Citation Information :
Nair IR, Rajanbabu A, Ambikakumari S, Kunneri B, Keechilat P. Evaluation of Morphological and Immunohistochemical Patterns Associated with MELF Type of Myoinvasion in Type I Endometrial Carcinomas. J South Asian Feder Obs Gynae 2022; 14 (5):505-509.
Introduction: Endometrial carcinomas constitute a variety of tumors with varied morphology and clinical outcome. Though type I carcinomas were found to have better prognosis, subsequent studies have shown that 5–10% of type-I carcinomas may recur or metastasize, thus shortening the overall survival. This has led to the search of additional factors which might predict adverse outcomes in these otherwise low-grade tumors. Several histological and immunohistochemical markers were studied and some of them were found to be significantly associated with lymph node metastasis, recurrence, and poor outcome.
Methods: In total, 50 cases of type-I, grade-1/2 endometrioid carcinomas were studied for microcystic, elongated, and fragmented (MELF) type of myoinvasion. About 23 cases showed MELF myoinvasion. The morphological and immunohistochemistry (IHC) pattern associated with MELF were studied. Their association with lymph node metastasis and survival was also noted. IHC done were cytokeratin (CK), CD44, progesterone receptor (PR), E-cadherin, and smooth muscle actin.
Results: Large tumor size, papillary pattern, and lymphovascular emboli (LVE) were associated with MELF. Among the IHC, expression of CD44 and loss of expression of PR and E-cadherin were found to be statistically significant. None of the cases showed lymph node metastasis on routine sections, however, ultrastaging was not done.
Conclusion: Morphological and IHC features differ between MELF-positive and -negative cases. There was no significant difference in survival between the MELF-positive and -negative cases.
Singh N, Hirschowitz L, Zaino R, et al. Pathologic prognostic factors in endometrial carcinoma (other than tumor type and grade). Int J Gynecol Pathol 2019;38(Suppl 1):S93–S113. DOI: 10.1097/PGP.0000000000000524.
Quick CM, May T, Horowitz NS, et al. Low-grade, low-stage endometrioid endometrial adenocarcinoma: A clinicopathologic analysis of 324 cases focusing on frequency and pattern of myoinvasion. Int J Gynecol Pathol 2012;31(4):337–343. DOI: 10.1097/PGP.0b013e31823ff422.
Cole AJ, Quick CM. Patterns of myoinvasion in endometrial adenocarcinoma: Recognition and implications. Adv Anat Pathol 2013;20(3):141–147. DOI: 10.1097/PAP.0b013e31828d17cc.
Elbasateeny SS, Salem AA, Abdelsalam WA, et al. Immunohistochemical expression of cancer stem cell related markers CD44 and CD133 in endometrial cancer. Pathol Res Pract 2016;212(1):10–16. DOI: 10.1016/j.prp.2015.10.008.
Zaino RJ. Unusual patterns of endometrial carcinoma including MELF and its relation to epithelial mesenchymal transition. Int J Gynecol Pathol 2014;33(4):357–364. DOI: 10.1097/PGP.00000000000 00137.
Murali R, Davidson B, Fadare O, et al. High-grade endometrial carcinomas: Morphologic and immunohistochemical features, diagnostic challenges and recommendations. Int J Gynecol Pathol 2019;38(Suppl 1):S40–S63. DOI: 10.1097/PGP.0000000000000491.
Stewart CJR, Brennan BA, Leung YC, et al. MELF pattern invasion in endometrial carcinoma: association with low grade, myoinvasiveendometrioid tumours, focal mucinous differentiation and vascular invasion. Pathology 2009;41(5):454–459. DOI: 10.1080/0031302090 3041135.
Campo L, Zhang C, Breuer E-K. EMT-inducing molecular factors in gynecological cancers. Biomed Res Int 2015: 420891. DOI: 10.1155/2015/420891.
Yorishima T, Nagai N, Ohama K. Expression of CD44 alternative splicing variants in primary and lymph node metastatic lesions of gynecological cancer. Hiroshima J Med Sci 1997;46(1):21–29. PMID: 9114564.
Liu YQ, Li HF, Han JJ, et al. CD44v3 and VEGF-C expression and its relationship with lymph node metastasis in squamous cell carcinomas of the uterine cervix. Asian Pac J Cancer Prev 2014;15(12):5049–5053. DOI: 10.7314/apjcp.2014.15.12.5049.
Leblanc M, Poncelet C, Soriano D, et al. Alteration of CD44 and cadherins expression: possible association with augmented aggressiveness and invasiveness of endometrial carcinoma. Virchows Arch 2001;438(1):78–85. DOI: 10.1007/s004280000269.
Gun BD, Bahadir B, Bektas S, et al. Clinicopathological significance of fascin and CD44v6 expression in endometrioid carcinoma. Diagn Pathol 2012;7:80. DOI: 10.1186/1746-1596-7-80.
Yadav A, Gupta A, Rastogi N, et al. Association of cancer stem cell markers genetic variants with gallbladder cancer susceptibility, prognosis, and survival. Tumour Biol 2016;37(2):1835–1844. DOI: 10.1007/s13277-015-3929-6.
Shen F, Gao Y, Ding J, et al. Is the positivity of estrogen receptor or progesterone receptor different between type 1 and type 2 endometrial cancer? Oncotarget 2017;8(1):506–511. DOI: 10.18632/oncotarget.13471.
Malpica A. How to approach the many faces of endometrioid carcinoma. Mod Pathol 2016;29(Suppl 1):S29–S44. DOI: 10.1038/modpathol.2015.142.
Scheuneman T, Maksem J, Genette S. 282 microcystic, elongated, and fragmented (MELF) pattern histology in FIGO grade 1 endometrial adenocarcinomas is associated with increased angiolymphatic and myometrial invasion. Am J Clin Pathol 2018;149(Suppl 1):S119–S120. DOI: 10.1093/ajcp/aqx123.281.
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. Int J Gynecol Pathol 2018;37(1):17–21. DOI: 10.1097/PGP.0000000000000370.
Kim CH, Soslow RA, Park KJ, et al. Pathologic ultrastaging improves micrometastasis detection in sentinel lymph nodes during endometrial cancer staging. Int J Gynecol Cancer 2013;23(5):964–970. DOI: 10.1097/IGC.0b013e3182954da8.