Correlation of prognostic factors and degree of myometrial invasion in endometrial carcinoma: prospective cohort study

The aim of this study is to assess the type and degree of correlation of prognostic factors with the degree of myometrial invasion (MI) in subjects with endometrial cancer (EC). The research included 60 female subjects hospitalized for a planned surgical procedure, due to histopathologically (PHD) proven EC in the period from 2019 to 2021. The following parameters were monitored and analyzed: histopathological parameters: histological type, MI in millimeters and percentages, distance of the tumor from the serosa, lymphovascular invasion, invasion of the stroma and mucosa of the cervix, invasion of the ovary or uterine tube, lymph node metastases, and the International Federation of Gynecology and Obstetrics (FIGO) stage. Patients were divided into two groups, after surgery and PHD assessment of MI degree, into those with less than and more than 50% MI. Statistical data processing was done in the SPSS 24.0 software package (Chicago, IL, USA). Out of the total number of patients (60), MI <50% was present in 34 (56.6%) patients, and >50% in 26 (43.4%). Our study showed that the anteroposterior (AP) diameter of the EC and the uterine wall is significantly larger with >50% myometrial invasion, while the AP diameter of the remaining myometrium is significantly smaller. A significant finding of our study is that the cut-off value of 11 mm for the distance of EC from the serosa correlates with the degree of MI. Based on the results of our study, we came to the conclusions that the degree of MI >50% correlates with the AP diameter of the EC, the distance of the tumor from the serosa, and that it is a significant predictor of the existence of lymphovascular invasion, invasion of the uterine cervix and adnexa.

Endometrial cancer; Prognostic factors; Myometrial invasion

[1] Cerovac A, Ljuca D, Arnautalic L, Habek D, Bogdanovic G, Mustedanagic-Mujanovic J, et al. Efficacy of transvaginal ultrasound versus magnetic resonance imaging for preoperative assessment of myometrial invasion in patients with endometrioid endometrial cancer: a prospective comparative study. Radiology and Oncology. 2022; 56: 37–45.

[2] Maheshwari A, Gupta S, Prat J. A proposal for updating the staging of endometrial cancer. International Journal of Gynecology & Obstetrics. 2019; 145: 245–252.

[3] Lee K, Ki K, Lee J, Lee J, Kim JW, Cho C, et al. The risk of lymph node metastasis based on myometrial invasion and tumor grade in endometrioid uterine cancers: a multicenter, retrospective korean study. Annals of Surgical Oncology. 2009; 16: 2882–2887.

[4] Laufer J, Scasso S, Papadia A, Sosa C, Cirillo F, Raspagliesi F. Association between tumor diameter and lymphovascular space invasion among women with early-stage endometrial cancer. International Journal of Gynecology & Obstetrics. 2013; 123: 142–145.

[5] Boyraz G, Salman MC, Gultekin M, Basaran D, Cagan M, Ozgul N, et al. Incidence of lymph node metastasis in surgically staged FIGO IA G1/G2 endometrial cancer with a tumor size of more than 2 cm. International Journal of Gynecological Cancer. 2017; 27: 486–492.

[6] Coll-de la Rubia E, Martinez-Garcia E, Dittmar G, Gil-Moreno A, Cabrera S, Colas E. Prognostic biomarkers in endometrial cancer: a systematic review and meta-analysis. Journal of Clinical Medicine. 2020; 17: 1900.

[7] Matsuo K, Garcia‐Sayre J, Medeiros F, Casabar JK, Machida H, Moeini A, et al. Impact of depth and extent of lymphovascular space invasion on lymph node metastasis and recurrence patterns in endometrial cancer. Journal of Surgical Oncology. 2015; 112: 669–676.

[8] Rafiee A, Mohammadizadeh F. Association of lymphovascular space invasion (LVSI) with histological tumor grade and myometrial invasion in endometrial carcinoma: a review study. Advanced Biomedical Research. 2023; 12: 159.

[9] Zaino RJ, Abendroth C, Yemelyanova A, Oliva E, Lim D, Soslow R, et al. Endocervical involvement in endometrial adenocarcinoma is not prognostically significant and the pathologic assessment of the pattern of involvement is not reproducible. Gynecologic Oncology. 2013; 128: 83–87.

[10] Ozbilen O, Sakarya DK, Bezircioglu I, Kasap B, Yetimalar H, Yigit S. Comparison of myometrial invasion and tumor free distance from uterine serosa in endometrial cancer. Asian Pacific Journal of Cancer Prevention. 2015; 16: 519–522.

[11] Harbin LM, Berry LK, Wahlquist AE, Richmond J, Graybill WS, Kohler MF, et al. Tumor proximity to serosal surface as an independent prognostic factor in FIGO stage 1 endometrial cancer. European Journal of Gynaecological Oncology. 2021; 42: 574–579.

[12] Pineda L, Alcázar JL, Caparrós M, Mínguez JA, Idoate MA, Quiceno H, et al. Agreement between preoperative transvaginal ultrasound and intraoperative macroscopic examination for assessing myometrial infiltration in low‐risk endometrioid carcinoma. Ultrasound in Obstetrics & Gynecology. 2016; 47: 369–373.

[13] Baiocchi G, Clemente AG, Mantoan H, da Costa WL, Bovolim G, Guimaraes APG, et al. Adnexal involvement in endometrial cancer: prognostic factors and implications for ovarian preservation. Annals of Surgical Oncology. 2020; 27: 2822–2826.

[14] Li J, Zhu Q, Yang B, Ning C, Liu X, Luo X, et al. Risk factors for ovarian involvement in young and premenopausal endometrioid endometrial cancer patients. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2018; 222: 151–154.

[15] Lin KY, Miller DS, Bailey AA, Andrews SJ, Kehoe SM, Richardson DL, et al. Ovarian involvement in endometrioid adenocarcinoma of uterus. Gynecologic Oncology. 2015; 138: 532–535.

[16] Salman L, Cusimano MC, Marchocki Z, Ferguson SE. Sentinel lymph node mapping in endometrial cancer: current evidence and practice. Journal of Surgical Oncology. 2024; 129: 117–119.

[17] Wenxin Zheng. Molecular classification of endometrial cancer and the 2023 FIGO staging: exploring the challenges and opportunities for pathologists. Cancers. 2023; 15: 4101.

[18] Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. International Journal of Gynecologic Cancer. 2021; 31: 12–39.

[19] Kim SI, Yoon JH, Lee SJ, Song MJ, Kim JH, Lee HN, et al. Prediction of lymphovascular space invasion in patients with endometrial cancer. International Journal of Medical Sciences. 2021; 18: 2828–2834.

[20] Kondalsamy-Chennakesavan S, Vugt SV, Sanday K, Nicklin J, Land R, Perrin L, et al. Evaluation of tumor-free distance and depth of myometrial invasion as prognostic factors for lymph node metastases in endometrial cancer. International Journal of Gynecological Cancer. 2010; 20: 1217–1221.

[21] Oge T, Comert DK, Cakmak Y, Arık D. Is tumor-free distance an independent prognostic factor for early-stage endometrioid endometrial cancer? Journal of Oncology. 2020; 2020: 2934291.

[22] Kalogera E, Scholler N, Powless C, Weaver A, Drapkin R, Li J, et al. Correlation of serum he4 with tumor size and myometrial invasion in endometrial cancer. Gynecologic Oncology. 2012; 124: 270–275.

[23] Oliver-Perez MR, Magriña J, Villalain-Gonzalez C, Jimenez-Lopez JS, Lopez-Gonzalez G, Barcena C, et al. Lymphovascular space invasion in endometrial carcinoma: tumor size and location matter. Surgical Oncology. 2021; 37: 101541.

[24] O’Toole SA, Huang Y, Norris L, Power Foley M, Shireen R, McDonald S, et al. He4 and CA125 as preoperative risk stratifiers for lymph node metastasis in endometrioid carcinoma of the endometrium: a retrospective study in a cohort with histological proof of lymph node status. Gynecologic Oncology. 2021; 160: 514–519.

[25] Espiau Romera A, Coronado Martín PJ, Chóliz Ezquerro M, Cuesta Guardiola T, Adiego Calvo I, Baquedano Mainar L. Value of preoperative HE4 as predictor of advanced disease in endometrioid endometrial cancer. International Journal of Gynecology & Obstetrics. 2021; 153: 64–70.

[26] Prueksaritanond N, Cheanpracha P, Yanaranop M. Association of serum HE4 with primary tumor diameter and depth of myometrial invasion in endometrial cancer patients at Rajavithi hospital. Asian Pacific Journal of Cancer Prevention. 2016; 17: 1489–1492.

[27] van der Putten LJM, van de Vijver K, Bartosch C, Davidson B, Gatius S, Matias-Guiu X, et al. Reproducibility of measurement of myometrial invasion in endometrial carcinoma. Virchows Archiv. 2017; 470: 63–68.

[28] Stiekema A, Lok C, Korse C, van Driel W, van der Noort V, Kenter G, et al. Serum HE4 is correlated to prognostic factors and survival in patients with endometrial cancer. Virchows Archiv. 2017; 470: 655–664.

[29] Chattopadhyay S, Galaal K, Patel A, Fisher A, Nayar A, Cross P, et al. Tumour‐free distance from serosa is a better prognostic indicator than depth of invasion and percentage myometrial invasion in endometrioid endometrial cancer. BJOG: An International Journal of Obstetrics & Gynaecology. 2012; 119: 1162–1170.

[30] Doghri R, Chaabouni S, Houcine Y, Charfi L, Boujelbene N, Driss M, et al. Evaluation of tumor‑free distance and depth of myometrial invasion as prognostic factors in endometrial cancer. Molecular and Clinical Oncology. 2018; 9: 87–91.

[31] Cerovac A, Habek D, Hrgović Z. Ultrasound characteristics of myometrial invasion in endometrial carcinoma: a prospective cohort study. To be published in Clinical and Experimental Obstetrics and Gynecology. 2024. [Preprint].

[32] Berek JS, Matias-Guiu X, Creutzberg C, Fotopoulou C, Gaffney D, Kehoe S, et al. FIGO staging of endometrial cancer: 2023. International Journal of Gynaecology and Obstetrics. 2023; 162: 383–394.

[33] Schwameis R, Fanfani F, Ebner C, Zimmermann N, Peters I, Nero C, et al. Verification of the prognostic precision of the new 2023 FIGO staging system in endometrial cancer patients—an international pooled analysis of three ESGO accredited centres. European Journal of Cancer. 2023; 193: 113317.