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Expression of high affinity folate receptor in breast cancer brain metastasis.

ABSTRACT: High affinity folate receptor (HFR) can be overexpressed in breast cancer and is associated with poor prognosis, however the expression in breast cancer brain metastases (BCBM) is unknown. The aim of this study was to analyze the rate of HFR expression in BCBM and its role in the prognosis of this high-risk cohort. We analyzed 19 brain metastasis (BM) and 13 primary tumors (PT) from a total of 25 patients. HFR status was assessed by immunohistochemistry. Median follow-up was 4.2 years (range 0.6-18.5). HFR was positive in 4/19 BM (21.1%) and in 1/13 PT (7.7%). Positive samples had low H-scores (range 1-50). 56% of patients had apocrine differentiation. OS was similar between patients with positive HFR (median OS 48 months) and negative HFR (median OS 69 months) (P = 0.25); and between patients with apocrine differentiation (median OS 63 months) and those without apocrine differentiation (median OS 69 months) (P = 0.49). To the best of our knowledge, this is the first analysis of HFR expression in BCBM. While previous studies associated the presence of HFR with worse prognosis; in our cohort HFR was positive in only 21.1% of BM with low levels of positivity. Neither HFR nor apocrine features had impact in OS.

SUBMITTER: Leone JP

PROVIDER: S-EPMC4745802 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Expression of high affinity folate receptor in breast cancer brain metastasis.

Leone José Pablo JP Bhargava Rohit R Theisen Brian K BK Hamilton Ronald L RL Lee Adrian V AV Brufsky Adam M AM

Oncotarget 20151001 30

High affinity folate receptor (HFR) can be overexpressed in breast cancer and is associated with poor prognosis, however the expression in breast cancer brain metastases (BCBM) is unknown. The aim of this study was to analyze the rate of HFR expression in BCBM and its role in the prognosis of this high-risk cohort. We analyzed 19 brain metastasis (BM) and 13 primary tumors (PT) from a total of 25 patients. HFR status was assessed by immunohistochemistry. Median follow-up was 4.2 years (range 0.6 ...[more]

PMID: 26160847

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Project description:BackgroundBrain metastasis is an unsolved clinical problem in breast cancer patients due to its poor prognosis and high fatality rate. Although accumulating evidence has shown that some pan-histone deacetylase (HDAC) inhibitors can relieve breast cancer brain metastasis, the specific HDAC protein involved in this process is unclear. Thus, identifying a specific HDAC protein closely correlated with breast cancer brain metastasis will not only improve our understanding of the functions of the HDAC family but will also help develop a novel target for precision cancer therapy.MethodsImmunohistochemical staining of HDAC1, HDAC2, and HDAC3 in 161 samples from breast invasive ductal carcinoma patients, including 63 patients with brain metastasis, was performed using the standard streptavidin-peroxidase method. The relationships between HDAC1, HDAC2, and HDAC3 and overall survival/brain metastasis-free survival/post-brain metastatic survival were evaluated using Kaplan-Meier curves and Cox regression analyses.ResultsHDAC1, HDAC2, and cytoplasmic HDAC3 all displayed typical oncogenic characteristics and were independent prognostic factors for the overall survival of breast cancer patients. Only cytoplasmic HDAC3 was an independent prognostic factor for brain metastasis-free survival. Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumors, while nuclear expression was downregulated. The HDAC1, HDAC2, and HDAC3 expression levels in the brain metastases were not correlated with survival post-brain metastasis.ConclusionsOur studies first demonstrate a critical role for HDAC3 in the brain metastasis of breast cancer patients and it may serve as a promising therapeutic target for the vigorously developing field of precision medicine.Key pointsSignificant findings of the study Cytoplasmic HDAC3 is an independent prognostic factor for the overall survival and brain metastasis-free survival of breast cancer patients. What this study adds Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumours, while nuclear expression was downregulated.

Project description:Breast cancer is the most common malignancy among women worldwide, and the main cause of death in patients with breast cancer is metastasis. Metastasis to the central nervous system occurs in 10% to 16% of patients with metastatic breast cancer, and this rate has increased because of recent advancements in systemic chemotherapy. Because of the various treatments available for brain metastasis, accurate diagnosis and evaluation for treatment are important. Magnetic resonance imaging (MRI) is one of the most reliable preoperative examinations not only for diagnosis of metastatic brain tumors but also for estimation of the molecular characteristics of the tumor based on radiographic information such as the number of lesions, solid or ring enhancement, and cyst formation. Surgical resection continues to play an important role in patients with a limited number of brain metastases and a relatively good performance status. A single brain metastasis is a good indication for surgical treatment followed by radiation therapy to obtain longer survival. Surgical removal is also considered for two or more lesions if neurological symptoms are caused by brain lesions of >3 cm with a mass effect or associated hydrocephalus. Although maximal safe resection with minimal morbidity is ideal in the surgical treatment of brain tumors, supramarginal resection can be achieved in select cases. With respect to the resection technique, en bloc resection is generally recommended to avoid leptomeningeal dissemination induced by piecemeal resection. An operating microscope, neuronavigation, and intraoperative neurophysiological monitoring are essential in modern neurosurgical procedures, including tumor resection. More recently, supporting surgical instruments have been introduced. The use of endoscopic surgery has dramatically increased, especially for intraventricular lesions and in transsphenoidal surgery. An exoscope helps neurosurgeons to comfortably operate regardless of patient positioning or anatomy. A tubular retractor can prevent damage to the surrounding brain tissue during surgery and is a useful instrument in combination with both an endoscope and exoscope. Additionally, 5-aminolevulinic acid (5-ALA) is a promising reagent for photodynamic detection of residual tumor tissue. In the near future, novel treatment options such as high-intensity focused ultrasound (HIFU), laser interstitial thermal therapy (LITT), oncolytic virus therapy, and gene therapy will be introduced.

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Expression of high affinity folate receptor in breast cancer brain metastasis.

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Expression of high affinity folate receptor in breast cancer brain metastasis.

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