Fuat Demirkiran

The relationship between histopathological data and molecular alterations with oncological outcomes in endometrioid-type endometrial cancers and a novel POLE mutation

To identify molecular subgroups in endometrioid endometrial cancer (EEC), evaluate their association with clinicohistopathological characteristics, and define low-intermediate risk groups by integrating these parameters. This retrospective-cohort study included 1,040 patients who underwent surgery between January 2000 and June 2022. Among 900 EEC cases, 72 recurred. Patients with tumor recurrence (n=62) and those without (n=52) were matched. POLE exons 9-14 were examined using Sanger sequencing. p53 and mismatch repair (MMR) protein expression were assessed via immunohistochemistry. The molecular subgroups were POLE mutation (POLE-mut) 5%, mismatch repair-deficient (MMR-d) 43%, p53 mutation (p53-mut) 5%, and non-specific molecular profile (NSMP) 42%. 5% of cases displayed multiple molecular mutations. POLE-mut were more prevalent in high-grade tumors (p=0.026). MMR-d tumors exhibited higher rates of lymphovascular space invasion and myometrial invasion ≥50% (p=0.032, p=0.020). No recurrences occurred in POLE-mut tumors (p=0.002), while MMR-d was significantly associated with recurrence (p=0.002). Median disease-free survival (DFS) for MMR-d, p53-mut, and NSMP were 34, 49, and 107 months, respectively. Median overall survival (OS) for these groups was 128, 102, and 181 months. Multivariate Cox-regression analysis employing the Backward-Stepwise method identified stage as the strongest predictor of DFS, and grade and stage as predictors of OS. POLE mutations were linked to the most favorable molecular prognostic factor. NSMP cases showed the longest DFS and OS, while p53-mut had the shortest OS. Except for POLE, molecular features alone were insufficient for establishing risk groups, highlighting the continued importance of histopathology in EEC management.

Could the Long-Term Oncological Safety of Laparoscopic Surgery in Low-Risk Endometrial Cancer also Be Valid for the High–Intermediate- and High-Risk Patients? A Multi-Center Turkish Gynecologic Oncology Group Study Conducted with 2745 Endometrial Cancer Cases. (TRSGO-End-001)

This study was conducted to compare the long-term oncological outcomes of laparotomy and laparoscopic surgeries in endometrial cancer under the light of the 2016 ESMO-ESGO-ESTRO risk classification system, with particular focus on the high–intermediate- and high-risk categories. Using multicentric databases between January 2005 and January 2016, disease-free and overall survivals of 2745 endometrial cancer cases were compared according to the surgery route (laparotomy vs. laparoscopy). The high–intermediate- and high-risk patients were defined with respect to the 2016 ESMO-ESGO-ESTRO risk classification system, and they were analyzed with respect to differences in survival rates. Of the 2745 patients, 1743 (63.5%) were operated by laparotomy, and the remaining were operated with laparoscopy. The total numbers of high–intermediate- and high-risk endometrial cancer cases were 734 (45%) patients in the laparotomy group and 307 (30.7%) patients in the laparoscopy group. Disease-free and overall survivals were not statistically different when compared between laparoscopy and laparotomy groups in terms of low-, intermediate-, high–intermediate- and high-risk endometrial cancer. In conclusion, regardless of the endometrial cancer risk category, long-term oncological outcomes of the laparoscopic approach were found to be comparable to those treated with laparotomy. Our results are encouraging to consider laparoscopic surgery for high–intermediate- and high-risk endometrial cancer cases.

Juvenile granulosa cell tumor: 20 years’ experience of a Tertiary Center

The aim of this study is to share of the 20-year experience of a tertiary center about juvenile granulosa cell tumor (JGCT) and describe clinic manifestations, treatment, and outcome of patients who diagnosed JGCT. Five patients who diagnosed juvenile granulosa cell tumor between 2000 and 2020 were included in the study. The demographics, clinical findings and outcomes were retrospectively evaluated. Of the 5 patients in our study, one was in the premenarcheal girl. The common complaint in all of our patients was abdominal swelling. In preoperative imaging methods, all patients had unilateral adnexal mass and no signs in favor of metastasis. All patients were staged according to FIGO classification for ovarian tumors; 3 of patients had stage IA disease, one of patients had stage IC1 and one of patients had stage IC2. All patients underwent different surgecal procedures which is appropriate for their clinical manifestations. In addition to surgery 2 patients received adjuvant chemotherapy. The median follow-up period of the patients was 60 mounts and recurrence was observed in two patients who were reoperated. We have no patients who died due to this disease. Possible diagnosis of juvenile granulosa cell tumor should be kept in mind in a patient of young age with unilateral adnexal mass with benign features.

Correspondence on: The risk of lymph node metastasis in the new FIGO 2018 stage IA cervical cancer with >7 mm diameter by Nicolai et al.

Comparison of oncologic outcome of preoveratively presumed low-risk endometrial cancer patients who underwent only bilateral pelvic sentinel lymph node (SLN) removal and those who underwent pelvic lymphadenectomy in addition to bilateral pelvic SLN removal: Turkish Gynecologic Oncology Group (TRSGO-SLN-009)

We aimed to compare the oncological outcomes of patients with bilateral sentinel lymph nodes (SLNs) detection and removed with those who underwent pelvic lymphadenectomy (PLA) in addition to bilateral SLNs removal. This multicenter, retrospective study included cases of endometrioid type, grade I-II endometrial cancer, in which bilateral SLNs were detected and removed. Patients who had only bilateral SLNs detected and removed (group I) and patients who had bilateral SLNs detected and removed and subsequent additional bilateral PLA (group II) were included in the evaluation. In group I (n=216), SLN metastasis rate was 5.5% and in group II (n=251), it was 10.3%. The low-volume disease detection rate was 4.6% in group I and 4.8% in group II. In group II, in patients with SLN macrometastasis had also 28.6% non-SLN macrometastasis. No false-negative results occurred in group II. Recurrence was detected 1.8% in group I and 5% in group II; however, there was no significant difference (p=0.083). Disease-free survival and overall survival, were almost same between the groups (hazard ratio [HR]=2.11; 95% confidence interval [CI]=0.681-6.588; p=0.187) and (HR=1.531; 95% CI=0.392-5.975; p=0.537), respectively. SLN mapping, ultrastaging, and immunohistochemical staining can identify low-volume metastases that may not be identified with classic lymphadenectomy and hematoxylin & eosin staining. It has been observed that adding PLA beyond SLN mapping did not provide an additional positive contribution to survival. For endometriod type grade I-II patients, detection of bilateral SLNs in both hemipelvis only, if detectable, is an adequate approach.