Background: Estrogen and progesterone receptor assays (ER and PgR), thymidine labeling index (TLI), DNA flow cytometric measurements of DNA index (DNAI) and S-phase fraction (SPF), and in vitro clonogenic testing of drug sensitivity have been applied to breast carcinomas. Preliminary studies in our laboratory indicate that some breast carcinomas have different DNAIs in different geographic locations or intermingled in some locations, indicative of multiple stemlines. Therefore, any of the above studies performed on a single sample may not be representative of the entire tumor.
Specific Aims : Geographic characterization of 50 primary breast carinomas for DNAI, TLI, ER, PgR. The objectives are to determine: 1. The frequency of heterogeneity of the DNAI for high vs. low mean ER, mean PgR and mean TLI. 2. Whether samples with different DNAI have characteristically different levels of ER, PgR and TLI. 3. Whether heterogeneity can be predicted by TLI, SPF, ER, PgR, age of patient, size or histologic characteristics of the tumor. 4. Whether the DNAI influences propensity for axillary metastasis. 5. Establish correlations of image analysis with DNAI, SPF and TLI. Methodology: The neoplasm will be dissected from the breast and sampled systematically, and each axillary metastasis will be sampled. The number of samples for flow cytometry will vary from 3 for carcinomas with 1.5 cm diameter to 33 for 10 cm diameter with fewer samples for TLI and receptor assays. The specimens for flow cytometry will be cryopreserved for subsequent propidium iodide staining and flow microfluorimetry at 488 nm excitation. Fresh tissue slices will be incubated with tritiated thymidine in presence of 2'-deoxy-5-fluorouracil and hyperbaric oxygen prior to fixation, sectioning and autoradiography. Receptor assays will be done on cytosol by Scatchard plot with correction for nonspecific binding and isoform analysis by chromatography. Microscopic image analysis will be done by digital computer analysis. Data will be analyzed by computer using standard programs and statistical methods. Long-Term Objectives: 1. Improve evaluation of breast carcinoma patients by optimizing tumor sampling for various assays. 2. Provide basis for studies of relationships between tumor heterogeneity and sensitivity to hormones, cytotoxic agents and radiation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042154-03
Application #
2090606
Study Section
Pathology B Study Section (PTHB)
Project Start
1985-09-01
Project End
1988-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
St. Luke's Hospital
Department
Type
DUNS #
City
Chesterfield
State
MO
Country
United States
Zip Code
63017
Meyer, J S; Wittliff, J L (1991) Regional heterogeneity in breast carcinoma: thymidine labelling index, steroid hormone receptors, DNA ploidy. Int J Cancer 47:213-20
Hyder, S M; Wittliff, J L (1989) Detection of two high molecular weight hydrophobic forms of the human estrogen receptor. J Steroid Biochem 33:965-70
Hyder, S M; Wittliff, J L (1989) Separation of two molecular forms of human estrogen receptor by hydrophobic interaction chromatography. Gradient optimization and tissue comparison. J Chromatogr 476:455-66
Meyer, J S; Nauert, J; Koehm, S et al. (1989) Cell kinetics of human tumors by in vitro bromodeoxyuridine labeling. J Histochem Cytochem 37:1449-54
Hyder, S M; Wittliff, J L (1988) High-performance hydrophobic interaction chromatography as a means of identifying estrogen receptors expressing different binding domains. J Chromatogr 444:225-37
Meyer, J S; Coplin, M D (1988) Thymidine labeling index, flow cytometric S-phase measurement, and DNA index in human tumors. Comparisons and correlations. Am J Clin Pathol 89:586-95
Meyer, J S; Province, M (1988) Proliferative index of breast carcinoma by thymidine labeling: prognostic power independent of stage, estrogen and progesterone receptors. Breast Cancer Res Treat 12:191-204
Ben-David, M; Wittliff, J L; Fekete, M et al. (1988) Lack of relationship between the levels of prolactin receptors and steroid receptors in women with breast cancer. Biomed Pharmacother 42:327-34
Hyder, S M; Sato, N; Hogancamp, W et al. (1988) High-performance hydrophobic interaction chromatography of estrogen receptors and magnesium dependent protein kinase(s): detection of two molecular forms of estrogen receptors in the presence and absence of sodium molybdate. J Steroid Biochem 29:197-206
Brandt, D W; Wittliff, J L (1987) Assessment of estrogen receptor-monoclonal antibody interaction by high-performance liquid chromatography. J Chromatogr 397:287-97

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