Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer.
Although breast cancer is the second most common cause of central nervous system (CNS) metastases with a notable increase of incidence, only few studies on brain-metastasizing breast cancer are available. In this immunohistochemical and fluorescence in situ hybridization (FISH) study, metastases to the CNS (n=85) and primary breast cancers, with known involvement of the CNS (n=44) including paired primary and metastasized tumours (n=23), were investigated retrospectively for the expression of oestrogen- (ER) and progesterone- (PR) hormone receptors, Her-2/neu, epidermal growth factor receptor (EGFR), Ki-67, and cytokeratins (CKs) 5/14. The majority of brain metastases were steroid hormone receptor negative (ER 66%, PR 82%) corresponding to the findings in primary tumours with known involvement of the CNS (68% ER-negative, 75% PR-negative). The frequency of HER-2/neu-overexpressing or -amplified cancers was increased in both groups (34 and 32%, respectively). EGFR expression was more frequent in metastases (41%) than in primary tumours (16%). The proportions of cases with a basal phenotype were 26 and 30%, respectively. In paired primary tumours and metastases to the CNS, constancy of Her-2/neu status was observed in 87% of cases with only one sample turning Her-2/neu-negative and two samples acquiring overexpression/amplification in brain metastases. In contrast, steroid hormone receptors exhibited more frequently a loss of expression (17%) than a gain (9%) with 74% revealing a constant phenotype. We conclude that brain-metastasizing breast cancer belongs predominantly to the basal type or Her-2/neu type. Primary and metastatic tumours differ from each other only in a minority of cases, leading rather to a loss of steroid hormone receptors and to a gain of EGFR and Her-2/neu.
Gaedcke
Jochen
J
Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany.
Traub
Frank
F
Milde
Simone
S
Wilkens
Ludwig
L
Stan
Alexandru
A
Ostertag
Helmut
H
Christgen
Mathias
M
von Wasielewski
Reinhard
R
Kreipe
Hans H
HH
D001932:Brain Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000556:secondary; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D053547:Keratin-14 / Q000032:analysis; D053555:Keratin-5 / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D018295:Neoplasms, Basal Cell / Q000737:chemistry* / Q000235:genetics / Q000556:secondary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D046888:Tissue Array Analysis
D066246:ErbB Receptors; D053547:Keratin-14; D053555:Keratin-5; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C507540:KRT14 protein, human; C503940:KRT5 protein, human; C508053:ERBB2 protein, human