Study: Ovarian cancer may originate in fallopian tubes
A study published in Nature Communications suggests that high-grade serous ovarian carcinoma (HGSOC) may originate in the fallopian tubes before metastasizing to the patient’s ovaries on average 6.5 years later. The authors performed whole-exome sequence and copy number analyses of laser capture microdissected fallopian tube lesions, ovarian cancers, and metastases. They found that single cell layers of cancer (p53 signatures) and serous tubal intraepithelial carcinomas (STICs) are precursors of ovarian cancer.
The researchers collected tissue samples containing normal cells, ovarian cancers, metastases that had spread elsewhere, and small cancers from the fallopian tubes. These samples came from five women who had been diagnosed with HGSOC. In addition to these samples, the researchers also collected tissue samples from STIC lesions and normal cells from four women who had undergone prophylactic removal of their ovaries and fallopian tubes due to hereditary mutations in the BRCA gene. By staining the small cancers to highlight the cells containing mistakes in the p53 gene, the researchers were able to perform whole-exome genome sequencing on all of the samples. This helped separate the normal genes from cancer-linked DNA errors and helped identify altered DNA in a particular chromosome.
All nine patients showed evidence of identical lost regions of chromosome 17, where the cancer-linked p53 gene is located. This loss is included in the early-stage STIC lesions, which the authors believe suggests that the p53 gene is an early step in ovarian cancer development. The researchers then used multiple statistical models that took the patients’ age at diagnosis into account to determine the amount of time it took for the cancers to form. Their results indicate that ovarian cancers developed from STIC lesions within an average of 6.5 years among the patients analyzed. But once the cancer had reached the ovaries, the disease metastasized rapidly, within 2 years on average. The authors noted that their findings indicate that removal of the fallopian tubes rather than the ovaries in BRCA carriers and non-carriers may be curative as it would eliminate the precursors of ovarian cancer.
The study authors recognized that there were limitations to the study. The study needs to be performed with a larger subject pool to determine whether or not the findings are replicable. In addition, the analysis was limited to ovarian cancers where STICs and other concomitant lesions were identified, which may not be representative of all HGOCs. The precise timing of when potentially malignant cells travel from the fallopian tubes into the ovary is unknown so removal of the tubes may not provide the best risk-reduction. While more research is needed, the researchers hope their findings can eventually be used to help diagnose and treat ovarian cancer much earlier.