Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases.
BACKGROUND
Assessment of receptors [estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)] is routinely carried out on primary tumour in order to select appropriate adjuvant therapy; the same analysis is not carried out on nodal metastases. Since de novo resistance to therapy is common, we quantified differences in receptor expression between primary and nodal disease in order to assess whether this might contribute to therapeutic resistance.


METHODS
A total of 385 patients with invasive primary breast carcinomas and paired lymph nodes (n = 211) were assessed for ER, PR and HER2 expression using quantitative immunofluorescence. Cut-points were defined by comparison with tumours scored by immunohistochemistry (IHC) and FISH. Differences in expression for each of the markers and molecular phenotype were analysed.


RESULTS
Quantitative receptor expression shows a wide dynamic range compared with IHC. Overall, 46.9% cases had disparate breast/node receptor status of at least one receptor. Many of the differences in expression between primary tumour and node are large magnitude (greater than fivefold) changes. Triple-negative phenotype changes in 23.1% of cases.


CONCLUSIONS
A significant number of patients show discordant quantitative expression of molecular markers between primary and nodal disease. Appropriately measured, lymph node receptor status could be a more accurate measurement for guiding adjuvant therapy, which requires testing in a clinical trial.
Edinburgh Breakthrough Research Unit and Division of Pathology, University of Edinburgh, Edinburgh, UK.
S J
SJ
Aitken
Edinburgh Breakthrough Research Unit and Division of Pathology, University of Edinburgh, Edinburgh, UK.
J S
JS
Thomas
Edinburgh Breakthrough Research Unit and Division of Pathology, University of Edinburgh, Edinburgh, UK.
S P
SP
Langdon
Edinburgh Breakthrough Research Unit and Division of Pathology, University of Edinburgh, Edinburgh, UK.
D J
DJ
Harrison
Edinburgh Breakthrough Research Unit and Division of Pathology, University of Edinburgh, Edinburgh, UK. Electronic address: d.faratian@ed.ac.uk.
D
D
Faratian
D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D016555:Matched-Pair Analysis; D009367:Neoplasm Staging / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000032:analysis* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000032:analysis* / Q000378:metabolism; D012107:Research Design; D047368:Tumor Burden
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human