Abstract 3691: Collagen 1 fiber content may predict for recurrence in non-small cell lung cancer

Abstract

Abstract Non-small cell lung carcinoma (NSCLC) comprises 85% of all lung cancers. Approximately 30-50% of NSCLC recur despite curative resection. There is a major unmet need to identify NSCLC that are likely to recur so that these patients may be treated with more aggressive therapies. Collagen 1 (Col1) fibers are a major structural component of the extracellular matrix (ECM) of tumors. While increased Col1 fibers have been associated with increased metastasis in breast cancer, the role of Col1 in NSCLC and its relationship to recurrence has not been previously examined. We performed a blinded second harmonic generation (SHG) microscopy study on tumor tissue obtained from 5 patients with nonrecurrent NSCLC and 5 patients with recurrent NSCLC. Col1 fibers were detected with SHG microscopy that detects an intrinsic signal derived from the noncentrosymmetric molecular structure of Col1 fibers. SHG microscopy of tumor regions was performed on the H&E sections to quantify Col1 fiber volume and inter fiber distance in the tumors. At least 10 fields of view were analyzed from 1-2 sections obtained from each tumor. We additionally performed Haralick feature analyses to further analyze Col1 fiber patterns. Adjacent sections were immunostained for CD44 and α-SMA to identify cancer associated fibroblasts (CAFs) and understand their role in these tumors. We observed a significant increase of Col1 fiber volume and a significant decrease of inter fiber distance in recurrent NSCLC. Four Haralick features (orientation, contrast, energy and homogeneity) were also significantly higher in the recurrent tumors compared to the non recurrent tumors. We are currently analyzing the CAFs in the tumor sections to understand their role in the significant differences observed in Col1 fibers between recurrent and nonrecurrent tumors. If these preliminary data are confirmed in an expanded sample set, Col1 fiber analysis may provide a companion diagnostic test that can be performed rapidly on H&E tumor sections, using a confocal microscope, to evaluate the likelihood of tumor recurrence. These studies provide new insights into the role of the tumor microenvironment in NSCLC recurrence, and identify new targets for future therapeutic strategies. This work was supported in part by NIH R35CA209960. Citation Format: Samata Kakkad, Peng Huang, Malcolm Brock, Balaji Krishnamachary, Zaver M. Bhujwalla. Collagen 1 fiber content may predict for recurrence in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3691.