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

  • Ji Young Park
  • Dae Gy Hong
  • Gun Oh Chong
  • Ji Y. ParkEmail author
Original Article

Abstract

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.

Keywords

Endometrial endometrioid carcinoma Tumor budding Prognosis Lymphovascular invasion Lymph node involvement 

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

Notes

Acknowledgements

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).

Compliance with Ethical Standards

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.

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Copyright information

© Arányi Lajos Foundation 2019

Authors and Affiliations

  • Ji Young Park
    • 1
  • Dae Gy Hong
    • 2
  • Gun Oh Chong
    • 2
  • Ji Y. Park
    • 1
    Email author
  1. 1.Department of Pathology, School of Medicine, Kyungpook National UniversityKyungpook National University Chilgok HospitalDaeguRepublic of Korea
  2. 2.Department of Obstetrics and Gynecology, School of Medicine, Kyungpook National UniversityKyungpook National University Chilgok HospitalDaeguRepublic of Korea

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