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Review
. 2024 Apr 19;16(8):1560.
doi: 10.3390/cancers16081560.

A Perspective Review: Analyzing Collagen Alterations in Ovarian Cancer by High-Resolution Optical Microscopy

Kristal L Gant  1   2 , Manish S Patankar  1   3 , Paul J Campagnola  2   3
Affiliations
Review

A Perspective Review: Analyzing Collagen Alterations in Ovarian Cancer by High-Resolution Optical Microscopy

Kristal L Gant et al. Cancers (Basel). .

Abstract

High-grade serous ovarian cancer (HGSOC) is the predominant subtype of ovarian cancer (OC), occurring in more than 80% of patients diagnosed with this malignancy. Histological and genetic analysis have confirmed the secretory epithelial of the fallopian tube (FT) as a major site of origin of HGSOC. Although there have been significant strides in our understanding of this disease, early stage detection and diagnosis are still rare. Current clinical imaging modalities lack the ability to detect early stage pathogenesis in the fallopian tubes and the ovaries. However, there are several microscopic imaging techniques used to analyze the structural modifications in the extracellular matrix (ECM) protein collagen in ex vivo FT and ovarian tissues that potentially can be modified to fit the clinical setting. In this perspective, we evaluate and compare the myriad of optical tools available to visualize these alterations and the invaluable insights these data provide on HGSOC initiation. We also discuss the clinical implications of these findings and how these data may help novel tools for early diagnosis of HGSOC.

Keywords: ECM alterations; clinical interventions; collagen reorganization; high-grade serous ovarian cancer.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
High-grade serous ovarian cancer (HGSOC) is a difficult disease to diagnose and treat. (A) Surgical staging of ovarian cancer correlates with the prognosis of patients to conventional debulking surgery combined with platinum and taxol-based chemotherapy. (B) Most women with HGSOC experience relatively common symptoms, which, by themselves, are insufficient for cancer diagnosis. (C) Serum levels of CA125, a repeating peptide epitope of the large molecular weight mucin, MUC16, are elevated in most patients with HGSOC. Elevation of CA125 is also observed in other cancers, as well as benign conditions. Therefore, while the FDA-approved serum CA125 test is useful in monitoring the recurrence of HGSOC in women already diagnosed with this cancer, this test is not used as a screening tool for early detection of ovarian cancer.
Figure 2
Figure 2
Evaluation of the extracellular matrix surrounding ovarian tumors is providing new insights into the biology of cancer and new technologies to understand the importance of altered collagen architecture in HGSOC progression. SHG imaging of ovarian tumors has demonstrated major alterations in the collagen architecture. Our recent studies have shown that these changes in collagen occur early and can even be detected in the precursor lesion (serous tubal intraepithelial carcinoma, STIC) of HGSOC. These changes can serve as biomarkers for the disease. Our group has now developed a 3D printing approach to make mimics of the collagen based on normal and HGSOC tissues. These 3D patterns have allowed us to demonstrate that cancer-associated collagen promotes the migration of ovarian cancer cells. Finally, the demonstration that collagen is altered early in the progression of HGSOC suggests that SHG-based endoscopic or other optical methods can be developed for in vivo or ex vivo monitoring of tissues for the detection of HGSOC signatures.
Figure 3
Figure 3
(Top row): Representative single SHG optical sections of a spectrum of ovarian tissues obtained from the ovarian cortex. (Bottom row): Representative single SHG optical sections of a spectrum of HGSOC tissues from the fallopian tube precursors. Field size = 170 × 170 microns for all images. The clinical status of all samples used in this study was examined by pathologists who are trained in gynecologic pathology and who used clinically approved practices (hematoxylin staining and immunohistochemistry) to identify the tissues.
Figure 4
Figure 4
Ovarian stromal images and corresponding fabricated scaffolds. (A) SHG optical sections of collagen from the four categories of ovarian tissues. (B) Two-photon excited fluorescence images of the resulting respective tissue-engineered scaffolds. Each pattern is 200 × 200 µm in size with 10 µm in height. Scale bar = 50 µm. Reproduced by permission from ref. [51].
Figure 5
Figure 5
Summary of research perspective. This perspective expanded upon the significance of ECM modifications in ovarian cancer and the optical tools that have been utilized to visualize these alterations. However, there are other considerations to improve diagnostics and survival statistics. Figure created with biorender.com.
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Grants and funding

This work was funded under R01CA232517 and R01CA206561. KLG was supported under a diversity supplement from R01CA206561.

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