A method to obtain reproducible Ki‐67 indices in lung adenocarcinoma

Abstract

Aims Proliferative activity, evaluated from the Ki‐67 index, is a strong prognostic factor in lung adenocarcinoma (LADC). Here, we optimised a procedure to measure the Ki‐67 index and establish the best cut‐off value. Methods and results We examined 342 stage I LADCs for the immunohistochemical expression of Ki‐67 using different antibodies, MIB1 and SP6. The results revealed the superior specificity of SP6; therefore, SP6 was used in subsequent analyses. Slides were scanned with a virtual slide system. Using software, tumour cells were counted in a whole tumour. Thereafter, the tumour was evenly subdivided into 0.25‐mm2 tiles. The frequency of positive cells was counted in each tile of an invasive area or the whole tumour. We calculated the number of tumour cells required to produce a 95% confidence interval (CI) <0.05. Additionally, we calculated coverage probabilities (CP) using two different methods, counting any number or 200 cells per tile. The results showed that we could meet our goal by counting 2000 cells from 10 random tiles (200 cells each) in invasive areas. Conclusions We successfully developed an optimal procedure for determination of the Ki‐67 labelling index using an SP6 antibody, which provided CP > 70% and CI of <0.05 in more than 90% of cases. Furthermore, we identified an optimal cut‐off value of 0.12 with an alternative of 0.15, based on disease recurrence. This procedure and the cut‐off values may be used in the routine pathological diagnosis of LADC.

Nomogram for the preoperative prediction of Ki-67 expression and prognosis in stage IA lung adenocarcinoma based on clinical and multi-slice spiral computed tomography features

“…Currently, the Ki-67 index is commonly regarded as a useful biomarker in clinical practice for predicting tumor cell proliferation, invasiveness, and prognosis and provides significant value in early lung cancer diagnosis and treatment assessment [ 21 , 22 ]. Recent research findings indicate that a Ki-67 index of 0.10–0.15 is a pivotal threshold for the proliferative activity of lung adenocarcinoma [ 20 ], suggesting a turning point toward higher tumor grades. Therefore, in this study, the Ki-67 threshold was set to 0.15 to categorize high and low expression levels.…”

“…The average percentage of positive cells among the total number of cells was quantitatively analyzed using the Ki-67 PI. The patients were categorized according to the Ki-67 labeling index (LI), with high and low Ki-67 LI defined as Ki-67 PI ≥ 15% and < 15%, respectively [ 20 ]. All pathological diagnoses were independently made by two pathologists.…”

Pre-operative Prediction of Ki-67 Expression in Various Histological Subtypes of Lung Adenocarcinoma Based on CT Radiomic Features

“…It has been reported that the overall survival (OS) and disease-free survival (DFS) of patients with high Ki-67 expression are shorter than those with low Ki-67 expression (5)(6)(7). Previous studies have identified the Ki-67 labeling index as a strong prognostic biomarker for lung adenocarcinoma (8,9). Yamashita et al found that Ki-67 can be used as an indicator of recurrence of lung cancer after resection (10), and the level of its positive expression is closely related to the differentiation degree, lymph node metastasis, and other factors of lung cancer (8,11).…”