Estrogen Receptor- And Progesterone Receptor-Positive Thresholds in Predicting the Recurrence of Early Low-Risk Endometrial Cancer

Background: Estrogen receptors (ER) and progesterone receptors (PR) have important prognostic value in endometrial cancer, but there is no recognized positive immunohistochemical threshold for predicting the recurrence of early low-risk endometrial cancer. The purpose of this study was to clarify the optimal positive thresholds of the immunohistochemical parameters the ER and PR in early low-risk endometrial cancer. Methods: A total of 332 patients with stage IA endometrial cancer were enrolled from the First Affiliated Hospital of Chongqing Medical University and People’s Hospital of Sha ping ba District in Chongqing between January 2013 and December 2018. First, univariate and multivariate Cox regression analyses were used to analyze the correlation between various clinical factors and the prognosis of early low-risk endometrial cancer. Then, the receiver operating characteristic curve (ROC curve) and Youden index were used to determine the positive thresholds of ER and PR. Results: The positive thresholds of ER and PR for predicting the recurrence of early low-risk endometrial cancer were 12% and 8%, respectively. Multivariate analysis showed that ER (P = 0.004), PR (P = 0.026), and p53 (P = 0.021) were risk factors for the prognosis of patients with early low-risk endometrial cancer. The recurrence-free survival and the overall survival in the low ER group and PR group were much lower than those in the high ER group and PR group (P < 0.001 of all). Conclusions: ER and PR positive thresholds of 12% and 8%, respectively, are the most suitable for predicting the recurrence of early low-risk endometrial cancer.

[1]  S. Kwiatkowski,et al.  Can the Determination of HE4 and CA125 Markers Affect the Treatment of Patients with Endometrial Cancer? , 2021, Diagnostics.

[2]  Zhen Huang,et al.  Prognostic Value of Ki67 in Patients with Stage 1–2 Endometrial Cancer: Validation of the Cut-off Value of Ki67 as a Predictive Factor , 2020, OncoTargets and therapy.

[3]  B. Weigelt,et al.  Clinical patterns and genomic profiling of recurrent ‘ultra-low risk’ endometrial cancer , 2020, International Journal of Gynecological Cancer.

[4]  E. Cicinelli,et al.  Conservative treatment in early stage endometrial cancer: a review , 2019, Acta bio-medica : Atenei Parmensis.

[5]  Shiney Kurian,et al.  Endometrial Cancer: An Overview of Pathophysiology, Management, and Care. , 2019, Seminars in oncology nursing.

[6]  M. Köbel,et al.  Interpretation of P53 Immunohistochemistry in Endometrial Carcinomas: Toward Increased Reproducibility , 2018, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[7]  H. Putter,et al.  Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial , 2018, The Lancet. Oncology.

[8]  Karl Garsha,et al.  Fully automated 5-plex fluorescent immunohistochemistry with tyramide signal amplification and same species antibodies. , 2017, Laboratory investigation; a journal of technical methods and pathology.

[9]  H. Chung,et al.  Prognostic factors for tumor recurrence in endometrioid endometrial cancer stages IA and IB , 2017, Medicine.

[10]  Weihong Song,et al.  Estrogen receptor α (ERα) status evaluation using RNAscope in situ hybridization: a reliable and complementary method for IHC in breast cancer tissues. , 2017, Human pathology.

[11]  C. Coutant,et al.  Patterns of recurrence and outcomes in surgically treated women with endometrial cancer according to ESMO-ESGO-ESTRO Consensus Conference risk groups: Results from the FRANCOGYN study Group. , 2017, Gynecologic oncology.

[12]  C. Coutant,et al.  Predicting poor prognosis recurrence in women with endometrial cancer: a nomogram developed by the FRANCOGYN study group , 2016, British Journal of Cancer.

[13]  J. Bakkum-Gamez.  Refining the Definition of Low-Risk Endometrial Cancer: Improving Value. , 2016, Gynecologic oncology.

[14]  Naoki Kagawa,et al.  Prognostic value of Ki67 and p53 in patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer: Validation of the cut-off value of the Ki67 labeling index as a predictive factor. , 2016, Molecular and clinical oncology.

[15]  H. Putter,et al.  Improved Risk Assessment by Integrating Molecular and Clinicopathological Factors in Early-stage Endometrial Cancer—Combined Analysis of the PORTEC Cohorts , 2016, Clinical Cancer Research.

[16]  C. Colombo,et al.  Impact of estrogen and progesterone receptor expression on the clinical and molecular features of papillary thyroid cancer. , 2015, European journal of endocrinology.

[17]  Wei Zhang,et al.  Prognostic role of hormone receptors in endometrial cancer: a systematic review and meta-analysis , 2015, World Journal of Surgical Oncology.

[18]  Caroline H. Diep,et al.  Progesterone action in breast, uterine, and ovarian cancers. , 2015, Journal of molecular endocrinology.

[19]  C. Mathers,et al.  Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 , 2015, International journal of cancer.

[20]  C. Coutant,et al.  Tumor Size, an Additional Prognostic Factor to Include in Low-Risk Endometrial Cancer: Results of a French Multicenter Study , 2015, Annals of Surgical Oncology.

[21]  H. Salvesen,et al.  Current Status of Molecular Biomarkers in Endometrial Cancer , 2014, Current Oncology Reports.

[22]  S. Goldman,et al.  Distribution of estrogen and progesterone receptors isoforms in endometrial cancer , 2014, Diagnostic Pathology.

[23]  J. Marcickiewicz,et al.  Hormone receptor loss in endometrial carcinoma curettage predicts lymph node metastasis and poor outcome in prospective multicentre trial. , 2013, European journal of cancer.

[24]  E. Laas,et al.  Histological and immunohistochemical profiles predict lymph node status in women with low-intermediate risk endometrial cancer. , 2013, Gynecologic oncology.

[25]  F. Pontén,et al.  Progesterone receptor negativity is an independent risk factor for relapse in patients with early stage endometrioid endometrial adenocarcinoma. , 2013, Gynecologic oncology.

[26]  F. Landoni,et al.  Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[27]  H.J.M.M. Mertens,et al.  Factors predicting recurrent endometrial cancer , 2013, Facts, views & vision in ObGyn.

[28]  E. Anteby,et al.  Temporal pattern of recurrence of stage I endometrial cancer in relation to histological risk factors. , 2012, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[29]  J. Schorge,et al.  Defining Prognostic Variables in Recurrent Endometrioid Endometrial Cancer: A 15-Year Single-Institution Review , 2011, International Journal of Gynecologic Cancer.

[30]  H. Putter,et al.  Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial , 2010, The Lancet.

[31]  S. Pecorelli.  Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium , 2009 .

[32]  T. Whelan,et al.  Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis , 2009, The Lancet.

[33]  Patrick Neven,et al.  Endometrial cancer. , 2005, Lancet.

[34]  C. Morrow,et al.  Relationship between surgical‐pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: A Gynecologic Oncology Group study , 1991, Gynecologic oncology.