value in differentiating between borderline and malignant ovarian tumors.…”