Collagen I fiber density increases in lymph node positive breast cancers: pilot study

Abstract

Abstract. Collagen I (Col1) fibers are a major structural component in the extracellular matrix of human breast cancers. In a preliminary pilot study, we explored the link between Col1 fiber density in primary human breast cancers and the occurrence of lymph node metastasis. Col1 fibers were detected by second harmonic generation (SHG) microscopy in primary human breast cancers from patients presenting with lymph node metastasis (LN þ ) versus those without lymph node metastasis (LN − ). Col1 fiber density, which was quantified using our in-house SHG image analysis software, was significantly higher in the primary human breast cancers of LN þ (fiber volume ¼ 29.22% AE 4.72%, inter-fiber distance ¼ 2.25 AE 0.45 μm) versus LN − (fiber volume ¼ 20.33%AE 5.56%, inter-fiber distance ¼ 2.88 AE 1.07 μm) patients. Texture analysis by evaluating the co-occurrence matrix and the Fourier transform of the Col1 fibers proved to be significantly different for the parameters of co-relation and energy, as well as aspect ratio and eccentricity, for LN þ versus LN − cases. We also demonstrated that tissue fixation and paraffin embedding had negligible effect on SHG Col1 fiber detection and quantification. High Col1 fiber density in primary breast tumors is associated with breast cancer metastasis and may serve as an imaging biomarker of metastasis.

COX-2 dependent regulation of mechanotransduction in human breast cancer cells

“…46 A high density of collagen 1 fibers in the ECM has been identified as a predictor of increased metastasis. 47,48 High collagen density has also been observed to increase tractions by breast cancer cells. 43 Increased metastasis associated with high collagen density may be mediated in part by this increased tractions.…”

Comparison of Picrosirius Red Staining With Second Harmonic Generation Imaging for the Quantification of Clinically Relevant Collagen Fiber Features in Histopathology Samples

“…3 Mechanistically, it is hypothesized that aligned collagen fibers form pathways that facilitate cancer cell migration away from the tumor and toward vasculature during the metastatic process. 3,4 While there is significant research work ongoing on the role of collagen in live, dynamic in vitro and in vivo animal models of a wide array of cancers, [5][6][7][8][9][10] many groups, including ours, are also focused on investigating the potential clinical utility of collagen properties in routinely fixed and processed human tissues. Toward clinical translation, it has already been shown that the detection of TACS in routine histopathological evaluation of breast cancer can serve as an optical biomarker and be predictive of disease recurrence and patient survival.…”

Simultaneous determination of the second-harmonic generation emission directionality and reduced scattering coefficient from three-dimensional imaging of thick tissues

“…It has been demonstrated that fixation does not alter the underlying fibrillar collagen structure and the resulting SHG properties [36][37][38] and primarily results in a slight volumetric shrinking. 39 For imaging, a single fascicle was pulled from the tail, and a small section was cut lengthwise, placed on a microscope slide with a drop of PBS, and sealed with a coverslip using nail polish (Sinful Colors).…”