Evaluation of proliferation parameters in in vivo bromodeoxyuridine labelled lung cancers

Abstract

In a series of 44 bronchial biopsies from patients suspected of having endobronchial lung carcinoma, the validity of proliferating cell nuclear antigen (PCNA) and Ki67 antigen as proliferative indicators was evaluated in ethanol fixed, paraffin embedded tissue. The percentages of cells positive for these markers were compared to the in vivo bromodeoxyuridine (BrdU) labelling index. A good correlation was found between PCNA immunoreactivity and BrdU labelling index, while Ki67-antigen expression showed a significant relation with BrdU labelling index and with PCNA expression. All three parameters showed a trend towards similar values for the individual cases. Based on the fact that Ki67 antigen is expressed in all cycling cells, whereas replicon-associated PCNA and BrdU only reflect the S-phase fraction, the differences between Ki67-antigen scores on the one hand and BrdU and PCNA scores on the other were smaller than expected. In order to determine the degree of concordance between immunohistochemically and flow cytometrically detected proliferation variables, BrdU incorporation was measured using both methods in duplicate bronchial specimens. Discrepancies in labelling indices were observed predominantly in DNA diploid samples, with consistently lower values in the flow cytometrically analysed specimens. In tumour specimens with an aneuploid DNA content, flow cytometric determination of proliferative activity yielded results similar to those obtained by tissue section examination. We conclude that the scores for PCNA and Ki67 antigen, immunohistochemically detected in ethanol fixed, paraffin embedded tissue reflect functional proliferative activity.

Comparison of Proliferating Cell Nuclear Antigen Expression in Odontogenic Keratocyst and Ameloblastoma: An Immunohistochemical Study

“…In the previous studies, a linear correlation between the percentage of PCNA-positive cells and S + G2 + M or S phase fraction measured by flow cytometry was recorded [9,31]. Also found was a linear correlation between the percentages of PCNA-positive cells and BrdU-labelled cells [27]. These findings suggest that PCNA immunostaining may be used as a marker of cell proliferation in various tumours.…”

The Presence of Neural Stem Cells and Changes in Stem Cell-Like Activity With Age in Mouse Spiral Ganglion Cells In Vivo and In Vitro

“…Our results also showed the presence of a few number of proliferated cells in mice of ages 12 weeks and older as indicated by Ki-67 marker. It was reported that Ki-67 antigen is expressed in all cycling cells, whereas BrdU reflects only the S-phage cells [ 16 ]. Importantly, the amount of proliferative stem cell populations shown in the P1 and 2-week-old mice SGN-NSCs were higher than those seen in the 4-, 12-, and 24-week-old mice SGN-NSCs, which supports the idea that the SGN-NSC spheres derived at an early age in mice contain more mitotic stem cells than those in mice at a later age.…”

Prognostic values of proliferating cell nuclear antigen (PCNA) and Ki-67 for radiotherapy of oesophageal squamous cell carcinomas

“…Strong nuclear staining may reflect a replication-associated from of PCNA (Yu et al, 1995). In the studies where alcohol was used as a fixative, a good correlation between PCNA expression and BrdU labelling indices or the flow cytometrically determined S phase fraction is reported because the replication-associated from of PCNA remains in the cell after alcoholic fixation (Coltrera et al, 1993;Tinnemans et al, 1995). In a prospective study on PCNA staining, alcohol fixation may be better than formalin fixation.…”