Ki-67 Labeling Index Is a Predictor of Postoperative Persistent Disease and Cancer Growth and a Prognostic Indicator in Papillary Thyroid Carcinoma

Abstract

Background: We previously reported that the Ki-67 labeling index (LI) in primary tumors and the thyroglobulin (Tg)-doubling time (DT) were potent prognostic indicators in patients with papillary thyroid carcinoma (PTC). Objectives: To elucidate the relationship between these two factors. Methods: A total of 390 patients with PTC who underwent total thyroidectomy between 1998 and 2004 and in whom the Tg-DT was calculated were enrolled. We determined the Ki-67 LI in primary tumors and compared these values with the patients' clinicopathological factors, postoperative Tg status, Tg-DT, and prognosis. Tg status was categorized by postoperative serum Tg values: biochemically persistent disease (BPD), equivocal state, and biochemical remission. Results: The Ki-67 LI was ≤5% in 312 patients (80%), 5%-10% in 48 patients (12%), and >10% in 30 patients (8%). Ki-67 LI was significantly associated with BPD (p < 0.0001). The proportion of BPD patients increased with the higher Ki-67 LI category: 24, 67, and 87%, respectively. The Ki-67 LI had a significant inverse correlation with the Tg-DT (Spearman's ρ = −0.5267, p < 0.0001). Of the 378 patients without distant metastasis at surgery, 68 patients had recurrence, and 6 of the 390 patients died of PTC during the follow-up (mean 88 months). On multivariate analyses, the Ki-67 LI remained an independent predictor of disease-free survival and disease-specific survival when Tg-DT and Tg status were excluded from the analyses. Conclusions: Evaluation of the Ki-67 LI in primary tumors may allow the prediction of the postoperative Tg status, Tg-DT and prognosis of patients with PTC.

Thyroid Cancers: Considerations, Classifications, and Managements

“…Tg-DT was recognized as an independent prognostic factor for both DFS and CSS of patients, whereas a short Tg-DT time (less than 1 year) is an indicator of poor prognosis. It was mentioned that Tg-DT is inversely linked to Ki-67 LI and so measurement of Ki-67 may give us information upon post-operative Tg status, Tg-DT, and prognosis of patients [37].…”

“…Ki-67 labeling index (LI) is generally low in PTC patients; however patients with high Ki-67 labeling index are more likely to show recurrence or persistent disease and to die from carcinoma [24,37]. High Ki-67 LI is considered as an independent prognostic factor for DFS and cause-speciic survival (CSS) [37,38].• BRAF V600E mutation: many previous studies have mentioned that PTC with BRAF mutation is more aggressive, associated with more recurrence, and has poorer prognosis [18,[39][40][41][42]. It has been shown that PTCs with BRAF V600E mutation and negative for X-linked inhibitor of apoptosis protein (XIAP) have higher chance of recurrence [18].…”

“…Tg-DT was recognized as an independent prognostic factor for both DFS and CSS of patients, whereas a short Tg-DT time (less than 1 year) is an indicator of poor prognosis. It was mentioned that Tg-DT is inversely linked to Ki-67 LI and so measurement of Ki-67 may give us information upon post-operative Tg status, Tg-DT, and prognosis of patients [37].Post-operative Tg status is also related to patients' age; so that a shorter Tg-DT (less than 2 years) is observed in old patients [45]. In conclusion, Tg-DT is a very convenient marker for the prediction of patients' prognosis in real-time and decision-making on use of molecular target agents.…”

“…Ki-67 labeling index (LI) is generally low in PTC patients; however patients with high Ki-67 labeling index are more likely to show recurrence or persistent disease and to die from carcinoma [24,37]. High Ki-67 LI is considered as an independent prognostic factor for DFS and cause-speciic survival (CSS) [37,38].…”

Prognosis and growth activity depend on patient age in clinical and subclinical papillary thyroid carcinoma [Review]

“…A high Ki-67 LI was found to be a prognostic factor for both the DFS and the CSS of PTC patients, and it was directly related to patient age [39,40]. BRAF V600E mutation is widely recognized as a strong prognostic marker for PTC in foreign countries [41,42], but in Japan, its prognostic value is limited [43,44].…”