Collagen Alignment as a Predictor of Recurrence after Ductal Carcinoma In Situ

Abstract

Collagen fibers surrounding breast ducts may influence breast cancer progression. Syndecan-1 interacts with constituents in the extracellular matrix, including collagen fibers, and may contribute to cancer cell migration. Thus, the orientation of collagen fibers surrounding ductal carcinoma (DCIS) lesions and stromal syndecan-1 expression may predict recurrence. We evaluated collagen fiber alignment and syndecan-1 expression in 227 women diagnosed with DCIS in 1995 to 2006 followed through 2014 (median, 14.5 years; range, 0.7-17.6). Stromal collagen alignment was evaluated from diagnostic tissue slides using second harmonic generation microscopy and fiber analysis software. Univariate analysis was conducted using χ tests and ANOVA. The association between collagen alignment -scores, syndecan-1 staining intensity, and time to recurrence was evaluated using HRs and 95% confidence intervals (CIs). Greater fiber angles surrounding DCIS lesions, but not syndecan-1 staining intensity, were related to positive HER2 ( = 0.002) status, comedo necrosis ( = 0.03), and negative estrogen receptor ( = 0.002) and progesterone receptor ( = 0.02) status. Fiber angle distributions surrounding lesions included more angles closer to 90 degrees than normal ducts ( = 0.06). Collagen alignment -scores for DCIS lesions were positively related to recurrence (HR = 1.25; 95% CI, 0.84-1.87 for an interquartile range increase in average fiber angles). Although collagen alignment and stromal syndecan-1 expression did not predict recurrence, collagen fibers perpendicular to the duct perimeter were more frequent in DCIS lesions with features typical of poor prognosis. Follow-up studies are warranted to examine whether additional features of the collagen matrix may more strongly predict patient outcomes. .

A shift from membranous and stromal syndecan‐1 (CD138) expression to cytoplasmic CD138 expression is associated with poor prognosis in breast cancer

“…The same peritumoral and diffuse patterns of CD138 stroma staining as described in this study had earlier been reported by Stanley et al Either alone or in combination, these stroma patterns occurred in 58.1% of our cancers. This frequency is comparable to the findings of most of the earlier studies, which had described stromal staining in smaller cohorts in the range of 9% to 63% (Table S4). Seven of these eight studies had failed to show a prognostic role of stromal CD138 and one study on 80 patients found a significantly worse prognosis in patients with stromal CD138 staining than in those tumors without.…”

“…Possible explanations include growths inhibitory or yet unrecognized immune‐stimulatory effects of CD138. For example, an inhibitory effect of sSDC1 on cell proliferation had been reported from wound healing experiments in mice and from human MCF‐7 BCa cells . In addition, CD138 plays a role in plasma cell differentiation and represents a central component of the plasma cell membrane .…”

The role of collagen in cancer: from bench to bedside

“…MMP-1 COLI Regulated to facilitate melanoma cell growth and invasion [227,228] COLIV Regulated to foster breast cancer cell invasion in response to prolactin [229] MMP-2 COLI Modulating MMP-2 activation in osteosarcoma [230] COL4A2 Modulating MMP-2 activation and activity in liver cancer [231] COLI and COLIV Regulated by the knockdown of MMP-2 to induce cancer metastases [232,233] Collagen organization Regulated to enhance malignant glioma recurrence and resistance to vemurafenib [234,235] MMP carcinoma [166,167]. TACS-3 was shown to be driven by increased plasminogen activator inhibitor 1 via ERK signaling and promoted the migration of triple-negative breast cancer cells [168].…”

Bioinformatics analysis suggests that COL4A1 may play an important role in gastric carcinoma recurrence

“…It is vital to understand the molecular mechanisms of cancer recurrence. [6][7][8][9] Many genes have been found to regulate cancer recurrence.…”