Abstract 6166: A whole-organ ex vivo optical imaging technique for non-destructive, more precise identification of serous tubal intraepithelial carcinoma (STIC) in fallopian tubes

Abstract

Abstract Objective With the recent discovery of the fallopian tube (FT) origin of the most common and lethal type of ovarian cancer, high grade serous cancer (HGSC), engineering solutions to overcome the limitations of standard histopathology to more reliably identify incipient HGSCs and their serous tubal intraepithelial carcinoma (STIC) precursors are much needed. This investigation tests the potential of whole-organ ex vivo optical imaging of freshly excised FTs to label and sample abnormal tubal epithelium prior to formalin fixation and paraffin embedding for standard histopathology. Methods This investigation prototyped “OVASEEK”, a whole-organ, near-infrared optical imaging platform for identification of STICs. This prospective biospecimen protocol with annotated clinical data was approved by the IRB. Following salpingectomy at the time of hysterectomy for benign indications, FTs from study participants are longitudinally bivalved. Half of the FT is retained for routine evaluation using the Sectioning and Extensively Examining the Fimbriated end (SEE-FIM) protocol by Johns Hopkins gynecologic pathologists (Gyn Path), while the other half is sent overnight in organ transplant media to MIT for imaging on OVASEEK. Hyperspectral “label free” first pass imaging is performed using a series of band-pass filters. Second pass fluorescence imaging is then performed using nanoparticles tagged with anti-LAMC1 antibodies targeting laminin γ1, a known STIC surface marker. Abnormal signal(s) on OVASEEK imaging of the FT epithelium are tattooed with black ink, the tissue is formalin fixed and returned to Gyn Path for serial sectioning. Research findings are reported in an addendum to the formal pathology report in the electronic medical record and discussed with the patient by the gynecologic oncologist co-investigator. Results OVASEEK enabled non-destructive imaging over a wide field-of-view ~ 12×12 cm, with features of interest in the 1,050-1,550 nm range. In this pilot study, OVASEEK identified histopathologic abnormalities missed by standard SEE-FIM in 20% of FTs (n=2 out of 10). In each case, OVASEEK found microscopic (~200 µm) foci of salpingitis, a lymphoplasmacytic infiltrate consistent with inflammation. Performance of serial sectioning and histopathologic examination of the tattooed epithelium yielded this diagnosis. Conclusion Work is ongoing to improve the resolution, speed and sensitivity of OVASEEK for STIC detection. Identification of µm-sized foci of inflammation using OVASEEK is proof-of-principle that whole-organ ex vivo imaging of freshly excised FTs may be an innovation that improves the diagnostic performance of routine histopathology. Accurate and reproducible diagnosis of STIC and concurrent microscopic HGSC is imperative to the understanding of the early pathogenesis of HGSC in clinically actionable ways. Citation Format: Neelkanth M. Bardhan, Vivek Rastogi, Rebecca L. Stone, Angela M. Belcher. A whole-organ ex vivo optical imaging technique for non-destructive, more precise identification of serous tubal intraepithelial carcinoma (STIC) in fallopian tubes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6166.