Decalcification of Breast Cancer Bone Metastases with EDTA Does Not Affect ER, PR, and HER2 Results

Suzanne C. van Es, Bert van der Vegt, Frederike Bensch, Sophie Gerritse, Erik J. van Helden, Eline Boon, Lindsay Angus, Jelle Overbosch, Catharina W. Menke-van der Houven van Oordt, Henk M. Verheul, Carla M. L. van Herpen, Agnes Jager, Sjoukje F. Oosting, Elisabeth G. E. de Vries, Carolina P. Schröder

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

In metastatic breast cancer (MBC), expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) guides treatment selection. In case of bone-only metastatic disease, ER, PR, and HER2 status assessment may be hampered by decalcification. We aimed to determine the optimal decalcification method, and to study discordance of receptor expression between paired primary breast tumors and optimally decalcified bone metastases. First, decalcification was simulated using acetic acid, hydrochloric/formic acid, and EDTA on 12 primary breast carcinomas. ER, PR, and HER2 immunohistochemistry (IHC) and HER2 in situ hybridization (ISH) were assessed, before and after the 3 decalcification methods. EDTA was considered the optimal method, as it did not affect IHC and as ISH failed in only 1/16 cases. Hydrochloric/formic acid altered ER and PR results, and, with acetic acid and hydrochloric/formic acid, ISH failed in, respectively, 94% and 100%. Second, ER, PR, and HER2 IHC was performed in paired primary tumors and EDTA-decalcified bone metastases obtained from patients with first presentation of MBC. Clinically relevant discordance was defined as changed receptor status with treatment implications. Paired samples of 77 patients, participating in the IMPACT-MBC trial, were evaluable. Hormonal receptor expression change was clinically relevant in 6 patients (7.9%) and HER2 expression change in 1 patient (1.3%). This study shows that EDTA decalcification minimally affects receptor expression results. The incidence of clinically relevant discordance between the primary tumor and bone metastases is low. These findings support that bone biopsies can reliably be used to assess receptor status.
Original languageEnglish
JournalAmerican Journal of Surgical Pathology
DOIs
Publication statusPublished - 2019

Cite this

van Es, Suzanne C. ; van der Vegt, Bert ; Bensch, Frederike ; Gerritse, Sophie ; van Helden, Erik J. ; Boon, Eline ; Angus, Lindsay ; Overbosch, Jelle ; Menke-van der Houven van Oordt, Catharina W. ; Verheul, Henk M. ; van Herpen, Carla M. L. ; Jager, Agnes ; Oosting, Sjoukje F. ; de Vries, Elisabeth G. E. ; Schröder, Carolina P. / Decalcification of Breast Cancer Bone Metastases with EDTA Does Not Affect ER, PR, and HER2 Results. In: American Journal of Surgical Pathology. 2019.
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title = "Decalcification of Breast Cancer Bone Metastases with EDTA Does Not Affect ER, PR, and HER2 Results",
abstract = "In metastatic breast cancer (MBC), expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) guides treatment selection. In case of bone-only metastatic disease, ER, PR, and HER2 status assessment may be hampered by decalcification. We aimed to determine the optimal decalcification method, and to study discordance of receptor expression between paired primary breast tumors and optimally decalcified bone metastases. First, decalcification was simulated using acetic acid, hydrochloric/formic acid, and EDTA on 12 primary breast carcinomas. ER, PR, and HER2 immunohistochemistry (IHC) and HER2 in situ hybridization (ISH) were assessed, before and after the 3 decalcification methods. EDTA was considered the optimal method, as it did not affect IHC and as ISH failed in only 1/16 cases. Hydrochloric/formic acid altered ER and PR results, and, with acetic acid and hydrochloric/formic acid, ISH failed in, respectively, 94{\%} and 100{\%}. Second, ER, PR, and HER2 IHC was performed in paired primary tumors and EDTA-decalcified bone metastases obtained from patients with first presentation of MBC. Clinically relevant discordance was defined as changed receptor status with treatment implications. Paired samples of 77 patients, participating in the IMPACT-MBC trial, were evaluable. Hormonal receptor expression change was clinically relevant in 6 patients (7.9{\%}) and HER2 expression change in 1 patient (1.3{\%}). This study shows that EDTA decalcification minimally affects receptor expression results. The incidence of clinically relevant discordance between the primary tumor and bone metastases is low. These findings support that bone biopsies can reliably be used to assess receptor status.",
author = "{van Es}, {Suzanne C.} and {van der Vegt}, Bert and Frederike Bensch and Sophie Gerritse and {van Helden}, {Erik J.} and Eline Boon and Lindsay Angus and Jelle Overbosch and {Menke-van der Houven van Oordt}, {Catharina W.} and Verheul, {Henk M.} and {van Herpen}, {Carla M. L.} and Agnes Jager and Oosting, {Sjoukje F.} and {de Vries}, {Elisabeth G. E.} and Schr{\"o}der, {Carolina P.}",
year = "2019",
doi = "10.1097/PAS.0000000000001321",
language = "English",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",

}

Decalcification of Breast Cancer Bone Metastases with EDTA Does Not Affect ER, PR, and HER2 Results. / van Es, Suzanne C.; van der Vegt, Bert; Bensch, Frederike; Gerritse, Sophie; van Helden, Erik J.; Boon, Eline; Angus, Lindsay; Overbosch, Jelle; Menke-van der Houven van Oordt, Catharina W.; Verheul, Henk M.; van Herpen, Carla M. L.; Jager, Agnes; Oosting, Sjoukje F.; de Vries, Elisabeth G. E.; Schröder, Carolina P.

In: American Journal of Surgical Pathology, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Decalcification of Breast Cancer Bone Metastases with EDTA Does Not Affect ER, PR, and HER2 Results

AU - van Es, Suzanne C.

AU - van der Vegt, Bert

AU - Bensch, Frederike

AU - Gerritse, Sophie

AU - van Helden, Erik J.

AU - Boon, Eline

AU - Angus, Lindsay

AU - Overbosch, Jelle

AU - Menke-van der Houven van Oordt, Catharina W.

AU - Verheul, Henk M.

AU - van Herpen, Carla M. L.

AU - Jager, Agnes

AU - Oosting, Sjoukje F.

AU - de Vries, Elisabeth G. E.

AU - Schröder, Carolina P.

PY - 2019

Y1 - 2019

N2 - In metastatic breast cancer (MBC), expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) guides treatment selection. In case of bone-only metastatic disease, ER, PR, and HER2 status assessment may be hampered by decalcification. We aimed to determine the optimal decalcification method, and to study discordance of receptor expression between paired primary breast tumors and optimally decalcified bone metastases. First, decalcification was simulated using acetic acid, hydrochloric/formic acid, and EDTA on 12 primary breast carcinomas. ER, PR, and HER2 immunohistochemistry (IHC) and HER2 in situ hybridization (ISH) were assessed, before and after the 3 decalcification methods. EDTA was considered the optimal method, as it did not affect IHC and as ISH failed in only 1/16 cases. Hydrochloric/formic acid altered ER and PR results, and, with acetic acid and hydrochloric/formic acid, ISH failed in, respectively, 94% and 100%. Second, ER, PR, and HER2 IHC was performed in paired primary tumors and EDTA-decalcified bone metastases obtained from patients with first presentation of MBC. Clinically relevant discordance was defined as changed receptor status with treatment implications. Paired samples of 77 patients, participating in the IMPACT-MBC trial, were evaluable. Hormonal receptor expression change was clinically relevant in 6 patients (7.9%) and HER2 expression change in 1 patient (1.3%). This study shows that EDTA decalcification minimally affects receptor expression results. The incidence of clinically relevant discordance between the primary tumor and bone metastases is low. These findings support that bone biopsies can reliably be used to assess receptor status.

AB - In metastatic breast cancer (MBC), expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) guides treatment selection. In case of bone-only metastatic disease, ER, PR, and HER2 status assessment may be hampered by decalcification. We aimed to determine the optimal decalcification method, and to study discordance of receptor expression between paired primary breast tumors and optimally decalcified bone metastases. First, decalcification was simulated using acetic acid, hydrochloric/formic acid, and EDTA on 12 primary breast carcinomas. ER, PR, and HER2 immunohistochemistry (IHC) and HER2 in situ hybridization (ISH) were assessed, before and after the 3 decalcification methods. EDTA was considered the optimal method, as it did not affect IHC and as ISH failed in only 1/16 cases. Hydrochloric/formic acid altered ER and PR results, and, with acetic acid and hydrochloric/formic acid, ISH failed in, respectively, 94% and 100%. Second, ER, PR, and HER2 IHC was performed in paired primary tumors and EDTA-decalcified bone metastases obtained from patients with first presentation of MBC. Clinically relevant discordance was defined as changed receptor status with treatment implications. Paired samples of 77 patients, participating in the IMPACT-MBC trial, were evaluable. Hormonal receptor expression change was clinically relevant in 6 patients (7.9%) and HER2 expression change in 1 patient (1.3%). This study shows that EDTA decalcification minimally affects receptor expression results. The incidence of clinically relevant discordance between the primary tumor and bone metastases is low. These findings support that bone biopsies can reliably be used to assess receptor status.

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U2 - 10.1097/PAS.0000000000001321

DO - 10.1097/PAS.0000000000001321

M3 - Article

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

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