Journal Article

Collagen organization of renal cell carcinoma differs between low and high grade tumors

Thimm, Terra N., Abel, E. Jason, Best, Sara L., Eliceiri, Kevin W., Woo, Kaitlin M., Houlihan, Matthew, Keikhosravi, Adib, Drifka, Cole R., Mehta, Guneet S., Liu, Yuming, Altwegg, Marie, Huang, Wei, Bredfeldt, Jeremy S.

2019

Overview

Background The traditional pathologic grading for human renal cell carcinoma (RCC) has low concordance between biopsy and surgical specimen. There is a need to investigate adjunctive pathology technique that does not rely on the nuclear morphology that defines the traditional grading. Changes in collagen organization in the extracellular matrix have been linked to prognosis or grade in breast, ovarian, and pancreatic cancers, but collagen organization has never been correlated with RCC grade. In this study, we used Second Harmonic Generation (SHG) based imaging to quantify possible differences in collagen organization between high and low grades of human RCC. Methods A tissue microarray (TMA) was constructed from RCC tumor specimens. Each TMA core represents an individual patient. A 5 μm section from the TMA tissue was stained with standard hematoxylin and eosin (H&E). Bright field images of the H&E stained TMA were used to annotate representative RCC regions. In this study, 70 grade 1 cores and 51 grade 4 cores were imaged on a custom-built forward SHG microscope, and images were analyzed using established software tools to automatically extract and quantify collagen fibers for alignment and density assessment. A linear mixed-effects model with random intercepts to account for the within-patient correlation was created to compare grade 1 vs. grade 4 measurements and the statistical tests were two-sided. Results Both collagen density and alignment differed significantly between RCC grade 1 and RCC grade 4. Specifically, collagen fiber density was greater in grade 4 than in grade 1 RCC ( p  < 0.001). Collagen fibers were also more aligned in grade 4 compared to grade 1 ( p  < 0.001). Conclusions Collagen density and alignment were shown to be significantly higher in RCC grade 4 vs. grade 1. This technique of biopsy sampling by SHG could complement classical tumor grading approaches. Furthermore it might allow biopsies to be more clinically relevant by informing diagnostics. Future studies are required to investigate the functional role of collagen organization in RCC.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Automation / Biomarkers, Tumor - metabolism / Biomedical and Life Sciences / Biomedicine / Biopsy / Breast cancer / Cancer / cancer imaging / Cancer Research / Carcinoma / Carcinoma, Renal Cell - diagnostic imaging / Collagen / Collagen - metabolism / Collagen organization / Extracellular matrix / Extracellular Matrix - pathology / Fibers / Functional morphology / Future predictions / Health Promotion and Disease Prevention / Humans / interventional therapeutics / Kidney - pathology / Kidney cancer / Kidney Neoplasms - diagnostic imaging / Linear Models / Medical imaging / Medical research / Medicine/Public Health / Metastasis / Microscopy / Neoplasm Grading / Oncology / Organizations / Pancreas / Pancreatic cancer / Pathology / Patients / Prevalence studies (Epidemiology) / Prognosis / Renal cell carcinoma / Research Article / Second harmonic generation imaging / Second Harmonic Generation Microscopy / Statistical analysis / Surgery / Surgical Oncology / Tissue Array Analysis / Tissue microarray / Tumor grading / Tumors