Expression of Lipid Metabolism-Related Proteins in Metastatic Breast Cancer.
OBJECTIVE
The tumor biology of metastatic breast cancers differ according to the metastatic sites, and the features of cancer metabolism may also be different. The aim of this study is to investigate the expression of lipid metabolism-related proteins in metastatic breast cancer according to metastatic site and discuss the clinical significance thereof.


METHODS
Immunohistochemical staining for lipid metabolism-related proteins [fatty acid synthase (FASN), hormone-sensitive lipase (HSL), carnitine palmitoyltransferase IA (CPT-1A), acyl-CoA oxidase 1 (ACOX1), fatty acid binding protein 4 (FABP4,) and perilipin 1 (PLIN1)] was performed using a tissue microarray of 149 cases of metastatic breast cancer (bone metastasis = 39, brain metastasis = 37, liver metastasis = 21, and lung metastasis = 52).


RESULTS
The expression levels of ACOX1 (p = 0.009) and FASN (p = 0.007) varied significantly according to metastatic site, with the highest expression in brain metastasis and the lowest expression in liver metastasis. ACOX1 positivity (p = 0.005) and FASN positivity (p = 0.003) correlated with HER-2 positivity. The expression of FASN was significantly higher in HER-2 type breast cancer, and lower in luminal A and TNBC type breast cancer (p<0.001). Among lipid metabolism-related proteins, PLIN1 positivity was found to be an independent poor prognostic factor on multivariate analysis (Hazard ratio: 4.979, 95% CI: 1.054-22.59, p = 0.043).


CONCLUSIONS
Different expression levels of lipid metabolism-related proteins were observed according to metastatic site. The expression of ACOX1 and FASN was highest in brain metastasis. These results suggest that the metastatic site should be considered when using lipid metabolism inhibitors for targeted therapy.
Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
Yoon Yang
YY
Jung
Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
Hye Min
HM
Kim
Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
Ja Seung
JS
Koo
D042962:Acyl-CoA Oxidase / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002334:Carnitine O-Palmitoyltransferase / Q000096:biosynthesis / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D004967:Estrogens; D054890:Fatty Acid Synthase, Type I / Q000096:biosynthesis / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D053208:Kaplan-Meier Estimate; D050356:Lipid Metabolism / Q000235:genetics*; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D011374:Progesterone; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism
D042962:Acyl-CoA Oxidase; D002334:Carnitine O-Palmitoyltransferase; D002352:Carrier Proteins; D004967:Estrogens; D054890:Fatty Acid Synthase, Type I; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins; D011374:Progesterone; D018719:Erb-b2 Receptor Tyrosine Kinases; C493410:FABP4 protein, human; C000602978:PLIN1 protein, human; C518729:FASN protein, human; C508053:ERBB2 protein, human