The noninvasive EFVPTC lesions having follicular growth patt

The noninvasive EFVPTC lesions having follicular growth pattern, particular microscopic architecture and nuclear features of PTC with low risk of malignancy have been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (Nikiforov et al., 2016; Strickland et al., 2016). The assessment of such borderline lesions is challenging for clinical practice as in this “grey zone” the intra-observer agreement may vary from 17% to 100% (Elsheikh et al., 2008). Recently Nikiforov et al. proposed diagnostic criteria for NIFTP which improved the overall diagnostic accuracy of NIFTP to 85.0–94.3% (Nikiforov et al., 2016). In EFVPTC, invasion rather than nuclear features influence tumor progression, patient management and prognosis (Ganly et al., 2015). Molecular testing may yield markers helpful in distinguishing invasive EFVPTC versus NIFTP where histological assessment of invasion is difficult or equivocal and ultimately may aid in differentiating these tumors by the fine needle aspirate (FNA) biopsy. Thus, ancillary methods to assess the invasive behavior of thyroid neoplasms are necessary to arrive at appropriate clinical decision to reduce the necessity of surgery and potential radioactive iodine (RAI) treatment. Biomarker-based ancillary screening may be a great asset in improving the diagnosis of NIFTP in pathology practice. Recently, we reported programmed cell death ligand 1 (PD-L1) expression on tumor cells correlated with poor prognosis in thyroid cancer (Chowdhury et al., 2016). PD-L1 is a ligand for Programmed cell death 1 (PD-1/B7-H1) receptor to function as negative immune regulator. PD-1 is expressed on the surface of lymphocytes, such as T cells, NU 7441 Supplier and natural killer T (NKT) cells. PD-L1 binding to PD-1 suppresses T-cell proliferation and cytokine release, such as IL-2 (Dong et al., 2002; Boussiotis, 2016). Its overexpression in a malignant neoplasm prevents malignant cells from being attacked by immune system due to a suppression of cytotoxic T cells. Thus, higher expression of PD-L1 in tumors will interfere with anti-tumor immunological attack and facilitate tumor growth and metastases. However, PD-L1 overexpression has not been examined to date to determine whether it can distinguish NIFTP from EFVPTC.
Materials and methods
Results
Discussion To our knowledge, this is the first report to demonstrate the use of a protein biomarker to objectively distinguish NIFTP from EFVPTC with invasion. The pathological criteria recommended by Nikiforov et al. (2016) for identifying NIFTP are based on morphological features and adequate sampling of the tumor capsule interface to exclude invasion. The assessment of the whole capsule and evaluation of invasiveness could be challenging in some cases (e.g. sharp tumor bud invades into but not through the capsule, follicles aligned perpendicular, mushroom-shaped tumor within but not through the capsule, partially preserved capsule, FNA biopsy cytology features (Maletta et al., 2016). The use of a protein biomarker PD-L1 expression, combining with histopathology, will facilitate an accurate distinction between NIFTP and EFVPTC with invasion and thereby aid in selection of NIFTP patients for lobectomy without RAI or observation only, and invasive EFVPTC management by completion thyroidectomy±RAI (Haugen et al., 2016). Recently, we reported increasing PD-L1 expression in thyroid cancer cells correlated with poor prognosis (Chowdhury et al., 2016). Upon binding to its specific receptor PD-1, it acts as an immune checkpoint regulator. This PD-L1/PD-1 pathway played a role in inhibiting T-cell receptor (TCR) mediated cell growth and cytokine production, resulting in peripheral tolerance of cancer cells and a failure to recognize and destroy the foreign cancer cells (Freeman et al., 2000; Blank et al., 2005; Okazaki and Honjo, 2007). Accordingly, the extent of PD-L1 expression on tumor cells largely emerges as a predictive biomarker in anti-PD-L1 directed cancer immunotherapy (Topalian et al., 2015). In the present study, we demonstrated that the expression of PD-L1 can be a predictor for distinguishing NIFTP from invasive EFVPTC.