p53 as a potential predictive factor of response to chemotherapy: feasibility of p53 assessment using a functional test in yeast from trucut biopsies in breast cancer patients.
Bottom Line: Three samples out of 90 failed to give any p53 PCR products, probably because these samples contained almost entirely fibrous tissue.Of the 87 samples that could be tested, the incisional and trucut biopsies results were fully concordant in every case. p53 could be defined in 97% of patients by double trucut biopsy.Histological examination before p53 testing is essential to exclude cases where the p53 result may reflect only the status of the normal cells in the biopsy.
Affiliation: Département de Gynécologie Obstétrique, Hôpitaux Universitaires de Genève, Boulevard de la Cluse 32, CH-1211 Genève 14-Switzerland.Show MeSH
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Mentions: One critical parameter in the test is the background number of red colonies. This determines the maximum permissible contamination of tumour samples with genetically normal cells. Histological examination revealed that most samples contained little or no normal breast tissue, but all contained significant numbers of genetically normal cells, principally fibroblasts, inflammatory cells and endothelial cells. Samples frequently contained large fibrotic acellular regions, with tumour cells present in small islands. Precise estimation of the number or fraction of tumour cells is extremely difficult in such heterogeneous material. The observed distribution of red colonies was used to infer the real background with clinical samples. The causes of variation in the background include factors like RNA polymerase errors, splicing artefacts, reverse transcriptase errors, Pfu polymerase errors, variation in the amount of input RNA, gap repair cloning artefacts, recombination at the reporter locus and yeast genetic suppressors of leu2-3,112. If we assume that these occur essentially at random, we should see two superimposed distributions in the results: a normally distributed population derived from wild type samples, superimposed upon a flatter distribution derived from p53 mutant samples. The latter can take any value above background, depending on the amount of normal tissue in the sample. This is exactly what is observed. Figure 1Figure 1
Affiliation: Département de Gynécologie Obstétrique, Hôpitaux Universitaires de Genève, Boulevard de la Cluse 32, CH-1211 Genève 14-Switzerland.