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Published on: November 5, 2020
Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma
Jeffrey R Infante1, Hiroyuki Matsubayashi, Norihiro Sato
1Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Purpose:
SPARC (secreted protein acidic and rich in cysteine) is a protein involved in cell matrix interactions, wound repair, and cell migration, and has been reported to inhibit cancer growth. SPARC undergoes epigenetic silencing in many pancreatic cancers, but stromal fibroblasts adjacent to infiltrating pancreatic adenocarcinomas frequently express SPARC. We evaluated the prognostic significance of tumor and peritumoral SPARC expression in patients with pancreatic adenocarcinoma.
Patients And Methods:
The expression patterns of SPARC were characterized by immunohistochemistry in 299 primary pancreatic ductal adenocarcinoma resection specimens from patients who underwent pancreaticoduodenectomy at Johns Hopkins Hospital (Baltimore, MD) between 1998 and 2003. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the mortality risk associated with the presence or absence of tumor SPARC and peritumoral SPARC status.
Results:
By Kaplan-Meier analysis, patients whose pancreatic cancer stromal fibroblasts expressed SPARC (median survival, 15 months) had a significantly worse prognosis than patients whose tumor stroma did not express SPARC (median survival, 30 months; log-rank P < .001). In contrast, the expression of SPARC in pancreatic cancer cells was not associated with prognosis (log-rank P = .13). Controlling for other prognostic factors (tumor size, positive lymph nodes, margin status, tumor grade, and age), the relative hazard for patients whose stroma expressed SPARC compared with those whose stroma did not was 1.89 (95% CI, 1.31 to 2.74); the expression of SPARC in pancreatic cancer cells remained unrelated to prognosis (relative hazard, 1.02; 95% CI, 0.73 to 1.42).
Conclusion:
The expression of SPARC by peritumoral fibroblasts portends a poorer prognosis for patients with pancreatic cancer.
Insights
Secreted protein acidic and rich in cysteine (SPARC) expression in pancreatic cancer stroma indicates a worse prognosis. SPARC in tumor cells, however, does not significantly impact patient survival outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Secreted protein acidic and rich in cysteine (SPARC) is implicated in cell matrix interactions, wound repair, and migration, and can inhibit cancer growth.
- SPARC is epigenetically silenced in many pancreatic cancers, yet is often expressed by stromal fibroblasts near tumors.
Purpose of the Study:
- To investigate the prognostic significance of tumor and peritumoral SPARC expression in pancreatic adenocarcinoma patients.
Main Methods:
- Immunohistochemistry was used to analyze SPARC expression in 299 pancreatic ductal adenocarcinoma resection specimens.
- Kaplan-Meier analysis and Cox proportional hazards regression assessed mortality risk associated with SPARC expression in tumor and stromal cells.
Main Results:
- Patients with SPARC-expressing stromal fibroblasts had significantly shorter median survival (15 months) compared to those without (30 months; P < .001).
- SPARC expression in pancreatic cancer cells was not associated with prognosis (log-rank P = .13).
- Adjusted analysis confirmed that stromal SPARC expression (hazard ratio, 1.89) predicted poorer prognosis, while tumor SPARC expression did not (hazard ratio, 1.02).
Conclusions:
- Peritumoral fibroblast SPARC expression is a significant indicator of a poorer prognosis in pancreatic cancer patients.
