title: The expression of succinate dehydrogenase in breast phyllodes tumor.
abstract: The purpose of this study is to investigate the expression of succinate dehydrogenase (SDH)A, SDHB, and HIF-1α in phyllodes tumors and the association with clinic-pathologic factors. Using tissue microarray (TMA) for 206 phyllodes tumor cases, we performed immunohistochemical stains for SDHA, SDHB, and HIF-1α and analyzed their expression in regard to clinicopathologic parameters of each case. The cases were comprised of 156 benign, 34 borderline, and 16 malignant phyllodes tumors. The expression of stromal SDHA and epithelial- and stromal- SDHB increased as the tumor progressed from benign to malignant (P⟨0.001). There were five stromal SDHA-negative cases and 31 stromal SDHB-negative cases. SDHB negativity was associated with a lower histologic grade (P=0.054) and lower stromal atypia (P=0.048). Univariate analysis revealed that a shorter disease free survival (DFS) was associated with stromal SDHB high-positivity (P=0.013) and a shorter overall survival (OS) was associated with high-positivity of stromal SDHA and SDHB (P⟨0.001 and P⟨0.001, respectively). The multivariate Cox analysis with the variables stromal cellularity, stromal atypia, stromal mitosis, stromal overgrowth, tumor margin, stromal SDHA expression, and stromal SDHB expression revealed that stromal overgrowth was associated with a shorter DFS (hazard ratio: 24.78, 95% CI: 3.126-196.5, P=0.002) and a shorter OS (hazard ratio: 176.7, 95% CI: 8.466-3691, P=0.001). In conclusion, Tumor grade is positively correlated with SDHA and SDHB expression in the tumor stroma in phyllodes tumors of the breast. This result may be attributed to the increased metabolic demand in high grade tumors.
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, South Korea.
authors.forename: Junjeong
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Do Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: WooHee
authors.initials: W
authors.lastname: Jung
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea. kjs1976@yuhs.ac.
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002648:Child; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D046228:Microarray Analysis; D008875:Middle Aged; D003557:Phyllodes Tumor / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D013385:Succinate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics*; D055815:Young Adult
chemical_list: D051793:Hypoxia-Inducible Factor 1; D007527:Isoenzymes; D013385:Succinate Dehydrogenase