Quantitative Measurement of Progesterone Receptor Immunohistochemical Expression to Predict Lymph Node Metastasis in Endometrial Cancer

Abstract

Background: Previous studies have shown that loss of progesterone receptor (PR) in endometrial cancer (EC) is associated with poor outcomes. Evaluating lymph node metastasis (LNM) is essential, especially before surgical staging. The aim of this study was to investigate the role of PR expression and other clinicopathological parameters in LNM and to develop a prediction model. Methods: We retrospectively evaluated endometrioid-type EC patients treated with staging surgery between January 2015 and March 2020. We analyzed PR status using immunohistochemical staining, and the expression was quantified using the H-score. We identified optimal cut-off values of H-score and CA125 for predicting LNM using receiver operating characteristic curves, and used stepwise multivariate logistic regression analysis to identify independent predictors. A nomogram for predicting LNM was constructed and validated using bootstrap resampling. Results: Of the 310 patients evaluated, the optimal cut-off values of PR H-score and CA125 were 162.5 (AUC 0.670, p = 0.001) and 40 U/mL (AUC 0.739, p < 0.001), respectively. Multivariate analysis showed that CA125 ≥ 40 U/mL (OR: 8.03; 95% CI: 3.44–18.77), PR H-score < 162.5 (OR: 5.22; 95% CI: 1.87–14.60), and tumor grade 2/3 (OR: 3.25; 95% CI: 1.33–7.91) were independent predictors. These three variables were incorporated into a nomogram, which showed effective discrimination with a concordance index of 0.829. Calibration curves for the probability of LNM showed optimal agreement between the probability as predicted by the nomogram and the actual probability. Our model gave a negative predictive value and a negative likelihood ratio of 98.4% and 0.14, respectively. Conclusions: PR H-score along with tumor grade and CA125 are helpful to predict LNM. In addition, our nomogram can aid in decision making with regard to lymphadenectomy in endometrioid-type EC.

Estrogen/Progesterone Receptor Expression and Cancer Antigen 125 Level as Preoperative Predictors to Estimate Lymph Node Metastasis in Endometrioid Endometrial Cancer

“…In our previous study, we found that lower levels of PR expression, measured semiquantitatively, were associated with LNM. When incorporating PR expression into a prediction model with 2 other parameters, tumor grade and CA 125 levels, we demonstrated good prediction performance (9). The major concern was that the tissues we obtained for analysis were from hysterectomy specimens but not from pretreatment endometrial curettage.…”

“…Given that endometrioid ECs are typically hormone-dependent, and previous studies have shown that the loss of estrogen receptor/progesterone receptor (ER/PR) is associated with tumor progression and poor survival outcomes 8 , it is reasonable to investigate whether hormone receptor status could be a predictive parameter. We previously found that PR measurement in a semiquantitative manner, in conjunction with tumor grade and CA 125, could help estimate the probability of LNM 9 . However, the relationship between ER status and LNM has not yet been investigated, and the predictive value of ER status remains unclear.…”

The value of machine learning in preoperative identification of lymph node metastasis status in endometrial cancer: a systematic review and meta-analysis

“…Study types included case-control study and cohort study. Among them, there were only 10 cohort studies ( 28 , 35 , 39 , 49 , 51 – 53 , 62 – 64 ), 11 multicenter studies ( 26 , 30 , 33 , 45 , 46 , 60 – 64 , 66 ), and 1 study ( 40 ) from the SEER database, and the remaining studies were single-center studies. The median number of cases is 342 (IQR: 200~661), and the median number of cases in training sets is 300 (IQR: 154~533).…”