Analysis of Factors Related to Lymph Node Metastasis in Early-Stage Type 1 Endometrial Cancer: Verifying the Clinical Value of Positive Threshold of the Immunohistochemical Parameter Ki67

Abstract

Objective Lymph node metastasis (LNM) is an important reference indicator for the prognosis of endometrial cancer (EC). Even in patients with early low-risk EC, many people still have LNM. The purpose of this study was to investigate the related factors influencing LNM in early-stage EC and determine the optimal positive threshold of immunohistochemical parameter Ki67 for predicting LNM, providing auxiliary reference indicators for clinical diagnosis and treatment. Methods The clinicopathological data of 651 patients with “apparent” early-stage EC who underwent standard surgical treatment were included. Univariate and multivariate logistics regression were used to analyze the correlation between each clinicopathological factor and LNM. Receiver operating characteristic curve (ROC curve) and Youden index were used to determine the optimal positive threshold of Ki67 for predicting LNM. Finally, correlation between Ki67 and various clinicopathological factors was analyzed, and the predictive value of each prognostic factor was compared. Results Multivariate analysis found that histologic grade (P=0.023), lymphatic vessel space invasion (LVSI) (P < 0.001), serological index Ca125 (P=0.002), immunohistochemical parameter Ki67 (P < 0.001), ER (P < 0.001) and P53 (P=0.001) were independent prognostic factors of LNM. ROC curve and Youden index showed that the optimal positive thresholds of Ki67 to predict LNM were 40%. Based on this, ROC curve showed that the area under the curve (AUC) of Ki67 (AUC=0.714) was larger than other single predictors, and Ki67 combined with other predictors can significantly increase the AUC value (AUC= 0.847 and 0.868, respectively). Conclusion Ki67 was an important predictor for predicting the LNM in early-stage EC and taking a positive percentage of about 40% can be used as the positive threshold of the immunohistochemical parameter Ki67. On this basis, Ki67 combined with other predictive indicators can significantly improve prediction performance and can be used for segmentally predicting LNM of early-stage EC.

A Nomogram Model for Predicting Recurrence of Stage I–III Endometrial Cancer Based on Inflammation-Immunity-Nutrition Score (IINS) and Traditional Classical Predictors

“…Immunohistochemical analysis of ER, PR, Ki67 and P53 was performed on an immunohistochemical autostainer (Leica Bond-Max, Milton Keynes, UK) according to an optimized and validated protocol of immunohistochemistry, the following mouse primary antibodies (ready-to-use) were used for immunohistochemistry: Ki67 (clone MX006), ER (clone SP1), PR (clone MX009), and P53 (clone MX008) (all purchased from Fuzhou, China, the specific experimental steps of immunohistochemistry can be seen in the references). 19,20 Pathological analysis (tumor site and size, histologic type and grade, the depth of myometrial invasion, the status of LVSI and cervical stromal invasion, etc.) were initially judged by primary physicians and reviewed by superior physicians.…”

“…21 Interpretation of immunohistochemical results refers to the following steps: 5 high-power fields were randomly observed in "hottest spot" area of tumor, and 100 tumor cells were assessed per field, tumor cells with strong nuclear immunostaining were defined as positive cells, then average percentages (range 0-100%) of positive cells of the five fields for each molecular maker (Ki67, ER, PR, and P53) were calculated. 19 This process was independently assessed by two experienced pathologists, and if the difference between the two observers' count results was ≤10%, the observations were considered consistent; otherwise, the results were reassessed (unblinded), and a consensus was reached. The average of the positive percentages assessed by two observers represented the final result of the immunohistochemical interpretation.…”

“…22 Referring to most other similar studies, ER and PR were defined as negative expression if the proportion of positive tumor cells of ER and PR was ≤5%; otherwise, ER and PR were defined as positive expression. 19,23 According to the results of our previous study, the proportion of positive tumor cells of Ki67 ≥40% and <40% were defined as high expression and low expression of Ki67, respectively. 19,21 According to the 3-stratified interpretation criteria of P53 immunohistochemistry, overexpression or complete loss of expression (no obvious positive tumor cell) of P53 was defined as abnormal (aberrant/mutation-type) expression, conversely, positive expression between the two extremes was defined as normal (wild-type) expression of P53.…”

Development and validation of a nomogram involving immunohistochemical markers for prediction of recurrence in early low-risk endometrial cancer

“…When >40% of tumor cells expressed Ki-67 ( + ), Ki-67 was defined as high expression. 16,21 According to Köbel et al, 22 the complete absence and overexpression were both regarded as P53 abnormal, whereas the wild-type pattern was considered P53 normal. (Supplementary Table 1).…”

Expression Profile and Molecular Basis of Cyclin-Dependent Kinases Regulatory Subunit 2 in Endometrial Carcinoma Detected by Diversified Methods

“…In current times, surgical operation consolidated by adjuvant chemotherapy and radiotherapy serves as the main treatment modality for endometrial carcinoma patients [6][7][8]. Although great progress made in the therapy of endometrial carcinoma has remarkably curbed the progression of endometrial carcinoma, endometrial carcinoma patients in later stage are still tortured by worsening prognoses, and recurrences were reported in some patients in the early stage [9,10]. Such a scenario highlights the imperative of seeking novel biomarkers and other treatment strategies.…”