DNA in situ sensitivity to denaturation as a marker of human breast tumors Journal Article
| Authors: | Kunicka, J. E.; Olszewski, W.; Rosen, P. P.; Kimmel, M.; Melamed, M. R.; Darzynkiewicz, Z. |
| Article Title: | DNA in situ sensitivity to denaturation as a marker of human breast tumors |
| Abstract: | DNA content and in situ sensitivity to denaturation were analyzed by flow cytometry of individual cell nuclei isolated from 40 breast carcinomas, nine fibroadenomas, and 14 samples of normal breast tissue. The extent of DNA denaturation induced by acid was expressed as αt, which represents the fraction of DNA staining metachromatically red with the fluorochrome acridine orange. In all cases of normal breast tissue DNA was very sensitive to denaturation and the frequency distribution of αt, values was unimodal with over 90% of cells having α, above 0.6. All fibroadenomas were diploid; four had unimodal α, as in normal tissue and five had a bimodal distribution with an additional peak below 0.6. Twenty-seven adenocarcinomas (67%) had a DNA index above 1.0; of these 24 had bimodal α, distributions. Among 13 diploid carcinomas 10 had bimodal aαt distributions. Statistically significant differences were observed in αt, distributions of normal versus tumor breast tissue (P < 0.005). In normal tissue and in all tumors a predominant proportion of cells with S and G2 + M DNA content were characterized by DNA resistant to denaturation (αt below 0.6). Of interest, the diploid cells from aneuploid tumors which may represent reactive host cells often displayed bimodal distributions of αt. These results may be interpreted in light of earlier studies demonstrating increased resistance of DNA to denaturation in diffuse chromatin of proliferating and/or transcriptionally active cells, and greater sensitivity to denaturation of DNA in condensed chromatin of quiescent cells. Thus, the presence of the second peaks representing cells with low αt, values in breast tumors may indicate a high proportion of proliferating cells, whereas high αt populations may represent quiescent and differentiating (condensed chromatin) or dying (pycnotic nuclei) cells. It is likely that the low αt, diploid cells detected in aneuploid tumors may represent the reactive (transcriptionally active and/or proliferating) infiltrating host cells (i.e., lymphocytes, monocytes) whose presence may also be of prognostic value. The data suggest that a DNA denaturability assay may be useful to characterize tumor and infiltrating host cell populations. © 1989, American Association for Cancer Research. All rights reserved. |
| Keywords: | adult; clinical article; aged; human cell; flow cytometry; animal; breast; tumor markers, biological; breast neoplasms; tumor marker; dna; luminescence; dogs; breast tumor; dna, neoplasm; carcinoma; histochemistry; nucleic acid denaturation; cell nucleus; acridine orange; cytochemistry; dna denaturation; adenofibroma; middle age; human; female; priority journal; article; support, u.s. gov't, p.h.s. |
| Journal Title: | Cancer Research |
| Volume: | 49 |
| Issue: | 22 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1989-11-15 |
| Start Page: | 6347 |
| End Page: | 6351 |
| Language: | English |
| PUBMED: | 2804980 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 14 April 2020 -- Source: Scopus |
Citation Impact
MSK Authors
Related MSK Work