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), -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 -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.