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

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.