2014 Update on ovarian cancer

Thirty-three women with pelvic masses suspicious for malignancy and scheduled to undergo diagnostic or therapeutic surgery were enrolled. Of the 25 patients who placed the tampon 8 to 12 hours prior to surgery; 13 had benign disease; three had nonovarian malignancies; and nine had serous adenocarcinoma of ovarian, tubal, or primary peritoneal origin. DNA from tumor specimens of eight patients with serous carcinoma and adequate DNA samples were analyzed for TP53 mutations. The corresponding DNA extracted from the tampon was then probed for the mutation identified in the tumor.

Mutational analysis of the tampon specimen DNA revealed no mutations in the tampon DNA of the three patients who had previously undergone tubal ligation, while mutations were observed in three of the five patients with intact tubes—producing a sensitivity of 60%. The fraction of mutant alleles in the tampon DNA was extremely low at 0.01% to 0.07%, requiring ultra-deep sequencing and increasing the importance of paired primary tumor specimens.

What this evidence means for practiceWhile sensitivity in a population of high-risk patients with intact tubes was found to be 60%, it is unclear what it would be in patients with less advanced disease. The ability of the test to detect mutations at exceptionally low limits is impressive; however, it increases the risk that a variant represents a sequencing error or a sample-to-sample contamination. This study is novel in its approach to diagnosis of ovarian cancer and is a stride toward screening, providing an opportunity to further validate the technology prior to widespread use and clinical application.

Circulating tumor cells—the future of cancer management?

Obermayr E, Castillo-Tong DC, Pils D, et al. Molecular characterization of circulating tumor cells in patients with ovarian cancer improves their prognostic significance: a study of the OVCAD consortium. Gynecol Oncol. 2013;128(1):15−21.

Similar in concept to noninvasive prenatal testing for fetal aneuploidy, high circulating tumor cell (CTC) numbers have been correlated with aggressive disease, increased metastasis, and decreased time to relapse. As with cancer cells in vaginal secretions, CTCs also may provide an opportunity for early detection and targeted treatment.⁶

While many CTC studies have used epithelial cell adhesion molecule (EpCAM)−based CTC detection, results have been found to be highly variable between tumor subtypes and phase of disease.⁷ Therefore, Obermayer and colleagues sought to identify novel markers for CTCs in patients with epithelial ovarian cancer and elucidate their impact on outcome.

Details of the studyMatched ovarian cancer tissues and peripheral blood leukocytes of 35 patients underwent microarray analysis to identify novel CTC markers. Gene expression of the novel markers as well as EpCAM were analyzed using blood samples taken from 39 healthy females and from 216 patients with ovarian cancer before primary treatment and 6 months after adjuvant chemotherapy. Overexpression of at least one gene, compared with the healthy control group, was considered CTC positivity.

CTCs were detected in 24.5% of the baseline and 20.4% of the follow-up samples, of which two-thirds showed overexpression of the cyclophilin C gene (PPIC), and just a few by EpCAM overexpression. PPIC-positive CTCs during follow-up were detected significantly more often in the platinum resistant group, and indicated poor outcome even when controlling for classical prognostic parameters.

What this evidence means for practiceThe study authors found that molecular characterization of CTC is superior to CTC enumeration. Ultimately, CTC diagnostics may lead to earlier detection and more personalized treatment of ovarian cancer.

Therefore, this technology could have great impact on screening for and the survival of a large subset of patients with ovarian cancer. In addition, the cells obtained preoperatively could help assess the risk of malignancy in an ovarian mass prior to surgery, or even help in treatment planning, as we enter an era in which we have the ability to assess cancers for prognosis and features of treatment response.

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