High α-SMA expression in the tumor stroma is associated with adverse clinical parameters in mismatch repair–proficient colorectal cancers only

Sculthorpe, Declan J.; Denton, Amy; Fadhil, Wakkas; Rusnita, Dewi; Ilyas, Mohammad; Mukherjee, Abhik

Abstract

Objectives: As mismatch repair status confers differential prognosis in colorectal cancers, this study aimed to determine associations of α–smooth muscle actin (α-SMA) protein expression in mismatch repair–proficient (pMMR) and mismatch repair–deficient (dMMR) colorectal tumors with clinicopathologic and prognostic features. Methods: Tissue microarrays from patients with colorectal cancer, immunostained with α-SMA, were assessed through digital image analysis. Total (n = 962), pMMR (n = 782), and dMMR (n = 156) stromal H-scores were assessed for associations with clinicopathologic and survival data. Results: Higher α-SMA expression was correlated with pMMR status (P = 5.2223 × 10–8). In the pMMR subgroup, higher α-SMA stromal expression at the tumor periphery was correlated with higher T stage (P = .002), perineural invasion (P = .038), infiltrative tumor edge (P = .01), involved nodal status (P = .036), metastases (P = .013), synchronous metastases (P = .007), recurrence (P = .004), and both 3-year and 5-year survival (P = .018). dMMR tumors showed no significant correlations with α-SMA staining. Conclusions: The findings highlight that immunostaining with α-SMA in pMMR colorectal tumors, especially at the tumor periphery, has the potential to identify patients with adverse prognostic features. Digital assessment of α-SMA may offer improved objectivity, accuracy, economy of time, and risk stratification for management.

Citation

Sculthorpe, D. J., Denton, A., Fadhil, W., Rusnita, D., Ilyas, M., & Mukherjee, A. (2025). High α-SMA expression in the tumor stroma is associated with adverse clinical parameters in mismatch repair–proficient colorectal cancers only. American Journal of Clinical Pathology, 163(3), 464-472. https://doi.org/10.1093/ajcp/aqae145

• Journal Article Type: Article
• Acceptance Date: Oct 1, 2024
• Online Publication Date: Nov 4, 2024
• Publication Date: 2025-03
• Deposit Date: Nov 27, 2024
• Publicly Available Date: Nov 28, 2024
• Journal: American Journal of Clinical Pathology
• Print ISSN: 1943-7722
• Electronic ISSN: 0002-9173
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 163
• Issue: 3
• Pages: 464-472
• DOI: https://doi.org/10.1093/ajcp/aqae145
• Public URL: https://nottingham-repository.worktribe.com/output/42477134
• Publisher URL: https://academic.oup.com/ajcp/article/163/3/464/7874925