PCNA Immunohistochemistry

The reliability of PCNA immunostaining has been questioned (Louis et al., 1991 Harrison et al., 1993 Figge et al., 1992). In fact, some studies have ruled out a prognostic significance for PCNA expression. The use of PCNA as a reliable marker of cell proliferation, 

TABLE 10.2. Recent Immunohistochemical Localization of PCNA in Various Carcinomas 

The reproducibility of PCNA immunostaining analysis can be improved by computer-assisted image analysis (Sallinen et al, 1994). This approach also improves the reproducibility of quantitation among observers. The effect of tumor heterogeneity is minimized through this protocol because large tissue areas can be analyzed. Moreover, compared with visual assessment, computer-assisted analysis is faster. However, even in the computerized 

In light of the above-mentioned limitations, it seems that Ki-67 is a more specific marker for cell proliferation than PCNA. This suggestion is strengthened by the observation that ependymal cells (which are unable to regenerate) are PCNA positive but Ki-67 negative (Funato et al., 1996). In view of the aforementioned and other factors known to influence PC 10 labeling of PCNA, it should not be accepted uncritically as a marker of cell proliferation in sections of paraffin-embedded tissues. 

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Many proliferation-associated antigens have been reported as clinically useful indicators of proliferative activity (1). Of these, the so-called proliferating cell nuclear antigen (PCNA) and Ki-67 have been identified as the most useful in both immunohistochemistry (see Chapter 27) and flow cytometry (FCM). PCNA is an auxiliary protein to DNA polymerase 8 (2,3) and is intimately associated with DNA replication, but also DNA repair (4,5). Ki-67 is a large protein associated with nuclear nonhistone proteins (6,7), and is expressed in all actively proliferating cells (8,9). Expression of these two proteins, in a cell population should equate to the growth fraction, i.e., the proportion of cells involved in an active cell cycle. However, there are apparent inconsistencies when these two proteins have been compared with one another (10) and with other methods of assessing cell proliferation (11). 

S-phase fraction or immunohistochemistry to study expression of proliferating cell nuclear antigen (PCNA) or Numerous studies have shown a good... 

Figure 8. Microphotograph of decalcified sections, double Fast-Red and DAB immunohistochemistry staining for osteopontin and PCNA, respectively. Picture shows A3 areas of actuator (on the left) and static control (on the right), evidencing much more extensive osteopontin labelling around actuator. Scale bar represents 100 pm.

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