Nomogram using human epididymis protein 4 predicted concurrent endometrial cancer from endometrial atypical hyperplasia before surgery.

Objective: To establish a nomogram based on presurgical predictors of concurrent endometrial cancer (EC) for patients diagnosed with endometrial atypical hyperplasia before definitive surgery (preoperative-EAH) to improve the risk stratification and clinical application. Methods: Preoperative-EAH patients who underwent hysterectomy in a tertiary hospital from January 2020 to December 2022 were retrospectively analyzed. Independent predictors from the multivariate logistic regression model were used to establish a nomogram, and bootstrap resampling was used for internal validation. Results: Of 370 preoperative-EAH patients, 23.4% were diagnosed with EC after definitive surgery (final-EC). Multivariate analyses found three independent predictors of final EC: human epididymis protein 4 (HE4) ≥43.50 pmol/L [odds ratio (OR) = 3.70; 95% confidence intervals (CI) = 2.06-6.67], body mass index (BMI) ≥ 28 kg/m2 (OR = 2.05; 95% CI = 1.14-3.69), and postmenopausal status, particularly at postmenopausal time ≥5 years (OR = 5.84, 95% CI = 2.51-13.55), which were used to establish a nomogram model. The bootstrap-corrected C-index of the nomogram was 0.733 (95% CI = 0.68-0.79), which was significantly higher than that of each individual factor. The calibration curve and decision curve showed good consistency and clinical net benefit of the model. At the maximum Youden index, 49.4% (43/87) of women in the high-risk group defined by nomogram had concurrent EC, versus 16.6% in the low-risk group (P< 0.001). Conclusion: The nomogram based on HE4, menopausal status, and BMI was found with an improved predictive value to stratify preoperative-EAH patients at high risk of concurrent EC for better clinical management.

Clinicopathological characteristics and fertility preserving treatment of atypical polypoid adenomyoma.

Objective: Atypical polypoid adenomyoma (APA) is a rare benign tumor frequently diagnosed in young women that may coexist with or progress to atypical endometrial hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). This study aimed to investigate which subset of patients with APA are prone to concurrent or subsequent EAH or EEC, evaluate the necessity of progestin treatment in patients with APA only after achieving a complete response (CR) through hysteroscopic lesion resection, and assess the impact of concurrent APA on the fertility-preserving treatment of EAH or EEC. Methods: This retrospective single-center study analyzed 86 patients with APA treated at the Obstetrics and Gynecology Hospital of Fudan University between January 2010 and October 2021. Patients with EAH or EEC only who underwent fertility-preserving treatment during the same period were matched in a 2:1 ratio with patients with concurrent APA and EAH or EEC. The clinicopathological characteristics, treatments, and prognosis were analyzed. Results: The median patient age was 31 years (range 21-47 years). Among the 86 included patients, nine underwent total hysterectomy, 62 received conservative treatment, and the remaining 15 were lost to follow-up. A comparison of the 16 patients with APA only versus the 58 patients with APA and concurrent or subsequent EAH or EEC revealed that a homeostasis model assessment of insulin resistance (HOMA-IR) of > 2.2 (P = 0.047) and high-density lipoprotein (HDL) concentration of < 1.2 mmol/L (P = 0.028) were independent risk factors for EAH or EEC in patients with APA. Among the 17 patients with APA only who received conservative treatment and achieved a CR after hysteroscopic lesion resection, 13 received hormone treatment for a median duration of 6.3 months. The median follow-up time for these 17 patients was 49.0 months, during which no recurrence of APA was observed, but six patients developed endometrial hyperplastic diseases. Regarding the impact of concurrent APA on fertility-preserving treatment for EAH or EEC, the median time to achieve a CR was 24.0 weeks (95% confidence interval [CI]: 23.0-40.4) in the APA group and 26.0 weeks (95% CI: 24.3-32.3) in the non-APA group (P = 0.424). There were no significant differences between the two groups in the outcomes of fertility-preserving treatment. Conclusion: Patients with APA only may still develop endometrial hyperplastic diseases after complete resection of the lesion under hysteroscopy to achieve a CR, particularly those with a HOMA-IR of > 2.2 or HDL concentration of < 1.2 mmol/L. Concurrent APA did not affect the efficacy of fertility-preserving treatment in patients with EAH or EEC.

PTEN mutation predicts unfavorable fertility preserving treatment outcome in the young patients with endometrioid endometrial cancer and atypical hyperplasia.

OBJECTIVE: This study aimed to investigate the impact of molecular classification and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment in the patients with endometrioid endometrial cancer (EEC) and endometrial atypical hyperplasia (EAH). METHODS: This is a single-center retrospective study. A total of 135 patients with EEC and EAH receiving fertility-preserving treatment and molecular classification were reviewed. The distribution of the four types of molecular classification was described. The impact of non-specific molecular profile (NSMP), mismatch repair-deficiency (MMRd), and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment was analyzed. RESULTS: Of the patients analyzed, 86.7% (117/136) were classified as having NSMP; 14 (10.4%), MMRd; 1 (0.7%), POLEmut EAH; and 3 (2.2%), p53abn EEC. The patients having NSMP and MMRd achieved similar 16-, 32-, and 48-week complete response rates. The patients harboring tier I and tier II PTEN mutations (PTENmut-Clin) achieved lower cumulative 32-week CR rates than those with PTEN-others (without PTENmut-Clin) (22/47, 46.8% vs. 50/74, 67.6%; p=0.023; odds ratio=0.422; 95% confidence interval [CI]=0.199-0.896). Insulin-resistance (hazard ratio [HR]=0.435; 95% CI=0.269-0.702; p=0.001) and PTENmut-Clin (HR=0.535; 95% CI=0.324-0.885; p=0.015) were independent negative predictors for lower 32-week CR rates. CONCLUSION: PTENmut-Clin is an independent risk factor for unfavorable fertility-preserving treatment outcomes in the patients with EEC and EAH. The patients with MMRd receiving fertility-preserving treatment achieved outcomes similar to those of the patients with NSMP. The molecular profiles might guide fertility-preserving treatment in the prognosis and clinical decisions.

Menopausal Status Combined with Serum CA125 Level Significantly Predicted Concurrent Endometrial Cancer in Women Diagnosed with Atypical Endometrial Hyperplasia before Surgery †.

About 10-66% of patients with atypical endometrial hyperplasia diagnosed before surgery (preoperative-AEH) are found to have concurrent endometrial cancer (EC) at definitive hysterectomy, leading to incomplete primary surgery and delayed adjuvant treatment. This study aims to investigate the potential risk factors of concurrent EC in preoperative-AEH patients in a clinical setting with a gynecological pathology review. All patients diagnosed with AEH by endometrial biopsy or curettage that then underwent definitive hysterectomy from January 2016 to December 2019 in a tertiary hospital were retrospectively analyzed. All diagnoses were reviewed by gynecological pathologists. A total of 624 preoperative-AEH patients were included, 30.4% of whom had concurrent EC. In multivariate analysis, postmenopausal status and CA125 ≥ 35 U/mL significantly correlated with concurrent EC (OR = 3.57; 95% CI = 1.80-7.06; OR = 2.15; 95% CI = 1.15-4.03). This risk was remarkably increased in patients with both postmenopausal status and CA125 ≥ 35 U/mL (OR = 16.20; 95% CI = 1.73-151.44). Notably, concurrent EC seemed to occur more frequently in women with postmenopausal time ≥ 5 years (OR = 4.04, 95% CI = 1.80-5.85). In addition, CA125 ≥ 35 U/mL seemed to be an independent risk factor (OR = 5.74; 95% CI = 1.80-18.27) for concurrent intermediate-high-risk EC. Intermediate-high-risk EC was also more commonly seen in preoperative-AEH women with postmenopausal time ≥ 5 years (OR = 5.52, 95% CI = 1.21-25.19, p = 0.027). In conclusion, preoperative-AEH patients with postmenopausal status or elevated level of CA125 might have a high risk of concurrent EC. Adequate pre-surgical evaluation might be suggested for such patients.