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Original Research

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The Ki-67 index and neutrophile-lymphocyte ratio are prognostic factors in patients with low-risk endometrial cancer

  • Erdem Cubukcu1
  • Ahmet Bilgehan Sahin1,*,
  • Fatma Oz Atalay2
  • Birol Ocak1
  • Mine Ozsen2
  • Candan Demiroz Abakay3
  • Kemal Ozerkan4
  • Ulviyya Hasanzade1
  • Merve Mesohorli1
  • Adem Deligonul1
  • Hakan Ozan4
  • Turkkan Evrensel1

1Department of Medical Oncology, School of Medicine, Bursa Uludag University, 16059 Bursa, Turkey

2Department of Pathology, School of Medicine, Bursa Uludag University, 16059 Bursa, Turkey

3Department of Radiation Oncology, School of Medicine, Bursa Uludag University, 16059 Bursa, Turkey

4Department of Gynecologic Oncology, School of Medicine, Bursa Uludag University, 16059 Bursa, Turkey

DOI: 10.31083/j.ejgo4204117 Vol.42,Issue 4,August 2021 pp.775-781

Submitted: 16 March 2021 Accepted: 21 April 2021

Published: 15 August 2021

*Corresponding Author(s): Ahmet Bilgehan Sahin E-mail: absahin@uludag.edu.tr; dr.absahin@icloud.com

Abstract

Objective: To investigate the prognostic factors comparing clinical, histopathological, and laboratory parameters in low-risk endometrial cancer (EC). Methods: In the present single-center study, multivariate Cox regression analysis was performed on retrospective clinical and laboratory data and histopathological features obtained from the re-evaluation of 253 patients with low-risk EC. Receiver operating characteristic curves (ROC) were plotted for neutrophile-lymphocyte ratio (NLR), platelet-lymphocyte ratio, lymphocyte-monocyte ratio and Ki-67 index for recurrence. Kaplan-Meier analysis was employed for survival rates. Results: The median age was 58.5 years (32.0–75.4). Most of the patients were obese and post-menopausal. In nearly half of the patients, lymphadenectomy was performed in addition to hysterectomy and oophorectomy. The median tumor size was 30 mm (range 2–80), and the median Ki-67 index was 25 (1–90). According to the ROC curve analysis, the cut-off values for the Ki-67 index, NLR, PLR, and LMR were determined as 22, 1.98, 115.3, and 4.71, respectively. The log-rank test revealed that the patients with a Ki-67 index lower than 22% and NLR lower than 1.98 had statistically longer recurrence-free survival (RFS) (p = 0.002 for Ki-67 index and p = 0.004 for NLR). The multivariate analysis revealed that the Ki-67 index and NLR were statistically significant factors for RFS (p = 0.012 and p = 0.029, respectively). Conclusion: The present study highlights the prognostic implications of both the Ki-67 index and NLR in low-risk EC.


Keywords

Endometrial cancer; Low-risk; Ki-67; NLR; Survival

Cite and Share

Erdem Cubukcu,Ahmet Bilgehan Sahin,Fatma Oz Atalay,Birol Ocak,Mine Ozsen,Candan Demiroz Abakay,Kemal Ozerkan,Ulviyya Hasanzade,Merve Mesohorli,Adem Deligonul,Hakan Ozan,Turkkan Evrensel. The Ki-67 index and neutrophile-lymphocyte ratio are prognostic factors in patients with low-risk endometrial cancer. European Journal of Gynaecological Oncology. 2021. 42(4);775-781.

References

[1] The International Agency for Research on Cancer. Global Cancer Observatory. 2020. Available at: https://gco.iarc.fr/ (Accessed: 24 January 2021).

[2] Constantine GD, Kessler G, Graham S, Goldstein SR. Increased incidence of endometrial cancer following the women’s health initiative: an assessment of risk factors. Journal of Women’s Health. 2019; 28: 237–243.

[3] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: A Cancer Journal for Clinicians. 2016; 66: 7–30.

[4] UptoDate. Endometrial cancer: Pathology and classification. 2020. Available at: https://www.uptodate.com/contents/endome trial-cancer-pathology-and-classification (Accessed: 24 January 2021).

[5] Colombo N, Creutzberg C, Amant F, Bosse T, González-Martín A, Ledermann J, et al. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: diagnosis, treatment and follow-up. Annals of Oncology. 2016; 27: 16–41.

[6] Togami S, Kawamura T, Yanazume S, Kamio M, Kobayashi H. Comparison of survival outcomes between laparoscopic and open surgery in patients with low-risk endometrial cancer. Japanese Journal of Clinical Oncology. 2020; 50: 1261–1264.

[7] Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H . Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. Journal of Immunology. 1984; 133: 1710–1715.

[8] Menon SS, Guruvayoorappan C, Sakthivel KM, Rasmi RR. Ki-67 protein as a tumour proliferation marker. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2019; 491: 39–45.

[9] Sun X, Kaufman PD. Ki-67: more than a proliferation marker. Chromosoma. 2018; 127: 175–186.

[10] Sobecki M, Mrouj K, Camasses A, Parisis N, Nicolas E, Llères D, et al. The cell proliferation antigen Ki-67 organises heterochromatin. ELife. 2016; 5: e13722.

[11] Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001; 357: 539–545.

[12] Bhatti I, Peacock O, Lloyd G, Larvin M, Hall RI. Preoperative hematologic markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil-lymphocyte versus platelet-lymphocyte ratio. American Journal of Surgery. 2010; 200: 197–203.

[13] Cupp MA, Cariolou M, Tzoulaki I, Aune D, Evangelou E, Berlanga-Taylor AJ. Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies. BMC Medicine. 2020; 18: 360.

[14] Nwachukwu C, Baskovic M, Von Eyben R, Fujimoto D, Giaretta S, English D, et al. Recurrence risk factors in stage IA grade 1 endometrial cancer. Journal of Gynecologic Oncology. 2021; 32: 1–10.

[15] Guan J, Xie L, Luo X, Yang B, Zhang H, Zhu Q, et al. The prognostic significance of estrogen and progesterone receptors in grade I and II endometrioid endometrial adenocarcinoma: hormone receptors in risk stratification. Journal of Gynecologic Oncology. 2019; 30: e13.

[16] Pinto de Andrade DA, Duval da Silva V, de Macedo Matsushita G, Alves de Lima M, de Andrade Vieira M, Cunha Andrade CEM, et al. Squamous differentiation portends poor prognosis in low and intermediate-risk endometrioid endometrial cancer. PLoS ONE. 2019; 14: 1–9.

[17] Moroney MR, Davies KD, Wilberger AC, Sheeder J, Post MD, Berning AA, et al. Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers. Gynecologic Oncology. 2019; 153: 517–520.

[18] Sasada S, Yunokawa M, Takehara Y, Ishikawa M, Ikeda S, Kato T, et al. Baseline risk of recurrence in stage I–II endometrial carcinoma. Journal of Gynecologic Oncology. 2018; 29: e9.

[19] Güngördük K, Firat Cüylan Z, Kahramanoglu I, Oge T, Akbayir O, Dede M, et al. Risk factors for recurrence in low-risk endometrial cancer: a case-control study. Oncology Research and Treatment. 2018; 41: 466–470.

[20] Cong R, Kong F, Ma J, Li Q, Wu Q, Ma X. Combination of preoperative neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and monocyte-lymphocyte ratio: a superior prognostic factor of endometrial cancer. BMC Cancer. 2020; 20: 464.

[21] Budak E, Kahraman DS, Budak A, Yanarateş A, Inan AH, Kanmaz AG, et al. The prognostic significance of serum CA125 levels with ER, PR, p53 and Ki-67 expression in endometrial carcinomas. Ginekologia Polska. 2019 ; 90: 675–83.

[22] Ellenson LH, Ronnett BM, Soslow RA, Zaino RJ, Kurman RJ. Endometrial Carcinoma. Blaustein’s Pathology of the Female Genital Tract. 2011; 257: 394–452.

[23] Kurman R, Carcangiu M, Herrington C YR. WHO classification of tumours of female reproductive organs. International Agency for Research on Cancer. 2014.

[24] Pavel M, Öberg K, Falconi M, Krenning EP, Sundin A, Perren A, et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2020; 31: 844–860.

[25] National Comprehensive Cancer Network. Breast Cancer. Version 1. 2021. Available at: https://www.nccn.org/professionals/p hysician_gls/pdf/breast.pdf (Accessed: 5 February 2021).

[26] National Comprehensive Cancer Network. Neuroendocrine and Adrenal Tumors. Version 2. 2020. Available at: https://www.nc cn.org/professionals/physician_gls/pdf/neuroendocrine.pdf (Accessed: 10 October 2020).

[27] Huvila J, Talve L, Carpén O, Edqvist P, Pontén F, Grénman S, et al. Progesterone receptor negativity is an independent risk factor for relapse in patients with early stage endometrioid endometrial adenocarcinoma. Gynecologic Oncology. 2013; 130: 463–469.

[28] Ferrandina G, Ranelletti FO, Gallotta V, Martinelli E, Zannoni GF, Gessi M, et al. Expression of cyclooxygenase-2 (COX-2), receptors for estrogen (ER), and progesterone (PR), p53, ki67, and neu protein in endometrial cancer. Gynecologic Oncology. 2005; 98: 383–389.

[29] Stefansson IM, Salvesen HB, Immervoll H, Akslen LA. Prognostic impact of histological and vascular invasion with tumour cell proliferation in endometrial carcinoma of endometrioid type. Histopathology. 2004; 44: 472–479.

[30] Suthipintawong C, Wejaranayang C, Vipupinyo C. Prognostic significance of ER, PR, Ki67, c-erbB-2, and p53 in endometrial carcinoma. Journal of the Medical Association of Thailand. 2008; 91: 1779–1784.

[31] Jia M, Jiang P, Huang Z, Hu J, Deng Y, Hu Z. The combined ratio of estrogen, progesterone, Ki‐67, and P53 to predict the recurrence of endometrial cancer. Journal of Surgical Oncology. 2020; 122: 1808–1814.

[32] Jiang P, Jia M, Hu J, Huang Z, Deng Y, Lai L, 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. Onco Targets Ther. 2020; 13: 10841–10850.

[33] Di Donato V, Iacobelli V, Schiavi MC, Colagiovanni V, Pecorella I, Palaia I, et al. Impact of hormone receptor status and Ki-67 expression on disease-free survival in patients affected by high-risk endometrial cancer. International Journal of Gynecological Cancer. 2018; 28: 505–513.

[34] Zhang Y, Zhao W, Chen Z, Zhao X, Ren P, Zhu M. Establishment and evaluation of a risk‐scoring system for lymph node metastasis in early‐stage endometrial carcinoma: achieving preoperative risk stratification. Journal of Obstetrics and Gynaecology Research. 2020; 46: 2305–2313.

[35] Salama A, Arafa M, ElZahaf E, Shebl AM, Awad AAE, Ashamallah SA, et al. Potential role for a panel of immunohistochemical markers in the management of endometrial carcinoma. Journal of Pathology and Translational Medicine. 2019; 53: 164–172.

[36] Kitson S, Sivalingam VN, Bolton J, McVey R, Nickkho-Amiry M, Powell ME, et al. Ki-67 in endometrial cancer: scoring optimization and prognostic relevance for window studies. Modern Pathology. 2017; 30: 459–468.

[37] Yang B, Shan B, Xue X, Wang H, Shan W, Ning C, et al. Predicting lymph node metastasis in endometrial cancer using serum CA125 combined with immunohistochemical markers PR and Ki67, and a comparison with other prediction models. PLoS ONE. 2016; 11: e0155145.

[38] Yu C, Jiang X, Li B, Gan L, Huang J. Expression of ER, PR, C-erbB-2 and Ki-67 in endometrial carcinoma and their relationships with the clinicopathological features. Asian Pacific Journal of Cancer Prevention. 2015; 16: 6789–6794.

[39] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144: 646–674.

[40] Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008; 454: 428–435.

[41] Wu L, Saxena S, Awaji M, Singh RK. Tumor-associated neutrophils in cancer: going pro. Cancers. 2019; 11: 564.

[42] Alexander NS, Matthew H. UptoDate. Principles of cancer immunotherapy. Available at: https://www.uptodate.com/content s/principles-of-cancer-immunotherapy (Accessed: 5 February 2021).

[43] Ni L, Tao J, Xu J, Yuan X, Long Y, Yu N, et al. Prognostic values of pretreatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in endometrial cancer: a systematic review and meta-analysis. Archives of Gynecology and Obstetrics. 2020; 301: 251–261.

[44] Aoyama T, Takano M, Miyamoto M, Yoshikawa T, Kato K, Sakamoto T, et al. Pretreatment neutrophil-to-lymphocyte ratio was a predictor of lymph node metastasis in endometrial cancer patients. Oncology. 2019; 96: 259–267.

[45] Kiuchi K, Hasegawa K, Ochiai S, Motegi E, Kuno T, Kosaka N, et al. Prognostic significance of inflammatory parameters and nutritional index in clinical stage IVB endometrial carcinomas. Journal of Obstetrics and Gynaecology. 2019; 39: 237–241.

[46] Holub K, Busato F, Gouy S, Sun R, Pautier P, Genestie C, et al. Analysis of systemic inflammatory factors and survival outcomes in endometrial cancer patients staged I–III figo and treated with postoperative external radiotherapy. Journal of Clinical Medicine. 2020; 9: 1441.

[47] National Comprehensive Cancer Network. Uterine Neoplasms. Version 1. 2021. Available at: https://www.nccn.org/professiona ls/physician_gls/pdf/uterine.pdf (Accessed: 25 January 2021).

[48] Murali R, Delair DF, Bean SM, Abu-Rustum NR, Soslow RA. Evolving roles of histologic evaluation and molecular/genomic profiling in the management of endometrial cancer. Journal of the National Comprehensive Cancer Network. 2018; 16: 201–209.


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