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.

Expression of Cysteine-Rich Secreted Acidic Protein in Multiple Myeloma and Its Effect on the Biological Behavior of Cancer Cells

“…The secreted protein acidic and rich in cysteine (SPARC) is a secreted protein whose physiological function is related to tissue cell growth and development and tissue cell remodeling and repair [ 8 , 9 ]. Recent studies had shown that SPARC was involved in tumor occurrence, invasion, metastasis, angiogenesis, and inflammation [ 10 ].…”

SPARC suppresses lymph node metastasis by regulating the expression of VEGFs in ovarian carcinoma

“…Tumor metastasis to regional lymph nodes is often regarded as the first step of tumor dissemination, which precedes the metastasis of the vascular system and is seen as a major prognostic indicator of tumor progression. SPARC is a calciumbinding protein that not only competitively binds to the cell membrane surface growth factor receptor but also binds to several residents of ECM to influence cell proliferation, adhesion, migration, matrix degradation and angiogenesis (15,16). Studies have shown that SPARC plays different roles in many types of tumors including ovarian cancer and SPARC either lowly or highly expressed in ovarian cancer (17)(18)(19).…”

B7-H3 and B7-H4 Expression in Breast Cancer and Their Association with Clinicopathological Variables and T Cell Infiltration

“…Analysis of RNAscope amplification was performed semi-quantitatively as follows: 0, no staining or <1 dot/10 cells, 40×; 1, 1–3 dots/cell, 20–40×; 2, 4–10 dots/cell, 20–40×; 3, >10 dots/cell with <10% of positive cells having dot clusters visible at 20×; 4, >10 dots/cell with >10% of positive cells having dot clusters at 20× [30, 31]. Slides with a PPIB score of 2 or greater and DapB background score of 1 or less were considered to have passed the criteria for quality assessment of tissue mRNA and were included for analyzing B7-H3 and B7-H4 mRNA expression levels.…”