Expression of LC3B and FIP200/Atg17 in brain metastases of breast cancer.

Publication Title

Journal of neuro-oncology

Authors

Nooshin Hashemi-Sadraei
Gaëlle M Müller-Greven
Fadi W Abdul-Karim
Ilya Ulasov, Center for Advanced Brain Tumor Research, Swedish Neuroscience Institute, James Tower, Suite 570, 550 17th Ave., Seattle, WA, 98122, USA.
Erinn Downs-Kelly
Monica E Burgett
Adam Lauko
Maha A Qadan
Robert J Weil
Manmeet S Ahluwalia
Lingling Du
Richard A Prayson
Samuel T Chao
Thomas G Budd
Jill Barnholtz-Sloan
Amy S Nowacki
Ruth A Keri
Candece L Gladson

Document Type

Article

Publication Date

8-9-2018

Keywords

Autophagy; Brain metastases of breast cancer; FIP200/Atg17; LC3; Recurrence; Survival; Adult; Aged; Biomarkers, Tumor/metabolism; Brain/metabolism; Brain/pathology; Brain Neoplasms/metabolism; Brain Neoplasms/mortality; Brain Neoplasms/secondary; Brain Neoplasms/therapy; Breast Neoplasms/metabolism; Breast Neoplasms/mortality; Breast Neoplasms/pathology; Breast Neoplasms/therapy; Carcinoma, Ductal, Breast/metabolism; Carcinoma, Ductal, Breast/mortality; Carcinoma, Ductal, Breast/pathology; Carcinoma, Ductal, Breast/therapy; Female; Gene Expression Regulation, Neoplastic; Humans; Meta-Analysis as Topic; Microtubule-Associated Proteins/metabolism; Middle Aged; Protein-Tyrosine Kinases/metabolism; RNA, Messenger/metabolism; Retrospective Studies

Abstract

BACKGROUND: Macroautophagy/autophagy is considered to play key roles in tumor cell evasion of therapy and establishment of metastases in breast cancer. High expression of LC3, a residual autophagy marker, in primary breast tumors has been associated with metastatic disease and poor outcome. FIP200/Atg17, a multi-functional pro-survival molecule required for autophagy, has been implicated in brain metastases in experimental models. However, expression of these proteins has not been examined in brain metastases from patients with breast cancer.

METHODS: In this retrospective study, specimens from 44 patients with brain metastases of infiltrating ductal carcinoma of the breast (IDC), unpaired samples from 52 patients with primary IDC (primary-BC) and 16 matched-paired samples were analyzed for LC3 puncta, expression of FIP200/Atg17, and p62 staining.

RESULTS: LC3-puncta

CONCLUSIONS: These results support assessments of precision medicine-guided targeting of autophagy in treatment of brain metastases in breast cancer patients.

Area of Special Interest

Neurosciences (Brain & Spine)

Area of Special Interest

Cancer

Specialty/Research Institute

Neurosciences

Specialty/Research Institute

Oncology