Showing papers on "Tumour heterogeneity published in 1996"

A Survey of Models for Tumor-Immune System Dynamics

Abstract: A brief history of immunologic thinking - is it time for Yin and Yang? general aspects of modelling tumour growth and immune response tumour immune system interactions - the kinetic cellular theory tumour heterogeneity and growth control. (part contents)

Changes in expression of transforming growth factor beta mRNA isoforms in patients undergoing tamoxifen therapy

Abstract: Tumour was obtained from 37 patients with oestrogen receptor-positive breast cancer, before and during treatment with tamoxifen, and examined qualitatively and semi-qualitatively for mRNA of the three mammalian TGF-beta isoforms. Levels of TGF-beta isoforms were then correlated with tumour response to tamoxifen, as assessed by monthly ultrasound. A high incidence of expression by each isoform was found in tumour material taken both before and during treatment. Semiquantitative assessment of mRNA showed that in the majority of tumours, expression of TGF-beta s did not change markedly with treatment, i.e. beyond that which might have been caused by method reproducibility and tumour heterogeneity (variations of < 100% between pre- and post-treatment samples). In those displaying significant variation with treatment, expression of TGF-beta 1 and -beta 3 increased or decreased in equal numbers, whereas TGF-beta 2 expression tended to increase with treatment. Subdividing tumours by clinical response revealed no significant association between changes in expression of TGF-beta 1 and TGF-beta 3. There was, however, a significant correlation between changes in expression of TGF-beta 2 and response (P = 0.018). Thus, of 15 responding tumours displaying substantial changes, 11 showed an increase in TGF-beta 2 expression with treatment, whereas none of the non-responding tumours were associated with increased expression. While not providing evidence for a generalised increase in TGF-beta expression with tamoxifen treatment, the present study suggests that response to tamoxifen therapy may be associated with an increase in expression of specific TGF-beta isoforms in some, but not all, tumours.

Heterogeneity of mitotic activity in breast cancer.

Abstract: The aim of this study was to investigate to what extent mitotic activity index assessments are influenced by tumour heterogeneity Ten invasive breast carcinomas of varying size were completely embedded, yielding 2-7 paraffin blocks per tumour From each block, three H&E stained skip sections were cut and, in all sections, the mitotic activity index (MAI) and the mitoses per volume (M/V-)index were assessed Coefficients of variation were calculated for the three different sampling levels (tumours, blocks, sections) In addition we recorded in how many tumours threshold discrepancies (values on both sides of the prognostic thresholds) occurred Nested analysis of variance showed that most of the total variance occurred between the tumours Threshold discrepancies occurred in four (40%) and five tumours (50%) for mitotic activity index and the mitoses per volume index, respectively However, when grouping all sections from the same tumour and subjectively selecting the one showing the highest proliferation, the section with the highest mitotic activity was selected in nine of the 10 cases In the other single case a prognostically correct value was still obtained Thus, there is a noteworthy intra-tumour heterogeneity in mitotic activity in invasive breast cancer We therefore propose the need to take multiple blocks per tumour and carefully scan all sections for the highest proliferative area

Tumour heterogeneity: a problem in biopsy assessment of the proliferation index of oesophageal adenocarcinomas.

Abstract: Tumour heterogeneity may pose a problem when biopsy specimens are taken to measure proliferation (for example, in assessing response to therapy). Two “biopsy specimens” were taken from the centre and two from the edge of the luminal surface of 20 resected oesophageal adenocarcinomas. The proliferation index for each “biopsy specimen” was measured by counting Ki67 labelled nuclei in histological sections. The proliferation index was not associated with tumour differentiation or stage. There was site specific heterogeneity with a significant difference in proliferation index between the central (mean (SD) 36·4 (9·7)) and edge “biopsy specimens” (39·3 (9·9)). There was, however, a wide range of differences between pairs of “biopsy specimens” from both sites. In conclusion, if a tumour is to be sampled for measurement of the proliferation index before and after treatment, then the sequential biopsy specimens (preferably duplicated on each occasion) should be taken consistently from a leading edge of the lesion.

Quantitation of the allelic imbalance provides evidence on tumour heterogeneity: a hypothesis.

Abstract: The observation of loss of heterozygosity (LOH) in tumours represents a useful clue to the presence of tumour suppressor genes (TSGs). However, analysis of this phenomenon is often complicated by tumour heterogeneity and the presence of DNA from adjacent normal tissues. The present study suggests a quantitative approach for measurement of LOH which may help to distinguish between these possibilities and to provide clues for the heterogeneous process of tumour progression. We applied this methodology to a laryngeal tumour with LOH at markers D9S171, D9S157, D8S87 and THRA1 and found that LOH at D9S171 is the commonest aberration among the tumour cells, while LOH at the THRA1 marker is present in only a small subset of the tumour cells. It is likely that LOH at D9S171 occurs early in tumour development while LOH at the rest of the markers tested occurred later resulting in the generation of heterogeneous cell populations.