Tumor Budding is a Valuable Diagnostic Parameter in Prediction of Disease Progression of Endometrial Endometrioid Carcinoma

Recently, tumor budding (TB) found at the invasive margin has been related to lymph node involvement (LNI), local recurrence, and poor prognosis in various cancers. We assessed the presence of TB in endometrial endometrioid carcinoma (EEC), and examined the immunohistochemical (IHC) profiles to define its clinicopathological significance. Ninety-six EECs were obtained from 2008 to 2013. During the follow-up, ten patients experienced disease progression; of these, three patients succumbed to the disease. All hematoxylin and eosin-stained slides were scrutinized for the presence of TB. IHC stainings for estrogen receptor (ER), progesterone receptor (PR), β-catenin, and E-cadherin were performed. All cases were grouped as FIGO grade (G) 1 (47.9%), G2 (29.2%), and G3 (22.9%). The distribution for depth of invasion (DOI) was 68.5% with a DOI of less than half and 31.5% with a DOI of more than half. Myometrial invasion was characterized as infiltrating pattern (52.1%), adenomyosis-like (20.8%), microcystic, elongated, and fragmented (17.7%), or expansile (9.4%). TB was identified in 63 cases (65.6%). Lymphovascular invasion (LVI) and LNI were identified in 47 and 37 cases, respectively. TB was associated with deep DOI (p = 0.001), higher FIGO grade (p = 0.006), LVI (p < 0.0001), and LNI (p < 0.0001). TB showed loss of ER (p < 0.0001) and PR (p < 0.0001), reduced E-cadherin (p < 0.0001) expression, and aberrant β-catenin expression (p = 0.042). In EECs, TB was associated with deep DOI, less-differentiated histology, frequent LVI, and LNI; furthermore, TB was closely related to epithelial-mesenchymal transition phenotype and downregulation of hormonal receptors. Therefore, TB might be a determinant histologic clue for prediction of disease progression in EECs. Similar content being viewed by others Abbreviations - AM : - adenomyosis - DOI : - depth of invasion - EEC : - endometrial endometrioid carcinoma - EMT : - epithelial-mesenchymal transition - ER : - estrogen receptor - FIGO : - international federation of gynecology and obstetrics - IHC : - immunohistochemical - LN : - lymph node - LNI : - lymph node involvement - LUS : - lower uterine segment - LVI : - lymphovascular invasion - MELF : - microcystic, elongated, and fragmented - MI : - myometrial invasion - MPA : - medroxyprogesterone acetate - PR : - progesterone receptor

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This research was supported by Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (NRF-2017R1D1A1B03036519). Author information Authors and Affiliations Corresponding author Ethics declarations Ethical Approval and Informed Consent All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research board (KNUMCBIO_14–1008) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. Conflicts of Interest The authors declare that they have no conflict of interest. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Park, J.Y., Hong, D.G., Chong, G.O. et al. Tumor Budding is a Valuable Diagnostic Parameter in Prediction of Disease Progression of Endometrial Endometrioid Carcinoma. Pathol. Oncol. Res. 25, 723–730 (2019). https://doi.org/10.1007/s12253-018-0554-x Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s12253-018-0554-x