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Showing papers on "Tumour heterogeneity published in 1991"


Journal ArticleDOI
TL;DR: The ability of semiquantitative PCNA grading to allow for intra-tumoural variation suggests it may have advantages over absolute counting, which is prone to sampling error when tumour heterogeneity is a major factor.
Abstract: A new monoclonal antibody to proliferating cell nuclear antigen (PCNA), PC10, which can be used on routinely processed tissue, was applied to 93 cases of gastric carcinoma. Significant intra-tumoural variation in staining occurred. In addition to a PCNA index (percentage of positive cells per 1000 tumour cells), a semiquantitative PCNA grading system was devised, based on estimates of less than or more than 50% of positive tumour cells in whole sections. Neither PCNA index nor PCNA grade showed any correlation with established histological variables, tumour stage, or the presence of lymph node metastases. No significant correlation was observed between PCNA index and S + G2M phase fraction measured by flow cytometric analysis. To analyse survival tumours with PCNA indices above and below the median level (41%) were compared. Those with a higher index tended to have a worse prognosis, but when PCNA grade was considered, it was found to have definite independent prognostic value, tumours of low grade surviving better than those of high grade. The ability of semiquantitative PCNA grading to allow for intra-tumoural variation suggests it may have advantages over absolute counting, which is prone to sampling error when tumour heterogeneity is a major factor. The prognostic value of PC10 staining in gastric carcinoma is therefore promising.

189 citations


Journal ArticleDOI
TL;DR: The concentration of phosphorus‐containing metabolites was determined in extracts of multiple samples from six human breast tumours and in samples from normal and inflamed breast tissue and one of the inflamed samples, which consisted predominantly of macrophages, contained high levels of such compounds.
Abstract: The concentration of phosphorus-containing metabolites was determined in extracts of multiple samples from six human breast tumours and in samples from normal and inflamed breast tissue. The degree of lymphoid infiltrate, necrotic fraction and tumour cell and normal tissue fraction were determined on sections taken from each of the tumour samples. In four of the tumours there was a very high degree of variation between samples in the absolute concentration of metabolites. Three of these tumours showed a high degree of intra-tumour variation in the distribution of tumour cells and of normal tissue. The other two tumours were relatively homogeneous with respect to both tumour cellularity and the distribution of phosphorus-containing metabolites. Samples from normal breast tissue was found to contain only low concentrations of phosphorus-containing metabolites. However one of the inflamed samples, which consisted predominantly of macrophages, contained high levels of such compounds. The effect of time delay between resection and freezing on the levels of metabolites in human breast tumours was also examined.

32 citations


Journal ArticleDOI
TL;DR: Serial image-localized 31P magnetic resonance spectroscopy studies were performed in nine patients with newly diagnosed non-Hodgkin's lymphoma during the early part of treatment with chemotherapy, finding an alkaline shift in tumour pHi may be an early metabolic marker of response to chemotherapy.
Abstract: Serial image-localized 31P magnetic resonance spectroscopy studies were performed in nine patients with newly diagnosed non-Hodgkin's lymphoma (NHL) during the early part of treatment with chemotherapy. The pre-treatment intracellular pH (pHi) of the tumours ranged from 6.97 to 7.61 for high-grade NHL (n = 3), and 7.16 to 7.39 for low-grade NHL (n = 5). A pH of 7.24 was recorded in a patient with intermediate-grade NHL. Slice-to-slice variation in tumour pHi in spectra obtained with a one-dimensional chemical shift imaging (1D-CSI) technique varied from zero to 0.5 pH units. The largest variation was seen in high-grade tumours. Slice-to-slice variation may reflect tumour heterogeneity. Alkaline shifts in tumour pHi of 0.14 to 0.45 pH units were seen in six patients following chemotherapy. Maximal change in tumour pH was related temporally to increases in the phosphodiester/beta-adenosine triphosphate ratio, and occurred before alterations in tumour size were documented. Cell death and necrosis may be associated with an alkaline shift in pHi due to cessation of H(+)-producing processes and release of basic components of proteins. An alkaline shift in tumour pHi may therefore be an early metabolic marker of response to chemotherapy.

17 citations


Journal ArticleDOI
TL;DR: DNA ploidy studies were carried out on Feulgen stained smears and cytocentrifuge preparations from 35 malignant tumours and four benign neoplasms using the CAS image analyser.
Abstract: DNA ploidy studies were carried out on Feulgen stained smears and cytocentrifuge preparations from 35 malignant tumours and four benign neoplasms using the CAS image analyser. The smears were prepared from scrapings from fresh tumour tissue whereas the cytocentrifuge preparations were prepared from single nuclear suspensions from paraffin-embedded cell blocks from the same tumour. Histograms obtained by image analysis of the tumour scrapes were compared with those obtained on the cytocentrifuge preparations. Concordant results were obtained in four benign tumours (100%) and 32 malignant tumours (91%). The results obtained by image analysis were also compared with results obtained by flow cytometry of the tumour tissue. Discordant results were obtained for three malignant tumours. Possible reasons for the discrepancy include sampling error, tumour heterogeneity and selective loss of cell populations during processing.

5 citations


Journal ArticleDOI
TL;DR: Ulastructural examination of paraffin embedded tumour tissue representing eosinophilic areas in 40 renal cell tumours showed all tumours diagnosed light microscopically as oncocytomas to be composed of cells containing abundant mitochondria, and preoperative subclassification of renalcell tumours based on small biopsy specimens is of limited value.
Abstract: Eosinophilic renal tumour cells are found in oncocytomas, granular cell carcinomas, clear cell carcinomas and in a recently defined entity known as "congeners of oncocytomas". Ultrastructural examination of paraffin embedded tumour tissue representing eosinophilic areas in 40 renal cell tumours was performed in order to characterize the different types of eosinophilic cells. The results showed all tumours diagnosed light microscopically as oncocytomas to be composed of cells containing abundant mitochondria. Similar cells were, however, also found in one case of a clear cell carcinoma and in one case diagnosed light microscopically as a "congener". Oncocytes may therefore be found as part of non-oncocytomas and there seems to be a gradual transition from oncocytes to other eosinophilic cells of renal cell carcinomas. Preoperative subclassification of renal cell tumours based on small biopsy specimens is thus of limited value.

5 citations