Heterogeneous estrogen receptor levels detected via multiple microsamples from individual breast cancers

Netten, Johannes P. van; Algard, F. Thomas; Coy, Peter; Carlyle, Sheila J.; Brigden, Malcolm L.; Thornton, Kenneth R.; Peter, Stephanie; Fraser, T.Russell; To, M

doi:10.1002/1097-0142(19851015)56:8<2019::aid-cncr2820560822>3.0.co;2-4

Cited by 43 publications

(12 citation statements)

References 22 publications

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“…Interestingly, our results indicated that an extensive variance in 18 F-FES uptake can be present across positive lesions within individuals (coefficient of variance, 68% 6 4%). This heterogeneity matches findings of multiple biopsies from individual patients showing that a variety of ER levels can be present (30,31). Furthermore, 45% of the patients with a positive 18 F-FES PET finding had both 18 F-FES-positive and 18 F-FES-negative metastases.…”

Section: Discussionsupporting

confidence: 82%

PET Imaging of Estrogen Receptors as a Diagnostic Tool for Breast Cancer Patients Presenting with a Clinical Dilemma

Kruchten¹,

Glaudemans²,

Vries³

et al. 2012

J Nucl Med

143

136

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16a-18 F-fluoro-17b-estradiol ( 18 F-FES) is an estrogen receptor (ER)-specific PET tracer with various potential interesting applications. The precise contribution of this technique in current clinical practice, however, has yet to be determined. Therefore, the aim of this study was to evaluate the value of 18 F-FES PET in breast cancer patients presenting with a clinical dilemma. Methods: 18 F-FES PET examination could be requested by referring physicians for patients with a history of ER-positive breast cancer and the presence of a clinical dilemma despite complete standard work-up. All requests for 18 F-FES PET required a positive arbitration by a dedicated medical oncologist and nuclear medicine physician. The referring physician was asked to fill in validated questionnaires before, shortly after, and at more than 3 mo after 18 F-FES PET to determine indication, diagnostic value, and therapeutic consequences of 18 F-FES PET. To further validate 18 F-FES PET findings, 18 F-FES PET lesions were quantified and compared with centrally reviewed conventional imaging. Results: Thirty-three patients underwent 18 F-FES PET between December 2008 and October 2010. 18 F-FES PET was requested to evaluate equivocal lesions on conventional work-up (n 5 21), ER status in metastatic patients (n 5 10), and the origin of metastases (n 5 2). 18 F-FES-positive lesions were observed in 22 patients. 18 F-FES PET was especially sensitive for bone metastases, detecting 341 bone lesions, compared with 246 by conventional imaging. The sensitivity for liver metastases was poor, and quantification of 18 F-FES uptake in liver lesions was hampered by high physiologic background. 18 F-FES uptake was highly variable between all metastases (range of standardized uptake value, 1.20-18.81), and 45% of the patients with a positive 18 F-FES PET finding had both 18 F-FES-positive and 18 F-FES-negative metastases. 18 F-FES PET improved diagnostic understanding in 88% of the patients and led to therapy change in 48% of the patients. Conclusion: With the exception of liver metastases, whole-body imaging of ER expression with 18 F-FES PET can be a valuable additional diagnostic tool when standard work-up is inconclusive. 18 F-FES PET supported therapy decisions by improving diagnostic understanding and providing information on ER status of tumor lesions.

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Section: Discussionsupporting

confidence: 82%

PET Imaging of Estrogen Receptors as a Diagnostic Tool for Breast Cancer Patients Presenting with a Clinical Dilemma

Kruchten¹,

Glaudemans²,

Vries³

et al. 2012

J Nucl Med

143

136

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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: 57%

Validation of Tissue Microarray Technology in Breast Carcinoma

Camp

Charette

Rimm

2000

Laboratory Investigation

698

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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“…On a more speculative note, it is possible that expression in the majority of cells is suppressed by dominant cells expressing high levels of the protein. Heterogeneity of oestrogen receptor levels has been demonstrated biochemically in different areas of the same tumour (van Netten et al, 1985) and immunohistochemically, in different cells (King et al, 1985). Immunohistochemical staining of other oestrogen-regulated proteins such as progesterone receptor (Soomro & Shousha, 1990) pNR-2 immunohistochemical staining was significantly associated with positive oestrogen receptor status (defined by a 5 fmol mg-' cytosolic protein threshold in a dextran coated charcoal ligand binding assay).…”

Section: Discussionmentioning

confidence: 99%

pNR-2/pS2 immunohistochemical staining in breast cancer: correlation with prognostic factors and endocrine response

Henry

Nh²,

Uk³

et al. 1991

Br J Cancer

108

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Heterogeneous estrogen receptor levels detected via multiple microsamples from individual breast cancers

Cited by 43 publications

References 22 publications

PET Imaging of Estrogen Receptors as a Diagnostic Tool for Breast Cancer Patients Presenting with a Clinical Dilemma

PET Imaging of Estrogen Receptors as a Diagnostic Tool for Breast Cancer Patients Presenting with a Clinical Dilemma

Validation of Tissue Microarray Technology in Breast Carcinoma

pNR-2/pS2 immunohistochemical staining in breast cancer: correlation with prognostic factors and endocrine response

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