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Abstract
Background. Maspin is a member of the serpin family of protease inhibitors whose function in colorectal cancer is not fully understood. The objective of this study was to determine whether level of maspin expression could have prognostic or predictive value in colorectal cancer.
Material and methods. Maspin expression was assessed using immunohistochemistry on tissue microarrays obtained from 380 patients with stage II and III colorectal cancer randomized to adjuvant chemotherapy with fluorouracil and levamisole (5-FU/Lev) or to surgery only (control), with scores (0–300) based on presence (0–100) and intensity (0–3) of maspin expression. Associations with disease-free survival (DFS), cancer-specific survival (CSS) and prognostic factors were determined.
Results. Maspin expression was predominantly nuclear and present in tumor tissue in 99% of the cases. No associations with clinicopathological factors were identified. In colon cancer patients receiving adjuvant chemotherapy, maspin expression level was significantly associated with CSS [HR 1.43 per 50 points increase in maspin score (p = 0.021)] in multivariate analyses, and a significant interaction between treatment status and maspin expression (p = 0.045) was found. Kaplan-Meier plots from colon cancer patients showed a significant treatment benefit in patients with low maspin expression, but not for individuals with medium/high expression. Level of maspin expression was not significantly related to clinical outcome in rectal cancer or in any of the control groups.
Conclusions. In patients with colon cancer a low nuclear maspin expression was an independent predictor of benefit from adjuvant chemotherapy with 5-FU/Lev. A prognostic value of maspin expression was not found in this material.
Acknowledgments
We thank Solveig Mjelstad Olafsrud and Christine Drengenes for excellent technical assistance, the Norwegian Gastrointestinal Cancer Group for sponsoring the original clinical study and Tore Wentzel-Larsen (Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway; Centre for Child and Adolescent Mental Health, Eastern and Southern Norway, Oslo, Norway; Centre for Violence and Traumatic Stress Studies, Oslo, Norway) for expert statistical advice.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Supplementary material available online
Supplementary Figure 1 and Table I–IV available online at: http://informahealthcare.com/doi/abs/10.3109/0284186X.2014.952386.