The relationship of MELF (microcystic, elongated and fragmented) invasion pattern with prognostic factors in endometrial endometrioid adenocarcinoma

Öz

Introduction: The aim of the present study was to investigate whether the Microcystic, Elongated And Fragmented (MELF) pattern of myometrial invasion is related to an increased occurrence of lymph node metastasis and could be considered as an additional risk factor for advanced stage disease. Methods: One hundred and five patients who were operated for endometrial cancer between March 2015 and October 2020 in the Department of Obstetrics and Gynecology, Health Sciences University Bağcılar Training and Research Hospital, were included in this study. Survival and recurrence rates were evaluated between MELF positive and negative groups. Results: Disease-free survival (DFS) curves were compared between the MELF(+) and MELF(-) groups. No statistically significant difference was found between groups in terms of disease-free survival. (P=0.310). The 5-year DFS was 88.1% in the MELF(+) group, while the 5-year DFS was 93.2% in the MELF(-) group. There was no significant difference between the overall survival (OS) curves (P=0.894). While the 5-year OS was 90.8% in the MELF(+) group, the 5-year OS was 93.1% in the MELF(-) group. Conclusion: No significant effect of MELF invasion pattern was observed on disease-free survival and overall survival in endometrioid type endometrial cancer. We found a significantly higher incidence of lymphovascular space invasion (LVSI) in the MELF positive group. The presence of MELF pattern may indirectly affect the prognosis negatively with the increase in LVSI.

Anahtar Kelimeler

• Endometrial carcinoma
• MELF
• lenfovascular invasion

Endometrial endometrioid adenokarsinomda mikrokistik, elonge ve fragmente (MELF) i̇nvazyon paterninin prognostik faktörlerle i̇lişkisi

Öz

Amaç: Mikrokistik, Elonge ve Fragmente(MELF) myoinvazyon paterninin diğer histopatolojik faktörlerle ilişkili olup olmadığını ve böylece lenf nodu metastazının artmış bir görülme sıklığı ile ilişkili olup olmadığını araştırmaktı, dolayısıyla ileri evre hastalık için ek bir risk faktörü olarak değerlendirilebilir mi? Yöntem: Mart 2015 ile Ekim 2020 tarihleri arasında Sağlık Bilimleri Üniversitesi Bağcılar Eğitim ve Araştırma Hastanesi Kadın Hastalıkları ve Doğum Kliniği’nde endometrial kanser için ameliyat edilen 105 hasta bu çalışmaya dahil edildi. MELF pozitif ve negatif gruplar arasında sağkalım ve nüks oranları değerlendirildi. Bulgular: Hastalıksız sağkalım eğrileri MELF(+) ve MELF(-) gruplar arasında karşılaştırıldı. Gruplar arasında hastalıksız sağkalım açısından istatistiksel olarak anlamlı bir fark bulunamadı (P=0,310). 5 yıllık hastalıksız sağkalım MELF(+) grubunda %88,1 iken, MELF(-) grubunda %93,2 idi. Genel sağkalım eğrileri arasında anlamlı bir fark bulunmadı (P=0,894). 5 yıllık genel sağkalım MELF(+) grubunda %90,8 iken, MELF(-) grubunda %93,1 idi. Sonuç: Endometrioid tip endometrial kanserde MELF invazyon paterninin hastalıksız sağkalım ve genel sağkalım üzerinde anlamlı bir etkisi gözlenmedi. MELF pozitif grupta anlamlı derecede daha yüksek bir LVSI insidansı bulduk. MELF paterninin varlığı, LVSI’da artışla dolaylı olarak prognozu olumsuz etkileyebilir.

Anahtar Kelimeler

• Endometrium karsinomu
• MELF
• lenfovasküler invazyon

Kaynakça

1. Morice P, Leary A, Creutzberg C, Abu-Rustum N, Darai E. Endometrial cancer. Lancet. 2016 Mar 12;387(10023):1094-1108. doi: 10.1016/S0140-6736(15)00130-0. Epub 2015 Sep 6. PMID: 26354523.
2. Cole AJ, Quick CM. Patterns of myoinvasion in endometrial adenocarcinoma: recognition and implications. Adv Anat Pathol. 2013 May;20(3):141-7. doi: 10.1097/PAP.0b013e31828d17cc. PMID: 23574770.
3. Quick CM, May T, Horowitz NS, Nucci MR. Low-grade, low-stage endometrioid endometrial adenocarcinoma: a clini-copathologic analysis of 324 cases focusing on frequency and pattern of myoinvasion. Int J Gynecol Pathol. 2012 Jul;31(4):337-43. doi: 10.1097/PGP.0b013e31823ff422. PMID: 22653347.
4. Murray SK, Young RH, Scully RE. Unusual epithelial and stromal changes in myoinvasive endometrioid adenocarcinoma: a study of their frequency, associated diagnostic problems, and prognostic significance. Int J Gynecol Pathol. 2003 Oct;22(4):324-33. doi: 10.1097/01.pgp.0000092161.33490.a9. PMID: 14501811.
5. Papanikolaou A, Kalogiannidis I, Goutzioulis M, Misailidou D, Makedos A, Vergote I, Makedos G. Pelvic lymphadenec-tomy as alternative to postoperative radiotherapy in high risk early stage endometrial cancer. Arch Gynecol Obstet. 2006 May;274(2):91-6. doi: 10.1007/s00404-006-0138-y. Epub 2006 Mar 4. PMID: 16518607.
6. Mohan DS, Samuels MA, Selim MA, Shalodi AD, Ellis RJ, Samuels JR, Yun HJ. Long-term outcomes of therapeutic pelvic lymphadenectomy for stage I endometrial adenocarcinoma. Gynecol Oncol. 1998 Aug;70(2):165-71. doi: 10.1006/gyno.1998.5098. PMID: 9740684.
7. Benedetti Panici P, Basile S, Maneschi F et al. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J. Natl Cancer Inst. 2008; 100; 1707–1716.
8. Kilgore LC, Partridge EE, Alvarez RD et al. Adenocarcinoma of the endometrium: survival comparisons of patients with and without pelvic node sampling. Gynecol. Oncol. 1995; 56; 29–33.

9. Cragun JM, Havrilesky LJ, Calingaert B et al. Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer. J. Clin. Oncol. 2005; 23; 3668–3675.
10. Alektiar KM, McKee A, Lin O et al. The significance of the amount of myometrial invasion in patients with Stage IB en-dometrial carcinoma. Cancer 2002; 95; 316–321.
11. Bottke D, Wiegel T, Kreienberg R, Kurzeder C, Sauer G. Stage IB endometrial cancer. Does lymphadenectomy replace adjuvant radiotherapy? Strahlenther. Onkol. 2007; 183; 600–604.
12. Keys HM, Roberts JA, Brunetto VL et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol. Oncol. 2004; 92; 744–751.
13. McKenney JK, Kong CS, Longacre TA. Endometri adenocarcinoma associated with subtle lymph-vascular space invasion and lymph node metastasis: a histologic pattern mimicking intravascular and sinusoidal histiocytes. Int. J. Gynecol. Pat-hol. 2005; 24; 73–78.
14. Naki MM, Oran G, Tetikkurt S, et al. Microcystic, elongated, and fragmented pattern of invasion in relation to histopat-hologic and clinical prognostic factors in endometrioid endometrial adenocarcinoma. Journal of the Turkish German Gynecological Association, 2017;18(3), 139.
15. Dogan Altunpulluk M, Kir G, Topal CS, et al. The association of the microcystic, elongated and fragmented (MELF) inva-sion pattern in endometrial carcinomas with deep myometrial invasion, lymphovascular space invasion and lymph node metastasis. Journal of Obstetrics and Gynaecology, 2015;35(4), 397-402.).
16. Choi, E. C., Kim, J. H., Kim, O. B., Byun, S. J., Park, S. G., & Kwon, S. H. (2012). Postoperative radiotherapy for endomet-rial cancer. Radiation oncology journal, 30(3), 108.
17. Kihara, A., Yoshida, H., Watanabe, R., Takahashi, K., Kato, T., Ino, Y., ... & Hiraoka, N. (2017). Clinicopathologic asso-ciation and prognostic value of microcystic, elongated, and fragmented (MELF) pattern in endometrial endometrioid carcinoma. The American journal of surgical pathology, 41(7), 896-905.
18. Chia VM, Newcomb PA, Trentham-Dietz A, et al. Obesity, diabetes, and other factors in relation to survival after endo-metrial cancer diagnosis. International Journal of Gynecologic Cancer, 2007;17(2).
19. Stewart CJR, Brennan BA, Leung YC, et al. MELF pattern invasion in endometrial carcinoma: association with low grade, myoinvasive endometrioid tumours, focal mucinous differentiation and vascular invasion. Pathology, 2009;41(5), 454-459.
20. Van den Heerik ASVM, Aiyer KTS, Stelloo E, et al. Microcystic elongated and fragmented (MELF) pattern of invasion: Molecular features and prognostic significance in the PORTEC-1 and -2 trials. Gynecol Oncol. 2022;166(3):530-537. doi:10.1016/j.ygyno.2022.06.027
21. Pavlakis K, Messini I, Vrekoussis T, et al. MELF invasion in endometrial cancer as a risk factor for lymph node metasta-sis. Histopathology, 2011,58(6), 966-973.
22. De Góis N, Martins NV, Abrão F, et al. Peritumorous lymph-vascular invasion, grade of histologic differentiation, and myometrial infiltration as prognostic factors of endometrial carcinoma. Revista paulista de medicina. 1993;111(3):385-90.
23. Gemer O, Arie AB, Levy T, et al. Lymphvascular space involvement compromises the survival of patients with stage I endometrial cancer: results of a multicenter study. European Journal of Surgical Oncology (EJSO). 2007;33(5):644-7.
24. Sanci M, Güngördük K, Gülseren V, et al. MELF pattern for predicting lymph node involvement and survival in grade I-II endometrioid-type endometrial cancer. International Journal of Gynecological Pathology, 2018;37(1), 17-21.
25. Quick CM, May T, Horowitz N S, et al. Low-grade, low-stage endometrioid endometrial adenocarcinoma: a clinicopat-hologic analysis of 324 cases focusing on frequency and pattern of myoinvasion. International journal of gynecological pathology, 2012;31(4), 337-343.
26. Prodromidou A, Vorgias G, Bakogiannis K, et al. MELF pattern of myometrial invasion and role in possible endometrial cancer diagnostic pathway: A systematic review of the literature. European Journal of Obstetrics & Gynecology and Reproductive Biology, 2018;230, 147-152.