Immunoreactivity of proliferating cell nuclear antigen compared with bromodeoxyuridine incorporation in normal and neoplastic rat tissue

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Abstract
Monoclonal antibodies (MoAbs) against proliferating cell nuclear antigen (PCNA) represent a potentially useful tool for cell kinetic analysis of tumours. Because in paraffin‐embedded tissue the relationship between PCNA immu‐noreactivity and tumour cell proliferation is not well characterized, we have compared PCNA positivity as detected by the PC10 MoAb with the bromodeoxyuridine labelling index (BrdUrd‐LI) in two different transplantable hormone‐dependent rat mammary tumours. Together, these two tumour models (MCR‐83 and EMR‐86) cover a wide range of S‐phase fractions. Evaluating 31 methacarn‐fixed tumours, a strong but non‐linear relationship (r=0·98) was obtained. PCNA‐positive fractions were invariably higher than corresponding BrdUrd‐LIs and also higher than the estimated growth faction: growth fractions as determined by continuous BrdUrd labelling of the tumour and stromal cell population in EMR‐86 carcinomas were 12 and 26 percent lower than PCNA‐positive fractions, implying that a certain fraction of non‐cycling cells can also express PCNA. A dramatic disturbance in the relationship of PCNA positivity and the BrdUrd‐LI was observed in the EMR‐86 model after growth arrest induced by hormonal ablation: PCNA immu‐noreactivity remained detectable for at least 3 days, whereas the BrdUrd‐LI decreased almost immediately. In comparison, PCNA immunoreactivity persisted for a much shorter period in small intestinal cells that had stopped DNA replication when moving from the crypt towards the villus. It is concluded that although differences in PCNA expression exist between various tissues, PCNA as detected by the PC10 MoAb may be used in tumours as an operational marker for the growth fraction. However, this seems to be valid only under conditions of unperturbed growth.