Factors influencing the estimates of proliferative labelling indices in rectal cancer

Purpose. A detailed analysis was undertaken of some of the factors influencing the estimate of the labelling index (LI). Materials and methods: Thirty-three human rectal carcinomas were studied for their proliferative activity as measured by the fraction of cells labelled with a single injection of IdUrd 1-8 h before surgical resection. Adjacent specimens were stained both for histological examination and for flow cytometry (FCM) assessment of labelled nuclei. Results: Two major differences were found. The superficial parts of each tumour almost always had significantly higher LI values than the deep part (34 versus 21%), yielding an average LI of 27%. The flow cytometry average value was much lower (17%). This was partly due to the influence of diploid tumours. There was a marked heterogeneity in the values, both within tumours, between tumours and between techniques. The average LI for the whole group differs by a factor of three, depending on the method of assessment. Conclusions: All these values indicate a varying but rapid proliferative turnover of cells, surprisingly being more marked in the superficial region, i.e. the opposite from the proliferation pattern of the normal rectal mucosa. A biopsy, if taken from the superficial part of the tumour, would therefore be biased toward higher values. This has implications for biopsy sampling for cell kinetic analysis. Histological assessment avoids the contaminating effect of stromal cells, allows architectural arrangements to be detected and is presumably a more realistic representation of proliferative activity. (C) 1998 Elsevier Science Ireland Ltd.