Insights into the field carcinogenesis of ovarian cancer based on the nanocytology of endocervical and endometrial epithelial cells

Authors


  • Significance: This work has threefold significance for ovarian cancer: Biologically, we detect nano-architectural alterations in the histologically “normal”-appearing cells of the endometrium and endocervix for ovarian field carcinogenesis. We validate the novel observation of cervical origin using miRNA expression-levels. Clinically, these results have the potential to translate into a minimally invasive early detection technique. Technologically, we demonstrate that PWS nanocytology is exquisitely sensitive to cell nano-architecture at length scales < 300nm, a paradigm shift in biomedical optics.Drs. Roy, Subramanian, and Backman are co-founders and/or shareholders in Nanocytomics LLC. All aspects of this study including data analysis and manuscript preparation were done under the supervision of the conflict of interest committee at Northwestern University.

Correspondence to: Vadim Backman, Biomedical Engineering Department, Northwestern University, Evanston, IL 60208E-mail: v-backman@northwestern.edu

Abstract

Ovarian cancer ranks fifth in cancer fatalities among American women. Although curable at early stages with surgery, most women are diagnosed with symptoms of late-stage metastatic disease. Moreover, none of the current diagnostic techniques are clinically recommended for at-risk women as they preferentially target low-grade tumors (which do not affect longevity) and fail to capture early signatures of more lethal serous tumors which originate in the fimbrae region of the fallopian tubes. Hence, the early detection of ovarian cancer is challenging given the current strategy. Recently, our group has developed a novel optical imaging technique, partial wave spectroscopic (PWS) microscopy, that can quantify the nanoscale macromolecular density fluctuations within biological cells via a biomarker, disorder strength (Ld). Using the concept of field carcinogenesis, we propose a method of detecting ovarian cancer by PWS assessment of endometrial and endocervical columnar cells. The study includes 26 patients (controls = 15, cancer = 11) for endometrium and 23 (controls = 13, cancer = 10) for endocervix. Our results highlight a significant increase in Ld (% fold-increase > 50%, p-value < 0.05) for columnar epithelial cells obtained from cancer patients compared to controls for both endocervix and endometrium. Overall, the quantification of field carcinogenic events in the endometrium and the novel observation of its extension to the cervix are unique findings in the understanding of ovarian field carcinogenesis. We further show independent validation of the presence of cervical field carcinogenesis with micro-RNA expression data.

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