Detection of somatic mutations in peritoneal lavages and plasma of endometrial cancer patients: A proof‐of‐concept study

• Published in: International journal of cancer Vol. 147; no. 1; pp. 277 - 284
• Main Authors: Mayo‐de‐las‐Casas, Clara, Velasco, Ana, Sanchez, Douglas, Martínez‐Bueno, Alejandro, Garzón‐Ibáñez, Mónica, Gatius, Sònia, Ruiz‐Miró, Maria, Gonzalez‐Tallada, Xavier, Llordella, Ivana, Tresserra, Francesc, Rodríguez, Sonia, Aldeguer, Erika, Roman‐Canal, Berta, Bertran‐Alamillo, Jordi, García‐Peláez, Beatriz, Rosell, Rafael, Molina‐Vila, Miguel A., Matias‐Guiu, Xavier
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-07-2020; Wiley Subscription Services, Inc
• Subjects: Aged; Aged, 80 and over; Alleles; Biopsy; Cancer; Chemotherapy; circulating free DNA; Class I Phosphatidylinositol 3-Kinases - genetics; Cytology; DNA Mutational Analysis; DNA sequencing; DNA, Circular - blood; DNA, Circular - genetics; Endometrial cancer; Endometrial Neoplasms - blood; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; Endometrium; Female; Guanosine triphosphatases; High-Throughput Nucleotide Sequencing; Humans; Liquid Biopsy; Malignancy; Medical research; Middle Aged; Mutation; Mutation hot spots; Patients; Peritoneal Lavage - methods; peritoneal lavages; Peritoneum; Phosphatidylinositol; Polymerase chain reaction; Proof of Concept Study; Proto-Oncogene Proteins p21(ras) - genetics; Real-Time Polymerase Chain Reaction; somatic mutations; Surgery; somatic mutations; endometrial cancer; peritoneal lavages; liquid biopsy; circulating free DNA
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32872

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Although most patients are diagnosed at early stages, 15–20% will relapse despite local treatment. Presently, there are no reliable markers to identify patients with worse outcomes who may benefit from adjuvant treatments, such as chemotherapy, and liquid biopsies may be of use in this setting. Peritoneal lavages are systematically performed during endometrial surgery but little data are available about their potential as liquid biopsies. We analyzed KRAS and PIK3CA mutations in paired surgical biopsies, blood and cytology‐negative peritoneal lavages in a cohort of 50 EC patients. Surgical biopsies were submitted to next‐generation sequencing (NGS) while circulating‐free DNA (cfDNA) purified from plasma and peritoneal lavages was analyzed for KRAS and PIK3CA hotspot mutations using a sensitive quantitative polymerase chain reaction (PCR) assay. NGS of biopsies revealed KRAS, PIK3CA or concomitant KRAS + PIK3CA mutations in 33/50 (66%) EC patients. Of those, 19 cases carried hotspot mutations. Quantitative PCR revealed KRAS and/or PIK3CA mutations in the lavages of 9/19 (47.4%) hotspot EC patients. In contrast, only 2/19 (10.5%) blood samples from hotspot EC patients were positive. Mutations found in cfDNA consistently matched those in paired biopsies. One of the two patients positive in plasma and lavage died in less than 6 months. In conclusion, mutational analysis in peritoneal lavages and blood from early stage EC is feasible. Further studies are warranted to determine if it might help to identify patients with worse prognosis. Human genes discussed: KRAS, KRAS proto‐oncogene, GTPase; PIK3CA, phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha.
What's new?
To date, there are no reliable markers to identify endometrial cancer patients with worse outcomes who may benefit from adjuvant treatments. Peritoneal lavages are systematically performed during endometrial surgery, but little data is available about their potential as liquid biopsies. In this proof‐of‐concept study, the authors demonstrated that circulating‐free DNA can be purified from peritoneal lavages of surgically‐resected endometrial cancer patients. Hotspot somatic mutations were detected in a significant percentage of cases and matched tumor tissue mutations. The results warrant further studies to determine if mutation testing of liquid biopsies may help to identify endometrial cancer patients with worse prognosis.