Contents lists available at ScienceDirect Annals of Diagnostic Pathology journal homepage: www.elsevier.com/locate/anndiagpath Original Contribution Role of P53, E-cadherin and BRAF as predictors of regional nodal recurrence for papillary thyroid cancer Khadiga M. Ali a, ⁎ , Shadi Awny b , Dina Abdallah Ibrahim a , Islam H. Metwally b , Omar Hamdy b , Basel Refky b , Ahmed Abdallah b , Khaled Abdelwahab b a Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt b Surgical Oncology, Oncology Centre Mansoura University, Mansoura, Egypt ARTICLE INFO Keywords: Regional nodal recurrence Papillary thyroid cancer P53 E-cadherin BRAF ABSTRACT Background: Regional nodal recurrence (RNR) in patients diagnosed with papillary thyroid carcinoma (PTC) has increased. Variable immunohistochemical (IHC) markers have been studied for predicting the likelihood of PTC for recurrence. We aimed to clarify the IHC expression of p53, Ecadherin and BRAF as potential markers of RNR in PTC. Method: 145 (73 study group and 72 control group) patients with PTC were analyzed retrospectively between January 2010 and June 2017. Further classification to a specific histological variant was done, and IHC ex- pression of p53, Ecadherin and BRAF was analyzed both in the primary tumor and in nodal recurrence. Results: Regarding the risk of RNR, we found certain clinicopathologic features as elder age ≥55 years, tumor size > 1 cm, presence of microscopic extrathyroid extension, presence of lymphovascular emboli, and conven- tional papillary subtype. Furthermore, IHC results for negative E-cadherin, and positive P53 and BRAF are significant risk factors, while radioactive iodine (RAI) adjuvant therapy decrease recurrence risk. Conclusion: We found several risk factors for RNR in PTC diagnosed patients, all of which are easily achievable in clinical settings. In this regard, we suggested that patients with specific clinicopathologic and im- munohistochemical features have strict follow up for early detection of RNR as it has a great impact on their survival. 1. Introduction Papillary thyroid carcinoma (PTC) is a well-differentiated thyroid carcinoma that originates from the thyroid follicular cells and accounts for 70–80% of all thyroid cancer [1]. The diagnosis of PTC is made mainly by the presence of certain nuclear features as nuclear grooves, clearing, overlapping, and pseudo-inclusions in addition to papillary architectural, but the latter is not necessary for the diagnosis [2]. Despite that PTC is of excellent prognosis with a 10-year survival rate of over 90%, its clinical behaviors are variable and complex. PTC spreads through lymphatics easily, that leads to tumor recurrence, distant metastases, and even death [3]. Recurrent PTC is variably interpreted either as primary tumor re- currence, lymph node metastases, invasion of the surrounding struc- tures as esophagus and trachea, or distant metastases [4]. Many factors as age, histologic subtype, staging, presence of extrathyroid invasion, and lymph node metastases, in addition to the primary surgery ap- proach are related to PTC recurrence, but final confirmation has not yet been done [5]. Many immunohistochemical (IHC) markers have been used for predicting prognosis in PTC. E-cadherin is an intercellular adhesion molecule that is completely expressed on the surface of the normal follicular cell's surface [6]. P53 is a well known tumor suppressor gene that controls different steps in cell cycle such as DNA repair, cell cycle arrest, differentiation, and apoptosis. P53 mutations could be seen in about 50% of the human cancers [7] in general and in 40–62% of un- differentiated thyroid carcinomas but in well-differentiated thyroid carcinomas, the mutations are only found in 0–25% [8]. BRAF is a member of the mitogen-activated protein kinase (MAPK) pathway that is associated with cell proliferation, cell differentiation, https://doi.org/10.1016/j.anndiagpath.2019.04.005 Abbreviations: FV PTC, follicular variant papillary thyroid cancer; PMC, papillary microcarcinoma; PTC, papillary thyroid cancer; RAI, radioactive iodine; RNR, regional nodal recurrence ⁎ Corresponding author at: Department of Pathology, Faculty of Medicine, Mansoura University, Elgomhoria Street, Mansoura, Eldakahliya 35516, Egypt. E-mail addresses: drdijamali@yahoo.com (K.M. Ali), shadiawny@mans.edu.eg (S. Awny), drislamhany@mans.edu.eg (I.H. Metwally), omarhamdy@mans.edu.eg (O. Hamdy), ahmedabdallah@mans.edu.eg (A. Abdallah). Annals of Diagnostic Pathology 40 (2019) 59–65 1092-9134/ © 2019 Elsevier Inc. All rights reserved. T