Detection of Somatic TP53 Mutations in Tampons of Patients With High-Grade Serous Ovarian Cancer

Abstract

Objective To investigate if tumor cells could be detected in the vagina of women with serous ovarian cancer through TP53 analysis of DNA samples collected by placement of a vaginal tampon. Methods Women undergoing surgery for a pelvic mass were identified in the gynecologic oncology clinic. They placed a vaginal tampon prior to surgery, which was removed in the operating room. Cells were isolated and DNA was extracted from both the cells trapped within the tampon and the primary tumor. In patients with serous carcinoma, the DNA was interrogated for the presence of TP53 mutations using a method capable of detecting rare mutant alleles in a mixture of mutant and wild-type DNA. Results Thirty-three patients were enrolled. Eight patients with advanced serous ovarian cancer were included for analysis. Three had a prior tubal ligation. TP53 mutations were identified in all eight tumor samples. Analysis of the DNA from the tampons revealed mutations in three of the five patients with intact tubes (sensitivity 60%) and in none of the three patients with tubal ligation. In all three participants with mutation detected in the tampon specimen, the tumor and the vaginal DNA harbored the exact same TP53 mutation. The fraction of DNA derived from exfoliated tumor cells ranged from 0.01–0.07%. Conclusion In this pilot study, DNA derived from tumor was detected in the vagina of 60% of ovarian cancer patients with intact fallopian tubes. With further development, this approach may hold promise for the early detection of this deadly disease.

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Genome-wide analysis of gynecologic cancer: The Cancer Genome Atlas in ovarian and endometrial cancer

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