title: Expression of autophagy-related proteins in phyllodes tumor.
abstract: Phyllodes tumors (PTs) are classified as fibroepithelial tumors and their histologic grade is determined primarily by the features of the stromal component. In this study, we examined the expression profiles of autophagy-related proteins in the stromal component of PTs and analyzed their clinical implications. We selected 204 human PT samples which were excised and diagnosed at Severance Hospital from 2000 to 2008 and created tissue microarray (TMA) blocks. Immunohistochemical assays for autophagy-related proteins (beclin-1, LC3A, LC3B, and p62) were then performed on these samples. The surgical specimens from higher grade PTs less frequently displayed cytoplasmic expression of beclin-1, LC3A, LC3B, and p62 in the stromal component (p<0.001). In univariate analysis, the following profiles were associated with shorter disease-free survival and overall survival: nuclear beclin-1 positivity in the stromal component (p=0.013 and p=0.044, respectively), LC3A positivity in the stromal component (p<0.001 and p<0.001, respectively), and p62 positivity in the stromal component (p=0.012 and p=0.004, respectively). In conclusion, we determined that increased activity of autophagy-related proteins correlated with a higher histologic grade and poorer prognosis in PTs. These results lead us to conclude that the autophagy activity of the stromal cells plays a key role in the progression of PTs.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Severance Hospital Seoul, South Korea.
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
authors.forename: Woo Hee
authors.initials: WH
authors.lastname: Jung
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D003557:Phyllodes Tumor / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D000071456:Sequestosome-1 Protein; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D014408:Biomarkers, Tumor; C477012:MAP1LC3A protein, human; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein
keywords: Breast; autophagy; phyllodes tumor