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Collagen Alignment as a Predictor of Recurrence after Ductal Carcinoma In Situ
Matthew W Conklin1,2, Ronald E Gangnon2,3,4, Brian L Sprague5
1Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, Wisconsin.
Summary
Collagen fiber orientation around ductal carcinoma in situ (DCIS) lesions, not syndecan-1, showed associations with poor prognostic markers. Fibers perpendicular to ducts were more common in aggressive DCIS, suggesting potential for future outcome prediction.
Area of Science:
- Oncology
- Biomaterials Science
- Cancer Biology
Background:
- The extracellular matrix, particularly collagen fibers, plays a role in breast cancer progression and metastasis.
- Syndecan-1, an extracellular matrix proteoglycan, may influence cancer cell migration by interacting with collagen.
- The orientation of collagen fibers and expression of syndecan-1 around ductal carcinoma in situ (DCIS) may predict recurrence risk.
Purpose of the Study:
- To investigate the association between collagen fiber alignment and syndecan-1 expression in DCIS lesions and their predictive value for recurrence.
- To determine if collagen fiber orientation correlates with known prognostic markers in DCIS.
Main Methods:
- Collagen fiber alignment and syndecan-1 expression were analyzed in 227 DCIS patient tissue samples using second harmonic generation microscopy and immunohistochemistry.
- Statistical analyses, including chi-squared tests, ANOVA, and Cox proportional hazards models, were used to assess associations with recurrence and clinical features.
- Follow-up data through 2014 was used to evaluate time to recurrence.
Main Results:
- Greater collagen fiber angles surrounding DCIS lesions were associated with HER2-positive status, comedo necrosis, and negative estrogen and progesterone receptor status.
- While syndecan-1 staining intensity did not predict recurrence, collagen alignment showed a positive relationship with recurrence risk (HR=1.25).
- Fiber angles closer to 90 degrees (perpendicular to the duct) were more frequent in DCIS lesions compared to normal ducts.
Conclusions:
- Collagen fiber alignment and stromal syndecan-1 expression did not significantly predict recurrence in this DCIS cohort.
- However, collagen fibers oriented perpendicularly to the duct perimeter were more prevalent in DCIS lesions exhibiting features associated with a poorer prognosis.
- Further research into other collagen matrix features is warranted to improve outcome prediction in DCIS.
