Evaluation Of Stroma Fibrosis In Cancer Tissues Using Multiphoton Microscopy

Fibrosis is a pathological process of producing fibrous connective tissue excessively in an organ or tissue. It had been reported that the fibroblasts and myofibroblasts synthesized the extracellular matrix and collagen. Moreover, the myofibroblasts might be cause of severe stromal fibrosis in tissue. During the proliferation and progression of cancer, the desmoplasia can evoke a fibrosis in the nearby healthy stroma in order to contribute the tumor invasion. As a prognosis indicator, stroma fibrosis in invasive ductal carcinoma (IDC) of the breast and the colorectal carcinoma had been analyzed to be associated with tumor recurrence, tumor metastasis and poorer survival rate. However, the examination of stromal fibrosis is overlooked not only because the routine pathological examinations seemed to focus more on tumor staging and precise surgical margins, but also the lack of efficient diagnostic methods with high resolution in revealing the microstructure of the fibrotic tissues. Multiphoton microscopy imaging based on two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) has been recently employed for microscopic examination of unstained tissue. In this thesis, multiphoton microscopy (MPM) was used to image the fibrotic focus in invasive ductal carcinoma tissue of breast and stroma fibrosis in colorectal cancer in comparison with normal tissues. Three type of muscularis propria stromal fibrosis near the colorectal cancer infiltration edge were first investigated through the MPM imaging system by providing intercellular microstructural details in fresh tissue samples. Our approach also presents the capability of quantifying the extent of stromal fibrosis from both amount and orientation of collagen. By comparing with the pathology analysis, these results show that the MPM owns potential advantages in becoming a histological tool for detecting the stromal fibrosis and collecting prognosis evidences, which may guide subsequent therapy procedures for patients into good prognosis.