Abstract 2825: Using SHG to study breast cancer tumor progression.

Abstract

Abstract The majority of cancer mortality is a result of metastatic events, making it increasingly important to uncover prognostic markers that can predict the metastatic potential of a primary tumor to aid in determining the best course of patient treatment. Stromal extracellular matrix restructuring increases efficiency of cell migration away from the primary tumor into surrounding tissues and vasculature, thereby enhancing metastatic potential. We have determined that the ratio of the forward propagating to backward propagating Second Harmonic Generation (SHG) signals from type I collagen can be used as a quantitative method of differentiating healthy and tumor breast tissue, and tracking stromal changes throughout tumor progression. Tumors were graded and staged according to standard pathological qualifications, incorporating morphological changes in the tissue as well as extent of tumor growth and invasion. As the tumor cells initiate development in the ducts of the breast tissue the F/B ratio of the fibrillar collagen does not change. Upon progression from an in situ to an invasive carcinoma the F/B ratio of ductal tumors significantly decreases. Taking a closer look at this phenomenon, to examine whether the invasion through the basement membrane into the surrounding tissue causes an immediate change in the F/B ratio, tumors of varying grade and stage were analyzed showing significant trends throughout development. Increased tumor grade was associated with a gradual decrease in the F/B ratio, whereas size of the tumor had no significant effect on the F/B but all sizes were significantly lower than healthy tissue. Interestingly, there was a significant increase in the F/B ratio associated with the furthest progression of lymph-node involvement. Invasive Lobular Carcinoma analysis revealed a similar decrease in F/B, but was not affected by lymph node involvement. On the other hand F/B of these tumors was significantly affected by an interaction with the chest or skin. These results provide insight into the different development processes undergone by two related breast carcinomas, which could differ due to their alternative methods of invasion and stromal components. F/B ratio measurements can be used alongside pathological analysis to provide information about the metastatic potential of the primary tumor, as demonstrated by the relationship between F/B ratio of IDC and lymph node metastasis. Enhanced scientific understanding of stromal development could be applied to the development of improved biomarkers and metastatic treatment methods. Citation Format: Kathleen A. Burke, Edward Brown. Using SHG to study breast cancer tumor progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2825. doi:10.1158/1538-7445.AM2013-2825