Multiphoton Microscopy for Identifying Collagen Signatures Associated with Biochemical Recurrence in Prostate Cancer Patients.

Ina P Pavlova,Sujit S Nair,Ashutosh K Tewari,Natasha Kyprianou,Gustavo E Ayala,Patrick-Julien Treacy,Reza Roshandel,Parita Ratnani,Rachel Brody,Dara Lundon,Stanislaw Sobotka,Jonathan I Epstein

doi:10.3390/jpm11111061

Abstract

Prostate cancer is a heterogeneous disease that remains dormant for long periods or acts aggressively with poor clinical outcomes. Identifying aggressive prostate tumor behavior using current glandular-focused histopathological criteria is challenging. Recent evidence has implicated the stroma in modulating prostate tumor behavior and in predicting post-surgical outcomes. However, the emergence of stromal signatures has been limited, due in part to the lack of adoption of imaging modalities for stromal-specific profiling. Herein, label-free multiphoton microscopy (MPM), with its ability to image tissue with stromal-specific contrast, is used to identify prostate stromal features associated with aggressive tumor behavior and clinical outcome. MPM was performed on unstained prostatectomy specimens from 59 patients and on biopsy specimens from 17 patients with known post-surgery recurrence status. MPM-identified collagen content, organization, and morphological tumor signatures were extracted for each patient and screened for association with recurrent disease. Compared to tumors from patients whose disease did not recur, tumors from patients with recurrent disease exhibited higher MPM-identified collagen amount and collagen fiber intensity signal and width. Our study shows an association between MPM-identified stromal collagen features of prostate tumors and post-surgical disease recurrence, suggesting their potential for prostate cancer risk assessment.

Highlights

Prostate cancer (PCa) is the second most diagnosed cancer and the third leading cause of cancer death in men annually [1]
Compared with normal prostate stroma, reactive stroma has multiphoton microscopy (MPM)-detectable characteristics; its vivid red appearance is associated with regions of extracellular-rich reactive stroma due to the increase in collagen fibers, whereas the light green is associated with regions of normal stroma due to the predominance of smooth muscle cells
The present study examined the role of label-free microscopy profiling of the prostate tumor stroma to identify features associated with aggressive tumors and poor post-surgical outcomes

Summary

Introduction

Prostate cancer (PCa) is the second most diagnosed cancer and the third leading cause of cancer death in men annually [1]. There is increasing support for including stromal characteristics in clinicopathological models, PCa nodules are currently detected by relatively low-resolution visualization approaches, such as multiparametric magnetic resonance imaging, followed by a biopsy, and by examination of the hematoxylin and eosin (H&E)-stained tissue. This approach does not facilitate routine detection and quantification of subtle changes in stromal morphology and limits the identification of new features that hold promise for differentiating between aggressive and indolent cancer behavior. There is an unmet clinical need to identify such features using imaging modalities that capture both prostate stromal and glandular changes, offer subcellular resolution, ECM-specific contrast, and integrate them into existing clinical imaging protocols

Objectives

Methods

Results

Conclusion