Exploration of immunocytochemical biomarkers related to central lymph node metastasis in papillary thyroid microcarcinoma.

Abstract

Objective: The presence of central lymph node metastasis (CLNM) represents a critical determinant in ascertaining the necessity for surgical intervention in patients with papillary thyroid microcarcinoma (PTMC). However, the predominant current methodologies for confirming the central lymph node status in clinical practice are hampered by the low predictive accuracy of preoperative ultrasound examination and the high risk of preoperative fine needle aspiration (FNA). Consequently, the objective of this study is to investigate and identify specific immunocytochemical biomarkers for predicting CLNM in PTMC patients based on preoperative thyroid FNA samples.

Material and methods: In this study, the messenger ribonucleic acid sequencing data of pathological tumor stage 1 (pT1) papillary thyroid carcinoma (PTC) accompanied by pathological node stage information were initially retrieved from The Cancer Genome Atlas database. The differential expression genes (DEGs) between the pT1N1-PTC group and the pT1N0-PTC group were ascertained through bioinformatics methodology. Subsequently, these DEGs were imported into Cytoscape software to identify hub genes. Ultimately, immunohistochemical and immunocytochemical staining were employed to validate whether the biomarkers corresponding to the main hub genes demonstrated statistical significance in predicting CLNM within propensity score-matched PTMC samples.

Results: In this study, a total of 292 DEGs and 10 hub genes were successfully identified. Subsequently, immunohistochemical and immunocytochemical staining were conducted on 208 PTMC cases selected through propensity score matching. Among these 208 cases, the biomarkers (Cytokeratin 5/6 [CK5/6], Chromogranin A [CgA], and Pair box gene 2 [Pax-2]) corresponding to the main hub genes (Cytokeratin 5 [KRT5], Cytokeratin 6 [KRT6A], Chromogranin A [CHGA], and PAX2) were subjected to immunohistochemical staining in postoperative thyroidectomy specimens, the immunohistochemical staining results revealed a statistically significant difference in CK5/6 expression between PTMCs with and without CLNM (P = 0.002). Subsequently, CK5/6 immunocytochemical staining performed on preoperative thyroid FNA liquid-based samples further corroborated that CK5/6 expression was more prone to being positive in PTMCs with CLNM (P = 0.010).

Conclusion: CK5/6 is a valuable immunocytochemical biomarker capable of predicting the occurrence of CLNM in PTMC patients prior to surgery.