Ultramutated tumors including POLE E mutations have been described in a variety of tumors including brain, stomach, pancreas and breast carcinoma. In the genital tract, they were also found in endometrioid carcinoma and carcinosarcoma of the endometrium and more rarely in endometrioid ovarian carcinoma (9). To the best of our knowledge, we described here the first case of borderline serous peritoneal tumor with POLE E mutation and ultramutated profile. Indeed, classically, in serous borderline tumors of the ovary only hotspot mutations including mainly KRAS, BRAF, NRAS, HER2 have been identified (6).
POLE E “proofreading” domain mutation is considered as an early event in sporadic tumors with secondary accumulations of others mutations including TP53 mutations which are in theory classically observed in high grade ovarian or peritoneal serous tumors. Some of these mutations are considered only as “passenger”, unable to become fixed in the genome and to lead to biological changes. In addition, tumors with a high mutational tumoral burden including POLE E mutation are considered to have a better prognosis due in part to an effective anti-tumoral immune response (9). Interestingly, peritoneal serous borderline tumors have notably a favorable prognosis but recurrences can occur particularly if a progression to serous carcinoma is observed (4). The treatment of this tumor included hysterectomy and bilateral salpingo-oophorectomy with removal of any pelvic/omental tumor (2, 3, 10). To date no recurrence were observed in our patient.
Peritoneal serous borderline tumors have lower response rates to conventional therapy. Although, as encountered here, the mutations BRAF gene, lead to constitutive BRAF kinase phosphorylation of MEK and ERK kinases and sustained MAPK pathway signaling. Therefore, targeted therapy with BRAF inhibitors can be an effective alternative treatment for these patients (11, 12, 13).
In summary, we described the first case of perironeal serous borderline tumor with POLE E mutation and ultramutated profile. Classically, gynaecological tumors with this particular genetic profile have a more favourable prognosis but naturally, these preliminary data awaist confirmation.