Monitoring morphological alterations during invasive ductal breast carcinoma progression using multiphoton microscopy

Abstract

Morphological alteration of cells and matrices is critical for tumor initiation and progression. Monitoring these alterations during tumor progression is vitally important for making real-time histological diagnoses of tumor staging. In this study, 20 pairs of normal and cancerous human breast tissues were imaged by multiphoton microscopy (MPM), and nuclear area and collagen density were quantified by LSM 5 software (version 3.2). Comparison of MPM images from normal breast tissue with low- and high-grade invasive ductal carcinoma (IDC) lesions clearly showed changes in both cellular features and extracellular matrix architecture during IDC development. Moreover, analysis of nuclear area and collagen density established a quantitative link between these two morphological features and progression of IDC. Present results demonstrated that MPM can provide both qualitative and quantitative evaluations of tumor progression. With additional development, this technique has the potential to make real-time histological diagnoses of tumor staging and guide development of efficacious clinical therapies.

Remodeling of the Epithelial–Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging

“…It will be of interest to explore multivariate combinations by principal component analysis or ten-fold cross validation possible with larger sample sizes. Cytologic, biochemical and microstructural abnormalities have been shown by MPAM-SHGM in neoplasia in animal models and humans (38, 44, 45). Careful investigation of these parameters collectively with cytologic and microstructural features presented here could provide a more comprehensive assessment of neoplastic alterations.…”

Two-Photon Microscopy of Stroma ex vivo for the Express Diagnostics of Breast Cancer

“…Benign changes in the breast tissue (in particular, fibroadenomatosis) are associated with excessive proliferation of the connective tissue component of stroma, which also affects the state of collagen and elastin [24]. Thus, TPM has diagnostic value in the detection of breast lesions, which is confirmed by a number of papers [15,[32][33][34][35]. High correlation of sequential changes in the organization of collagen fibers with the degree of invasion of breast tumors was observed in laboratory animals, and typical signs of remodeled collagen structure were classified as tumor-associated collagen signatures [30].…”

“…Two-photon microscopy (TPM) is one of the promising technologies for optical biopsy of biological tissue native samples [10], which was used for the analysis of tumors of various localizations [11][12][13][14][15]. The TPM approach is based on the principle of laser scanning microscopy [16], in which an infrared femtosecond pulsed laser is used as a source, and the image is formed by simultaneously registering second harmonic generation (SHG) signals from collagen and two-photon-excited autofluorescence (TPAF) from elastin and cell cytoplasm components in the visible spectral range.…”

Label-Free Identification of Early Stages of Breast Ductal Carcinoma via Multiphoton Microscopy

“…MPM, targeting SHG and TPEF, has been widely used as a very useful tool in cancer research and detection, such as intraoperative real-time detection, marginal implementation assessment, and cancer diagnosis [13,19,[21][22][23][24]. Moreover, MPM also plays an important role in breast cancer research, including rapid intraoperative evaluation of breast lesions, detection of breast tumor progression, and the role of collagen density in the mammary tumor initiation and progression [15,25,26]. However, few MPM studies have been conducted on these early stages of breast ductal carcinoma [16], especially on MPM imaging of ADH and DCIS-MI.…”