Collagen (XI) alpha-1 chain is an independent prognostic factor in breast ductal carcinoma in situ.

ABSTRACT

Collagen11A1 (COL11A1) is a fibrillary type collagen constituting a minor component of the extracellular matrix and plays role in tissue tensile strength. Overexpression of COL11A1 expression is associated with aggressive behavior and poor outcome in several human malignancies. In this study, we evaluated the association between COL11A1 expression and clinicopathological parameters of the breast ductal carcinoma in situ (DCIS) and its prognostic value. COL11A1 protein expression was assessed immunohistochemically in a large well-characterized cohort of DCIS including pure (n = 776) and DCIS associated with invasive carcinoma (DCIS-mixed, n = 239). COL11A1 expression was assessed in tumor cells and surrounding stromal cells, and correlated with clinicopathological parameters, immunoprofile and disease outcome. In pure DCIS, high COL11A1 expression was observed in tumor cells and surrounding stromal cells in 25 and 13% of cases, respectively. Higher COL11A1 expression within the stromal cells was associated with hormone receptor negative, HER2 enriched and triple negative molecular subtypes and showed a positive linear correlation with proliferation index, dense tumor infiltrating lymphocytes and hypoxia-inducible factor 1 alpha. COL11A1 expression in tumor and stromal cells was significantly higher in DCIS associated with invasive carcinoma than in pure DCIS, and within the DCIS-mixed cohort, the invasive component showed higher COL11A1 expression than the DCIS component (all, p < 0.0001). Overexpression of stromal COL11A1 was an independent predictor of shorter local recurrence-free interval for all recurrences (HR = 13.2, 95% CI = 6.9-25.4, p < 0.0001) and for invasive recurrences (HR = 11.2, 95% CI = 4.9-25.8, p < 0.0001). When incorporated with other risk factors, stromal COL11A1 provided better patient risk stratification. DCIS with higher stromal COL11A1 expression showed poor outcome even with adjuvant radiotherapy management. In conclusion, overexpression of stromal COL11A1 is associated with invasive recurrence in DCIS and is a potential marker to predict the response to radiotherapy.