title: Differential Site-Based Expression of Pentose Phosphate Pathway-Related Proteins among Breast Cancer Metastases.
abstract: Purpose. We aimed to investigate the expression of pentose phosphate pathway- (PPP-) related proteins in metastatic breast cancer and its relationship with clinicopathologic factors.Methods. Tissue samples from 126 metastatic breast cancers were included in a tissue microarray. Expression of PPP-related proteins [glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconolactonase (6PGL), 6-phosphogluconate dehydrogenase (6PGDH), and nuclear factor erythroid 2-related factor (NRF2)] was determined by immunohistochemistry.Results. G6PDH (p= 0.011) and cytoplasmic NRF2 (p= 0.001) showed the highest expression in brain metastases. Human epidermal growth factor receptor (HER-2) positivity was associated with G6PDH (p< 0.001) and cytoplasmic NRF2 (p= 0.015) positivity. A high Ki-67 labeling index (LI) was correlated with nuclear NRF2 positivity (p= 0.037), and HER-2-positive luminal B type was associated with G6PDH positivity (p= 0.001). On multivariate Cox analysis, independent risk factors of short overall survival were 6PGL positivity in bone metastasis (HR 4.180, 95% CI 1.160-15.06,p= 0.029) and low Ki-67 LI in lung metastasis (HR 11.853, 95% CI 1.841-76.30,p= 0.009).Conclusion. Differential expression of PPP-related proteins correlated with different prognoses and metastatic sites, with the highest expression in brain metastases, and could be a potential therapeutic target.
authors.affiliation: Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Republic of Korea.
authors.forename: Yoon Jin
authors.initials: YJ
authors.lastname: Cha
authors.affiliation: Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Republic of Korea.
authors.forename: Woo Hee
authors.initials: WH
authors.lastname: Jung
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
authors.forename: Ja Seung
authors.identifier: 0000-0003-4546-4709
authors.initials: JS
authors.lastname: Koo
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary; D001842:Bone and Bones / Q000473:pathology; D001932:Brain Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010427:Pentose Phosphate Pathway; D010641:Phenotype; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012307:Risk Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D002265:Carboxylic Ester Hydrolases; D019394:Ki-67 Antigen; D051267:NF-E2-Related Factor 2; D010734:Phosphogluconate Dehydrogenase; D018719:Erb-b2 Receptor Tyrosine Kinases; C495635:NFE2L2 protein, human; C508053:ERBB2 protein, human; C022363:6-phosphogluconolactonase