Research article
Receptor conversion in distant breast cancer metastases
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* Corresponding author: Paul J van Diest p.j.vandiest@umcutrecht.nl
1 Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
2 Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
3 Department of Pathology, Medical Center Alkmaar, Wilhelminalaan 12, 1815 JD Alkmaar, The Netherlands
4 Department of Pathology, Medical Center Zaandam, Koningin Julianaplein 58, 1502 DV Zaandam, The Netherlands
5 Department of Pathology, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands
6 Department of Pathology, Canisius Wilhelmina Hospital, Weg door Jonkerbos 100, 6532 SZ Nijmegen, The Netherlands
7 Department of Pathology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
8 Laboratory for Pathology, Laan van Londen 1800, 3317 DA Dordrecht, The Netherlands
9 Department of Pathology, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
10 Department of Pathology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands
11 Department of Pathology, Diakonessenhuis, Bosboomstraat 1, 3582 KE Utrecht, The Netherlands
12 Department of Pathology, Free University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
13 Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
14 Department of Medical Oncology, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
Breast Cancer Research 2010, 12:R75 doi:10.1186/bcr2645
Published: 23 September 2010Abstract
Introduction
When breast cancer patients develop distant metastases, the choice of systemic treatment is usually based on tissue characteristics of the primary tumor as determined by immunohistochemistry (IHC) and/or molecular analysis. Several previous studies have shown that the immunophenotype of distant breast cancer metastases may be different from that of the primary tumor (receptor conversion), leading to inappropriate choice of systemic treatment. The studies published so far are however small and/or methodologically suboptimal. Therefore, definite conclusions that may change clinical practice could not yet be drawn. We therefore aimed to study receptor conversion for estrogen receptor alpha (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in a large group of distant (non-bone) breast cancer metastases by re-staining all primary tumors and metastases with current optimal immunohistochemical and in situ hybridization methods on full sections.
Methods
A total of 233 distant breast cancer metastases from different sites (76 skin, 63 liver, 43 lung, 44 brain and 7 gastro-intestinal) were IHC stained for ERα, PR and HER2, and expression was compared to that of the primary tumor. HER2 in situ hybridization (ISH) was done in cases of IHC conversion or when primary tumors or metastases showed an IHC 2+ result.
Results
Using a 10% threshold, receptor conversion by IHC for ERα, PR occurred in 10.3%, 30.0% of patients, respectively. In 10.7% of patients, conversion from ER+ or PR+ to ER-/PR- and in 3.4% from ER-/PR- to ER+ or PR+ was found. Using a 1% threshold, ERα and PR conversion rates were 15.1% and 32.6%. In 12.4% of patients conversion from ER+ or PR+ to ER-/PR-, and 8.2% from ER-/PR- to ER+ or PR+ occurred. HER2 conversion occurred in 5.2%. Of the 12 cases that showed HER2 conversion by IHC, 5 showed also conversion by ISH. One further case showed conversion by ISH, but not by IHC. Conversion was mainly from positive in the primary tumor to negative in the metastases for ERα and PR, while HER2 conversion occurred equally both ways. PR conversion occurred significantly more often in liver, brain and gastro-intestinal metastases.
Conclusions
Receptor conversion by immunohistochemistry in (non-bone) distant breast cancer metastases does occur, is relatively uncommon for ERα and HER2, and is more frequent for PR, especially in brain, liver and gastro-intestinal metastases.