Estrogen receptor protein (ERP) in multiple tumor specimens from individual patients with breast cancer

Rosen, Paul Peter; Menendez‐Botet, Celia J.; Urban, Jerome A.; Fracchia, Alfred A.; Schwartz, Morton K.

doi:10.1002/1097-0142(197705)39:5<2194::aid-cncr2820390537>3.0.co;2-y

Cited by 79 publications

(17 citation statements)

References 21 publications

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“…Extracts of one primary breast tumour (tumour 29, figure 3) contained no oestrogen receptor mRNA, yet a lymph node metastasis from the same tumour did. Similar disparities between the oestrogen receptor levels in primary tumours and lymph node metastases have been reported previously (Rosen et al, 1977), although the converse situation arises more frequently (Castagnetta et al, 1987). Such heterogeneity may also explain the objective response to antioestrogen therapy seen in a small proportion of apparently oestrogen receptor-negative tumours.…”

Section: Discussionsupporting

confidence: 73%

Measurement of oestrogen receptor mRNA levels in human breast tumours

Henry

Nicholson²,

Farndon³

et al. 1988

Br J Cancer

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Summary A sensitive single-stranded hybridisation probe for the oestrogen receptor mRNA was synthesised using T3 polymerase from oestrogen receptor cDNA cloned in the Bluescript vector. This probe was used to measure oestrogen receptor mRNA in total RNA extracted from breast tumours. Oestrogen receptor mRNA was detected in 41 of 47 (87%) tumours whereas cytosolic oestrogen receptor protein was detected in only 18 out of 39 (46%). There was a significant correlation between the levels of the oestrogen receptor, as measured by 3H-oestradiol binding, and the oestrogen receptor mRNA. Breast cancer has long been known to be oestrogen responsive and the expression of the oestrogen receptor in a proportion of tumours is well recognised (McGuire et al., 1975). Different studies find the proportion of breast tumours expressing oestrogen receptor to be variable, ranging from 60% to 80% (Hawkins, 1985). Most studies indicate that patients with oestrogen receptor-positive tumours have better disease-free, post-relapse and overall survival, compared to those with oestrogen-receptor negative tumours (reviewed by Hawkins, 1985). A higher proportion of oestrogen receptor-positive tumours respond to antioestrogen therapy: paradoxically, a small number of oestrogen receptor-negative tumours also respond (Desombre et al., 1978).A variety of technique' have been used to determine oestrogen receptor protein levels in breast tumours, including tritiated hexoestrol binding in vivo (Folca, 1961), sedimentation assays (Desombre et al., 1978), dextran-coated charcoal assays (Korenman & Dukes, 1970), radio-immunoassay (Thorpe, 1987 logically. RNA was also prepared from combined endometrium and myometrium from the uterus of a premenopausal woman. Patient age ranged from 24 to 95 years: 14 were less than 50 years old and considered to be premenopausal. RNA extractionRNA was extracted from the 47 tumour biopsies and the uterus using a modification of the method of Auffrey & Rougeon (1980). Tumours frozen in liquid nitrogen were reduced to a powder using a Braun mikro dismembrator. Tumour powder was transferred to a Corex centrifuge tube, suspended in 5ml of 3M LiCl, 6M urea, 0.5% SDS and 50mM sodium acetate (pH5.6) and the DNA was sheared with an Ultraturrax homogeniser. RNA was precipitated at 4°C for 18h and recovered by centrifugation at 10,OOOg for 20 min. The supernatant was discarded and the resultant pellet was washed in 3 ml of 3 M LiCl, 6 M urea and 50mM sodium acetate and recentrifuged at 10,000 g for 0 min. The pellet was then resuspended in 1.125ml lOmM Tris buffer pH 8.0, 0.2% SDS, at room temperature, Tris buffer pH 8.0 and EDTA were added to 0.1 M and 5mM, respectively in 1.25ml total volume and then extracted with phenol:chloroform (50:50) and chloroform:isoamyl alcohol (24:1). The organic phases were back extracted with 1.25 ml 100mM Tris pH9. Following the addition of 6.25ml 100% ethanol and 50 pl 5 M NaCl, RNA was precipitated at -20°C. After centrifugation, the pellet was washed in 70% cold ethanol, recentrifuged, dried...

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Section: Discussionsupporting

confidence: 73%

Measurement of oestrogen receptor mRNA levels in human breast tumours

Henry

Nicholson²,

Farndon³

et al. 1988

Br J Cancer

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“…These antigens were chosen, in part because they are routinely performed on diagnostic specimens, and also because their expression from place to place within individual breast cancers is regarded as significantly heterogeneous. (Brennan et al, 1979;Layfield et al, 1998;Rosen et al, 1977;van Netten et al, 1985). In our cohort the percentage of ER-, PR-, and HER2-positive cases, based on whole-section staining, was 68%, 56%, and 24%, respectively.…”

Section: Resultsmentioning

confidence: 55%

Validation of Tissue Microarray Technology in Breast Carcinoma

Camp

Charette

Rimm

2000

Laboratory Investigation

696

488

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SUMMARY:The recent development of tissue microarray technology has potentiated large-scale retrospective cohort studies using archival formalin-fixed, paraffin-embedded tissues. A major obstacle to broad acceptance of microarrays is that they reduce the amount of tissue analyzed from a whole tissue section to a disk, 0.6 mm in diameter, that may not be representative of the protein expression patterns of the entire tumor. In this study, we examine the number to disks required to adequately represent the expression of three common antigens in invasive breast carcinoma-estrogen receptor, progesterone receptor, and the Her2/neu oncogene-in 38 cases of invasive breast carcinoma. We compared the staining of 2 to 10 microarray disks and the whole tissue sections from which they were derived and determined that analysis of two disks is comparable to analysis of a whole tissue section in more than 95% of cases. To evaluate the potential for using archival tissue in such arrays, we created a breast cancer microarray of 8 to 11 cases from each decade beginning in 1932 to the present day and evaluated the antigenicity of these markers and others. This array demonstrates that many proteins retain their antigenicity for more than 60 years, thus validating their study on archival tissues. We conclude that the tissue microarray technique, with 2-fold redundancy, is a valuable and accurate method for analysis of protein expression in large archival cohorts. (Lab Invest 2000, 80:1943-1949.

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“…Investigations of OR and PgR in metastatic tissue other than pleural have been carried out [13][14][15][16][17][18][19][20][21][22][23][24]. In these studies, 28-182 breast cancer patients with metastatic disease and detected OR and PgR were analysed.…”

Section: Discussionmentioning

confidence: 99%

Medical thoracoscopy: hormone receptor content in pleural metastases due to breast cancer

Schwarz

Lübbert²,

Rahn³

et al. 2004

European Respiratory Journal

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Pleural metastases are common in the course of breast cancer, but, to date, the role of oestrogen receptor (OR) and progesterone receptor (PgR) content in metastatic tissue has been poorly evaluated.A series of 50 consecutive patients with a history of breast cancer (median age 64 yrs, range 40-86 yrs), which presented with pleural effusion and therefore underwent medical thoracoscopy, was analysed. Metastatic pleural involvement was histologically confirmed in all patients. The hormone receptor status of the pleural metastases was investigated using the immunohistochemical method in 49 and the biochemical method in 31 cases. The immunohistochemical test was performed using monoclonal antibodies. Biochemical analysis was performed on specimens quick-frozen in liquid nitrogen. OR and PgR were measured with the dextran-coated charcoal assay and Scatchard analysis.Immunohistochemical analysis yielded 29 OR-positive and 25 PgR-positive cases and biochemical analysis yielded 16 OR-positive and four PgR-positive cases, sometimes discrepant to hormone status of the primary breast cancer. Using a semiquantitative immunoreactive score, there was a significant association between receptor positivity and survival, but only for PgR positivity.Immunohistochemical and biochemical detection of hormone receptors (oestrogen and progesterone) in pleural metastases of breast cancer is feasible based on medical thoracoscopy as the method of choice, by which sufficient specimens may be obtained. The receptor status may enable a decision on antihormonal treatment. Whether a positive receptor status in pleural metastatic tissue is associated with a better prognosis remains to be confirmed.

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Estrogen receptor protein (ERP) in multiple tumor specimens from individual patients with breast cancer

Cited by 79 publications

References 21 publications

Measurement of oestrogen receptor mRNA levels in human breast tumours

Measurement of oestrogen receptor mRNA levels in human breast tumours

Validation of Tissue Microarray Technology in Breast Carcinoma

Medical thoracoscopy: hormone receptor content in pleural metastases due to breast cancer

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