Immunohistochemical evaluation of midkine and nuclear factor-κB as markers for diagnosis and prediction of synchronous metastasis in papillary thyroid cancer

Abstract

Objective Midkine(MK)and nuclear factor-kappa B(NF-κB)play pivotal roles in tumorigenesis, which are considered as promising cancer biomarkers. The efficacy of MK and NF-κB as markers for diagnosis and prediction of synchronous metastasis in papillary thyroid cancer(PTC)was the aim of present investigation. Methods Seventy six cases of PTC and seventy cases of multi-nodular goiter(MNG)were retrieved. The PTC group was further divided into subgroup 1(16 cases with synchronous metastasis)and subgroup 2(60 cases without metastases). A retrospective review of clinical information, radiological examinations, 131I treatments and post-131I-therapy scans were done. Immunohistochemistry of MK, NF-κB p65, and Ki-67 was performed on paraffin-embedded specimens and results were quantified. Diagnostic values of the parameters were conducted by receiver operating characteristic(ROC)curves. Diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were determined. Protein levels of MK and NF-κB p65 were then confirmed by Western blot. Results Immunoreactivities of MK and NF-κB p65, and positive percentage of Ki-67 were significantly higher in PTC group than in MNG group (all P<0.01). ROC showed good differential diagnostic capabilities of all three parameters with diagnostic accuracies of 82.192%, 80.137%, and 84.091% respectively. Moreover, all three parameters were significantly higher in subgroup 1 than those in subgroup 2 (all P<0.01). ROC showed good predicting efficacies in synchronous metastasis of all three parameters with diagnostic accuracies of 82.895%, 80.263%, and 76.316% respectively. By one-way analysis of variance, Western blot showed that MK and NF-κB p65 protein levels in lesions from subgroup 1 were significantly higher than those from subgroup 2, both were significantly higher than those in MNG lesions(P<0.01). Conclusion MK and NF-κB immunohistochemistry can potentially be used for differential diagnosis between PTC and MNG, and for prediction of synchronous metastases. Key words: Midkine; Nuclear factor-kappa B; Papillary thyroid cancer; Multi-nodular goiter