Ki-67 Index as a Prognostic and Diagnostic Marker in Follicular Neoplasm of Thyroid: A Systematic Review

Introduction: Ki-67 has shown promise as a predictive and diagnostic marker in solid tumours. The Ki-67 index is a wellestablished proliferation marker that has been studied in various tumours, including follicular neoplasms of the thyroid. Its role in thyroid pathology, especially in differentiating between Follicular Thyroid Adenoma (FTA) and Follicular Thyroid Carcinoma (FTC), has garnered significant clinical interest. Aim: To evaluate the diagnostic and prognostic utility of the Ki-67 labeling index (Ki-67 LI) in follicular neoplasms of the thyroid. Materials and Methods: A comprehensive search of records in the databases PubMed, Embase, and Scopus, along with manual citation searching, was conducted using MeSH terms and keywords related to ‘Ki-67 antigen’ and ‘FTC.’ Peerreviewed literature evaluating Ki-67 as a diagnostic or prognostic marker in follicular thyroid neoplasms published in English was included. Non English publications, reviews, case reports, and editorials, as well as research focusing solely on other thyroid cancers, including anaplastic or medullary carcinomas, were excluded during the screening process. The quality assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) Cochrane tool and the Quality in Prognosis Studies (QUIPS) for diagnostic and prognostic studies, respectively. A narrative synthesis and subgroup analysis of the extracted data were performed due to the heterogeneity in effect measures of Ki-67 labeling index and the outcomes. The parameters of prognostic outcomes assessed included the proportion of metastasis, recurrence, nodal involvement, survival rates, and mortality rates. The parameters of diagnostic outcomes involved the mean/median Ki-67 index to differentiate benign from malignant neoplasms. Results: A total of six eligible studies were included in this review. Follicular carcinomas demonstrated significantly higher Ki-67 labeling indices compared to adenomas. High values of Ki-67 are associated with malignancy, tumour aggressiveness, recurrence, and metastasis. The subgroup analysis indicated that the likelihood of poor prdeognosis for follicular thyroid neoplasms is approximately doubled at a cut-off of about 5% for the Ki-67 LI. Conclusion: This review includIntroduction: Ki-67 has shown promise as a predictive and diagnostic marker in solid tumours. The Ki-67 index is a wellestablished proliferation marker that has been studied in various tumours, including follicular neoplasms of the thyroid. Its role in thyroid pathology, especially in differentiating between Follicular Thyroid Adenoma (FTA) and Follicular Thyroid Carcinoma (FTC), has garnered significant clinical interest. Aim: To evaluate the diagnostic and prognostic utility of the Ki-67 labeling index (Ki-67 LI) in follicular neoplasms of the thyroid. Materials and Methods: A comprehensive search of records in the databases PubMed, Embase, and Scopus, along with manual citation searching, was conducted using MeSH terms and keywords related to ‘Ki-67 antigen’ and ‘FTC.’ Peerreviewed literature evaluating Ki-67 as a diagnostic or prognostic marker in follicular thyroid neoplasms published in English was included. Non English publications, reviews, case reports, and editorials, as well as research focusing solely on other thyroid cancers, including anaplastic or medullary carcinomas, were excluded during the screening process. The quality assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) Cochrane tool and the Quality in Prognosis Studies (QUIPS) for diagnostic and prognostic studies, respectively. A narrative synthesis and subgroup analysis of the extracted data were performed due to the heterogeneity in effect measures of Ki-67 labeling index and the outcomes. The parameters of prognostic outcomes assessed included the proportion of metastasis, recurrence, nodal involvement, survival rates, and mortality rates. The parameters of diagnostic outcomes involved the mean/median Ki-67 index to differentiate benign from malignant neoplasms. Results: A total of six eligible studies were included in this review. Follicular carcinomas demonstrated significantly higher Ki-67 labeling indices compared to adenomas. High values of Ki-67 are associated with malignancy, tumour aggressiveness, recurrence, and metastasis. The subgroup analysis indicated that the likelihood of poor prdeognosis for follicular thyroid neoplasms is approximately doubled at a cut-off of about 5% for the Ki-67 LI. Conclusion: This review included six studies involving retrospective analysis. There are variations in the techniques of immunohistochemical analysis, cell counting methods, and cut-off values chosen for the Ki-67 index among the included studies. Due to a lack of consensus regarding the reliability and standardisation of this biomarker, Ki-67 LI cannot replace standard histology. Regardless of a specific threshold, high Ki67 levels effectively differentiate carcinomas from adenomas and indicate a poor prognosis.ed six studies involving retrospective analysis. There are variations in the techniques of immunohistochemical analysis, cell counting methods, and cut-off values chosen for the Ki-67 index among the included studies. Due to a lack of consensus regarding the reliability and standardisation of this biomarker, Ki-67 LI cannot replace standard histology. Regardless of a specific threshold, high Ki67 levels effectively differentiate carcinomas from adenomas and indicate a poor prognosis.