Abstract 4299: Collagen 1 fiber content can predict for recurrence in stage 1 non-small cell lung cancer
Authors: Kakkad Samata , Huang Peng , Brock Malcom , Krishnamachary Balaji , Bhujwalla Zaver M. 
Published: September 2020

Abstract
Introduction: Non-small cell lung carcinoma (NSCLC) comprises 85% of all lung cancers. Since most stage 1 NSCLC can be cured by surgery alone, these patients generally do not receive further cancer treatment. However, 20-30% of them will have their lung cancer progressed and died from it. There is a major unmet need to early identify those individuals who are likely to recur so that they can benefit from current effective cancer treatments. 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.
Method: We performed a blinded second harmonic generation (SHG) microscopy study on surgically resected tumor histology tissue sections obtained from twelve patients with non-recurrent stage 1 NSCLC and fourteen patients with recurrent stage 1 NSCLC from The National Lung Screening Trial (NLST) project conducted by the National Institute of Health (NIH). 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 patient sample. We additionally performed Haralick feature analyses to further analyze Col1 fiber patterns. We also performed tile scan SHG on four patient samples (two non-recurrent and two recurrent) to acquire the Col1 fiber distribution over the entire tissue sample.
Results: We observed a significant increase of Col1 fiber volume and a significant decrease of inter fiber distance in recurrent NSCLC. Three Haralick features (contrast, energy and homogeneity) were also significantly different in the recurrent tumors compared to the non-recurrent tumors. The tile scan dataset revealed thick long fiber tracks throughout the tumor regions in the recurrent NSCLC compared to short and less dense fiber distribution in the tumor regions of the non-recurrent NSCLC.
Conclusions: Col1 fiber analysis may provide a companion diagnostic test that can be performed rapidly on H&E tumor sections, using a multiphoton 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 by NIH R35CA209960.
Citation Format: Samata Kakkad, Peng Huang, Malcom Brock, Balaji Krishnamachary, Zaver M. Bhujwalla. Collagen 1 fiber content can predict for recurrence in stage 1 non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4299.