Visualization of collagen morphological changes in transition from tumor to normal tissue in breast cancer by multiphoton microscopy

The tumor microenvironment is now recognized as an important participant of tumor progression. As the most abundant extracellular matrix component in tumor microenvironment, collagen plays an important role in tumor development. The imaging study of collagen morphological characteristics in tumor microenvironment is of great significance for understanding the state of tumor. Multiphoton microscopy (MPM) based on second harmonic generation (SHG) and two-photon excitation fluorescence (TPEF) can be used to monitor the morphological changes of biological tissues without labeling. In this study, MPM was used to perform label-free imaging of the tumor border, the transition zone near the tumor, and the normal tissue away from the tumor sequentially from the center of the tumor in early invasive breast cancer samples. We found that collagen morphology varies significantly in different regions of breast cancer tumor tissue. The collagen content was further quantified and the results showed that the collagen content was significantly different in these three regions. The study of collagen remodeling around tumors may provide a new basis for optimal negative margin width of breast-conserving surgery and a new perspective for understanding tumor metastasis.