title: In phyllodes tumors of the breast expression of SPARC (osteonectin/BM40) mRNA by in situ hybridization correlates with protein expression by immunohistochemistry and is associated with tumor progression.
abstract: Secreted protein acidic and rich in cysteine (SPARC) plays an essential role in tumor invasion and metastasis. The present work was undertaken to detect expression of SPARC mRNA in phyllodes tumors (PTs) and its association with SPARC protein expression. This study also evaluated expression of SPARC mRNA and its correlation between grade and clinical behavior of PTs. In addition, we assessed in PTs the association of expression of SPARC with that of matrix metalloproteinase (MMP)-2 and of MMP-9. SPARC mRNA expression was determined by RNAscope in situ hybridization (ISH) in 50 benign, 22 borderline, and 10 malignant PTs using a tissue microarray. Furthermore, we applied immunohistochemistry (IHC) to examine expression of SPARC, MMP-2, and MMP-9. SPARC mRNA appeared to be concentrated mainly in the stromal compartment of PTs. IHC staining patterns of SPARC protein showed concordance with SPARC mRNA ISH results. Stromal SPARC expression increased continuously as PTs progress from benign through borderline to malignant PTs, both at mRNA (using ISH) (P = 0.044) and protein level (using IHC) (P = 0.000). The recurrence percentage was higher in the stromal SPARC mRNA or protein-positive group than in the SPARC-negative group but this difference was not statistically significant. Stromal SPARC mRNA and protein expression was associated with PT grade and correlated with MMP-2 expression. These results indicate that SPARC-mediated degradation of the extracellular matrix, and its possible association with MMPs, might contribute to progression of PTs.
authors.affiliation: Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Nah Ihm
authors.initials: NI
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Ga-Eon
authors.initials: GE
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea. jshinlee@hanmail.net.|Department of Pathology, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-gun, Jeollanam-do, 519-809, Republic of Korea. jshinlee@hanmail.net.
authors.forename: Ji Shin
authors.identifier: http://orcid.org/0000-0002-0911-4587
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D015676:Osteonectin / Q000235:genetics* / Q000378:metabolism; D003557:Phyllodes Tumor / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015676:Osteonectin; C577241:SPARC protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Matrix metalloproteinases; Phyllodes tumor; Protein; SPARC; mRNA