Progesterone receptors in routinely paraffin-embedded primary breast carcinomas and lymph node metastases

Müller‐Holzner, Elisabeth; Zeimet, Alain G.; Daxenbichler, Günter; Marth, Christian; Müller, Ludwig; Dapunt, O

doi:10.1007/bf00662400

Cited by 9 publications

(3 citation statements)

References 15 publications

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“…Of these positive studies, four 34,35,39,40 used frozen section immunohistochemistry, and the other three, which were done on archival tissue, used either KD 68 42 or noncommercial antibodies. 33,44 Similarly, four studies, 12,31,35,45 evaluated patients with advanced/metastatic disease, and three 12,31,35 showed a significant clinical benefit of hormonal therapy in patients with PRpositive tumors. All three studies employed the KD 68 antibody.…”

Section: Discussionmentioning

confidence: 99%

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

et al. 2004

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Progesterone receptor is a surrogate marker of estrogen receptor activity in breast cancer and its utility in helping predict clinical outcome has been established using biochemical assays. However, most laboratories worldwide have switched to immunohistochemistry to assess progesterone receptor, but unfortunately no validated immunohistochemical assay exists for progesterone receptor. The purpose of this study was to develop and validate an immunohistochemical assay for progesterone receptor in breast cancer. The assay was based on monoclonal antibody 1294 (DakoCytomation) and slides were scored microscopically using the 'Allred score' on a scale of 0-8. The assay was compared to ligand-binding assay in 1235 breast cancers, and a subset (n ¼ 362) that received only hormonal therapy was used to define a cutoff for progesterone receptorpositive. Clinical utility was validated in an independent set of samples (n ¼ 423) from a clinical trial randomizing premenopausal breast cancer patients to tamoxifen þ oophorectomy vs observation following surgery. A cutoff of 42 (corresponding to 41% positive cells) dichotomized patients with significantly better or worse clinical outcome (P ¼ 0.0014). Progesterone receptor by immunohistochemistry provided significantly better results than progesterone receptor by ligand-binding assay in predicting clinical outcome. In the clinical trial, a positive result in univariate analyses was associated with significantly improved disease-free and overall survival both in untreated (hazard ratios/P ¼ 0.656/0.060 and 0.479/0.005, respectively) and hormonally treated patients (hazard ratios/P ¼ 0.529/0.017 and 0.451/0.007, respectively). Positive progesterone receptor remained significant for improved disease-free and overall survival (hazard ratios/P ¼ 0.666/0.038 and 0.549/0.007, respectively) in multivariate analyses including the standard variables of tumor size, nodal status, treatment, histological grade, and HER-2/neu status. Estrogen and progesterone receptors are codependent variables and progesterone receptor was a weaker predictor of response to endocrine therapy than estrogen receptor when both were included in multivariate analysis. This is the first comprehensive study assessing the clinical usefulness of progesterone receptor by immunohistochemistry in archival tissue in breast cancer. Progesterone receptor assessed by immunohistochemistry provides useful information about clinical outcome and it is better than progesterone receptor measured by ligand-binding assay.

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Section: Discussionmentioning

confidence: 99%

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

et al. 2004

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“…More recent reports have overcome these limitations by using immunohistochemical determination of ER and PR, but the numbers examined are small. Nevertheless, it appears that in matched cases the receptor phenotype of the primary cancer is likely to be maintained in the recurrent tumour in the majority of cases (Kamby et al, 1989;Muller-Holzner et al, 1993;Kuukasjarvi et al, 1996). The more general question of whether certain receptor phenotypes are associated with greater likelihood of progression to metastasis is, therefore, important.…”

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confidence: 99%

Absence of progesterone receptor associated with secondary breast cancer in postmenopausal women

et al. 1999

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SummaryThe relationship between expression of receptors for oestrogen and progesterone (ER and PR) and disease progression in breast cancer was investigated by comparing immunocytochemical determinations of ER and PR in fine needle aspirates from primary and secondary breast tumours. Rates of receptor expression were significantly higher in primary than in secondary lesions: for ER 63.3% (n = 689) compared with 45.3% (n = 223), and for PR 53.7% (n = 443) compared with 33.1% (n = 121). The effect of menopausal status was examined by subdividing the patient cohort into those over or under the age of 50 years. In both instances, ER expression in secondary tumours was relatively low; however, only postmenopausal patients had significantly lower rates of PR expression in secondary tumours. Consistent with this, an increase in the ER+PR-profile in secondary tumours compared with primary cases from postmenopausal patients was seen, and in a multivariate analysis, a specific absence of PR expression in secondary tumours was revealed. Comparison of ER and PR expression in simultaneously sampled primary tumours and lymph node metastases from the same patient showed that receptor expression was stable with progression to a metastatic site as results were concordant for ER in 92% (n = 88) and PR in 93.8% of cases (n = 65). These results suggest that absence of PR expression in primary breast cancer is associated with disease progression and may be a marker of an aggressive tumour phenotype. Keywords: breast cancer; metastatic; receptors -oestrogen -progesterone 1564British Journal of Cancer (1999) 79(9/10), 1564-1571 © 1999 Cancer Research Campaign Article no. bjoc.1998 Received 14 April 1998 Revised 2 September 1998 Accepted 18 September 1998 Correspondence to: R Balleine numbers examined are small. Nevertheless, it appears that in matched cases the receptor phenotype of the primary cancer is likely to be maintained in the recurrent tumour in the majority of cases (Kamby et al, 1989;Muller-Holzner et al, 1993;Kuukasjarvi et al, 1996). The more general question of whether certain receptor phenotypes are associated with greater likelihood of progression to metastasis is, therefore, important.The purpose of this study was to determine, using immunocytochemical methods in a large cohort of primary and secondary breast cancers sampled by fine needle aspiration, the combined ER and PR phenotypes, to ask whether secondary lesions are more likely to be receptor-positive than negative and to determine whether a particular ER/PR phenotype predominated in secondary lesions. The profile of receptor expression in primary and secondary tumours in pre-and postmenopausal women is not known and has also been examined in this study. METHODS PatientsPatients were women who presented for diagnostic fine needle aspiration biopsies of breast tumours to the Department of Tissue Pathology at Westmead Hospital between 1986 and 1993. 'Primary' tumours were aspirates of lesions in the breast diagnosed as 'adenocarcinoma' or 'colloid carcinoma'....

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“…There is significantly less information concerning the value of immunohistochemical PgR assay procedures. There are only 11 studies available with a total of 2,578 patients, most performed on frozen sections and many employing the antibody KD68 (21, 24,28,[32][33][34][35][36][62][63][64]. The average frequency of positivity was 48%.…”

Section: Progesterone Receptor Antibodies: Clinical Correlatesmentioning

confidence: 99%

Steroid Hormone Receptor Immunohistochemistry in Breast Cancer: Past, Present, and Future

Pertschuk

Axiotis

1999

The Breast Journal

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This article reviews the development of steroid hormone receptor detection using the biochemical approach and the disadvantages inherent in these systems. The early history of methods for the in situ detection of receptors is related, culminating in the development of histologic immunoassays using monoclonal antibodies. Correlation of the latter with disease-free and overall survival and with clinical endocrine response are presented together with preliminary findings utilizing a new generation of antireceptor antibodies. Current problems with test scoring and interpretation are detailed with a section devoted to image analysis for assay quantification. Emphasis is placed on the fact that because so many different antibodies and tissue substrates have been employed in the past, these histologic receptor immunoassays cannot yet be considered to be fully validated. It is stressed that different laboratories must employ the same antibodies, substrates, detection systems and methods of scoring, and then correlate findings with measurable clinical end points. Only then can the assays be included in the brief list of approved breast cancer prognostic and predictive markers to eventually replace the routine biochemical methods of steroid receptor detection.

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Progesterone receptors in routinely paraffin-embedded primary breast carcinomas and lymph node metastases

Cited by 9 publications

References 15 publications

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

Absence of progesterone receptor associated with secondary breast cancer in postmenopausal women

Steroid Hormone Receptor Immunohistochemistry in Breast Cancer: Past, Present, and Future

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