EVALUATION OF PROLIFERATION PARAMETERS IN IN-VIVO BROMODEOXYURIDINE LABELED LUNG-CANCERS

In a series of 44 bronchial biopsies from patients suspected of having endobronchial lung carcinoma, the validity of proliferating cell nucl ear antigen (PCNA) and Ki67 antigen as proliferative indicators was ev aluated in ethanol fixed, paraffin embedded tissue. The percentages of cells positive for these markers were compared to the in vivo bromode oxyuridine (BrdU) labelling index. A good correlation was found betwee n PCNA immunoreactivity and BrdU labelling index, while Ki67-antigen e xpression showed a significant relation with BrdU labelling index and with PCNA expression. All three parameters showed a trend towards simi lar values for the individual cases. Based on the fact that Ki67 antig en is expressed in all cycling cells, whereas replicon-associated PCNA and BrdU only reflect the S-phase fraction, the differences between K i67-antigen scores on the one hand and BrdU and PCNA scores on the oth er were smaller than expected. In order to determine the degree of con cordance between immunohistochemically and flow cytometrically detecte d proliferation variables, BrdU incorporation was measured using both methods in duplicate bronchial specimens. Discrepancies in labelling i ndices were observed predominantly in DNA diploid samples, with consis tently lower values in the flow cytometrically analysed specimens. In tumour specimens with an aneuploid DNA content, flow cytometric determ ination of proliferative activity yielded results similar to those obt ained by tissue section examination. We conclude that the scores for P CNA and Ki67 antigen, immunohistochemically detected in ethanol fixed, paraffin embedded tissue reflect functional proliferative activity.