Ki‐67 derived proliferative activity in colorectal adenocarcinoma with prognostic correlations

Abstract

Cryostat sections from samples of 108 colorectal carcinomas were stained with the murine monoclonal antibody Ki-67, which is expressed in proliferating cells. Ki-67 immunoreactivity was assessed independently by two pathologists using a semi-quantitative method. There was excellent correlation between the two observers. Ten cases were assessed quantitatively by counting at least 2000 cells and there was a very good correlation between this method and the semi-quantitative method. The carcinomas showed a wide range of Ki-67 labelling, reflecting a variation in proliferative activity. The tumour labelling index ranged from 1 to 80 per cent positivity: there was also heterogeneity of labelling within many of the tumours. There was no correlation between Ki-67 derived proliferative score and known prognostic parameters, including Dukes stage, New Prognostic Classification grade, lymph node status, tumour differentiation, venous spread, invasive margin, lymphocytic infiltrate, and curative versus palliative surgery. Nevertheless, it is concluded that Ki-67 immunohistochemistry provides a reliable and reproducible method of assessment of proliferative activity in colorectal cancer. Ki-67 immunohistochemistry may have a clinical application in the selection of patients with colorectal cancers who might benefit from radiotherapy and/or chemotherapy, particularly those with unresectable or locally recurrent tumours.

Intra-tumoral heterogeneity of tumour potential doubling times (Tpot) in colorectal cancer

“…For example, this has previously been demonstrated with respect to tumour DNA content (Scott et al, 1987;Koha et al, 1990;Wersto et al, 1991;Hiddemann et al, 1986), S phase fraction (Lindmark et al, 1991;Kouri et al, 1990), and expression of Ki67, a marker of proliferation (Shepherd et al, 1988). In this study the degree of intra-tumoral heterogeneity present in tumour DNA content, expressed as the DNA index (DI) and IUdR related flow cytometric parameters (labelling index, LI; DNA synthesis time, T7; and Tp,,) have been assessed.…”

“…(Zamcheck et al, 1975;Leibowitz et al, 1976) Siracky, 1979), in vitro growth characteristics (Dexter et al, 1981;Kimball & Brattain, 1980) and in the kinetics of the tumours as demonstrated by the measurement of S phase fraction (Lindmark et al, 1991;Kouri et al, 1990) and Ki67 labelling (Shepherd et al, 1988) and the presence of multiple DNA stemlines measured by flow cytometry (Hiddemann et al, 1986 (Begg et al, 1988;Bennett et al, 1992) and breast carcinomas (Rew et al, 1992). Although there is a significant degree of intra-tumoral heterogeneity (ln(TpO,) CV 22%), it compares favourably with the amount of inter-tumoral variation present (ln(Tp,01) CV 63%), indicating the ability to identify individual tumour proliferation characteristics (Table II).…”

Systematic heterogeneity and prognostic significance of cell proliferation in colorectal cancer

“…In this respect, the most extensive studies concern DNA analyses, i.e. evaluation of ploidy (Hiddemann et al, 1986;Scott et al, 1987) and S-phase fraction (Quirke et al, 1985;Lindmark et al, 1991), but also to other proliferative parameters such as PCNA (Teixeira et al, 1994) and expression of Ki-67 (Shepherd et al, 1988). A few reports exist on the presence of intratumoral heterogeneity with respect to LI/IHC and T /IHC in renal cell carcinoma (Larsson et al, 1994) and to pot T /FCM in colorectal cancer (Wilson et al, 1993b).…”

“…Colorectal cancer show a marked intratumoral heterogeneity with respect to several parameters, such as DNA content (Koha et al, 1990) and histological differentiation (Jass et al, 1986), and to proliferative parameters, such as S-phase fraction (Lindmark et al, 1991), PCNA (Teixeira et al, 1994) and expression of Ki-67 (Shepherd et al, 1988). Wilson et al (1993b) used flow cytometry alone to measure T , and have also described intratumoral heteropot geneity in colorectal cancers.…”

An immunohistochemical assessment of cellular proliferation markers in head and neck squamous cell cancers

“…The Ki-67 monoclonal antibody recognises a nuclear antigen present in proliferating cells, but absent in resting cells (Gerdes et al, 1983). Since its original description by Gerdes et al (1983), Ki-67 antibody has been a valuable tool for estimating the proportion of proliferating cells in a number of tumour types (Gerdes et al, 1986;Shepherd et al, 1988). Gerdes' group has recently demonstrated a highly significant correlation between the proportion of Ki-67 positive cells and the histologic classification of lymphomas into high and low grade malignancies (Gerdes et al, 1984).…”