A quality control study to assess the inter-laboratory variability of routine estrogen and progesterone receptor assays

Zava, David T.; Ballmoos, Aenn Wyler-Von; Goldhirsch, Aron; Roos, Werner; Takahashi, Atsuro; Eppenberger, Urs; Arrenbrecht, Stefan; Martz, G; Losa, Gabriele A.; Gómez, Fulgencio; Guelpa, C.

doi:10.1016/0277-5379(82)90068-2

Cited by 40 publications

(16 citation statements)

References 11 publications

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“…Special attention has been given to development of a standardized protocol [1,2], reproducibility [3], problems associated with analysis of low concentration of receptors [4], selection of reference material [5], and long-term variability [6]. Apart from this group, other national and international groups are operating to assure optimal performance of receptor assays [7][8][9][10]. In Europe, most of the national groups participate in the EORTC Receptor Group.…”

Section: Introductionmentioning

confidence: 99%

Comparison of ligand binding assay and enzyme immunoassay of oestrogen receptor in human breast cancer cytosols

Blankenstein¹

1990

Breast Cancer Res Tr

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Nine laboratories cooperating in the Receptor Study Group of the EORTC compared results of ligand binding assay supplemented with Scatchard plot analysis (LBA) and enzyme immunoassay (EIA) for the assessment of oestrogen receptors in 1665 breast cancer cytosols. An excellent agreement was observed between results of Scatchard plot analysis and EIA in each laboratory. Linear correlation coefficients of log-transformed data (log [(ER + 10)/10]) ranged from 0.839 to 0.977 (n = 52-373; P less than 0.001); Spearman's R ranged from 0.797 to 0.972 (P less than 0.001). Orthogonal regression analysis on log-transformed data revealed slopes of 0.794 to 1.141 and intercepts of -0.057 to 0.154 corresponding to -1.2 to 4.3 fmole/mg protein. Both assays compared equally well for pre- as well as postmenopausal patients, which confirms that occupied receptors are not extracted during the preparation of cytosol. The percentage discordance in the classification of tumours as ER positive or negative varied from 4.1 to 13.3 when a cut-off value of 10 fmol/mg protein was used, and from 1.4 to 7.5 at a cut-off level of 20. Considerable variations were observed in the actual receptor levels reported by each laboratory. Since these differences occurred in the results of both methods, they are attributed to differences in tissue handling. It is concluded that the ER-EIA is an excellent alternative to Scatchard plot analysis for the assay of oestrogen receptors. It is recommended, however, that laboratories performing assays on samples obtained from patients who are eligible for entrance in EORTC clinical trials and who wish to use the EIA should validate this assay against the Scatchard plot assay in their own setting.

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Section: Introductionmentioning

confidence: 99%

Comparison of ligand binding assay and enzyme immunoassay of oestrogen receptor in human breast cancer cytosols

Blankenstein¹

1990

Breast Cancer Res Tr

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“…Thus, the frequency of ER positivity is influenced if such samples occur frequently among those sent for analysis. This fact has been noted earlier [9,33], but it is rarely mentioned in clinical studies. In order to insure that only analyses on malignant tissue are considered to be valid in our institute, histological verification of tissue sent for receptor analysis is routinely performed on a formalin-fixed central portion of the biopsy received at the laboratory.…”

Section: Frequency Of Er Positivity In Patient Populationmentioning

confidence: 79%

“…Incubation time of binding: The binding kinetics for ER differ according to the concentrations of receptor and ligand used in the assay. Although the majority of laboratories now incubate ER binding assays for breast cancer tissue overnight to achieve binding equilibrium [9,12,16,18,21], shorter periods of incubation have previously been employed [9,36,37]. In our hands, an incubation period of 2 hr gave a binding result 50% lower than that attained after 20hrs of incubation.…”

Section: Differences In Methods Affecting the Entire Range Of Receptomentioning

confidence: 84%

“…Disparity in protein determinations of cytosol has previously been demonstrated to be a serious source of variation in receptor analyses [9][10][11]; however, not all observed variation in receptor analyses can be attributed to this source [12][13][14].…”

Section: Introductionmentioning

confidence: 98%

“…For unknown reasons, the PgR assay has remained the more difficult of the two assays to standardize [9,11,[15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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Steroid receptors in breast cancer: Sources of inter-laboratory variation in dextran-charcoal assays

Thorpe

1987

Breast Cancer Res Tr

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The presently recognized correlations between various clinical parameters and the concentrations of estrogen and progesterone receptors in breast cancer biopsies are largely based on receptor values obtained using the dextran-coated charcoal (DCC) method. This assay method is highly sensitive to slight changes in assay protocol, and differences in assay methodology may account for the wide variation in proportions of receptor positive patients reported by different centers. A survey of various aspects of the assay method that may lead to reproducible, systematic differences in concentrations of receptor levels is presented; and methods of compensating for or correcting these potential differences are discussed. The following aspects are considered: a) constitution of biopsy tissue, b) method of tissue homogenization, c) absorption of ligands to surfaces, d) inclusion of molybdate in the assay buffer, e) composition of the DCC slurry, and f) handling of samples for liquid scintillation counting. Differences in methods used to homogenize tissue in Europe and the U.S.A. may account for differences observed in the correlation of DCC assay results obtained using the recently-introduced monoclonal ER-EIA technique.

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The predictive value of estrogen and progesterone receptors' concentrations on the clinical behavior of breast cancer in women °clinical correlation on 547 patients

Vollenweider-Zerargui

Barrelet

Wong

et al. 1986

Cancer

129

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The aims of this study were as follows: to confirm that the presence of estrogen (ER) and progesterone (PgR) receptors is an indicator of clinical behavior of human breast cancer independent of other known prognostic factors; to seek clinical correlates of those receptor values that best predict the overall disease evolution; and to determine the relative prognostic importance of PgR versus ER. The clinical records of 547 patients, the follow-up of some extending to 6 years, were analyzed in retrospect. Patients were placed into one of four disease stages and also in three groups according to the degree of axillary node involvement. In each group the prognostic value of receptors for patient survival, disease-free interval and, in case of metastasis or local recurrence, the response to endocrine treatment or chemotherapy were studied. The break point in the spectrum of receptor concentrations with regard to survival, disease-free interval, and response to treatment was greater than or equal to 20 for ER+, greater than or equal to 15 for PgR+, and less than 5 for both ER- and PgR- reported in fmol/mg protein. Survival and disease-free interval showed positive correlations with ER and PgR (P less than 0.001-less than 0.0003). When disease stage or node involvement were considered, these correlations were found essentially in Stage II and node involvement in more than three nodes, where patients had longer survival and disease-free interval if ER and PgR were positive (P less than 0.05-less than 0.0003). Estrogen receptor was a more sensitive prognostic indicator than PgR, and the combination ER+/PgR+ showed a correlation equivalent to ER+/PgR-. The correct prediction percentages of the response of patients to endocrine treatment were 77% if ER+, 69% if PgR+, and 79% if both ER+ and PgR+. However, the correct prediction percentage of the response to chemotherapy was of 50%. These results show that ER and PgR are prognostic factors for survival and disease-free interval mainly on patients at Stage II and node involvement of greater than three, with ER demonstrating a better predictive value than PgR. The measurement of these receptors provides a prognostic index for response to endocrine therapy but is without value in predicting the response to chemotherapy.

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A quality control study to assess the inter-laboratory variability of routine estrogen and progesterone receptor assays

Cited by 40 publications

References 11 publications

Comparison of ligand binding assay and enzyme immunoassay of oestrogen receptor in human breast cancer cytosols

Comparison of ligand binding assay and enzyme immunoassay of oestrogen receptor in human breast cancer cytosols

Steroid receptors in breast cancer: Sources of inter-laboratory variation in dextran-charcoal assays

The predictive value of estrogen and progesterone receptors' concentrations on the clinical behavior of breast cancer in women °clinical correlation on 547 patients

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