Imaging Collagen Alterations in STICs and High Grade Ovarian Cancers in the Fallopian Tubes by Second Harmonic Generation Microscopy.

Eric C Rentchler,Manish Patankar,Ronny Drapkin,Paul J Campagnola,Kristal L Gant

doi:10.3390/cancers11111805

Eric C Rentchler, Manish Patankar + Show 3 more

Open Access

https://doi.org/10.3390/cancers11111805

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Abstract

The majority of high-grade serous ovarian cancers originate in the fallopian tubes, however, the corresponding structural changes in the extracellular matrix (ECM) have not been well-characterized. This information could provide new insight into the carcinogenesis and provide the basis for new diagnostic tools. We have previously used the collagen-specific Second Harmonic Generation (SHG) microscopy to probe collagen fiber alterations in high-grade serous ovarian cancer and in other ovarian tumors, and showed they could be uniquely identified by machine learning approaches. Here we couple SHG imaging of serous tubal intra-epithelial carcinomas (STICs), high-grade cancers, and normal regions of the fallopian tubes, using three distinct image analysis approaches to form a classification scheme based on the respective collagen fiber morphology. Using a linear discriminant analysis, we achieved near 100% classification accuracy between high-grade disease and the other tissues, where the STICs and normal regions were differentiated with ~75% accuracy. Importantly, the collagen in high-grade disease in both the fallopian tube and the ovary itself have a similar collagen morphology, further substantiating the metastasis between these sites. This analysis provides a new method of classification, but also quantifies the structural changes in the disease, which may provide new insight into metastasis.

Highlights

High grade serous ovarian cancer (HGSOC) is an often-fatal disease usually detected at an advanced stage when options for treatment are limited
~35% of patients survive for five years when diagnosed with advanced stage disease, whereas, by comparison, ~70% of patients survive for that duration when HGSOC is detected at an early stage [1]
In this work we collected two distinct Second Harmonic Generation (SHG) channels, i.e., forward and backward propagating signals. This is distinct from fluorescence, where, by widefield or confocal or multiphoton microscopy, the light emission is collected in the epi-direction

Summary

Introduction

High grade serous ovarian cancer (HGSOC) is an often-fatal disease usually detected at an advanced stage when options for treatment are limited. ~35% of patients survive for five years when diagnosed with advanced stage disease, whereas, by comparison, ~70% of patients survive for that duration when HGSOC is detected at an early stage [1] These statistics have not changed significantly for the past several decades and there remains a clear need for more sensitive diagnostic modalities. Standard clinical imaging modalities including CT, MRI, ultrasound, and PET do not have sufficient resolution and/or sensitivity for detection of early lesions [2,3,4] These shortcomings are especially important for HGSOC, as small lesions can metastasize to the omentum and other locations in the peritoneum [5,6,7]. Referred to as ovarian cancer, in a majority of patients, many high-grade serous cancers originate from the secretory

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Conclusion