Does preoperative neutrophil to lymphocyte or platelet to lymphocyte ratios have a role in predicting borderline ovarian tumors?
© The Author(s). 2016
Received: 7 June 2016
Accepted: 18 October 2016
Published: 8 November 2016
to investigate the value of using preoperative neutrophil to lymphocyte and platelet to lymphocyte levels in the patients of borderline ovarian tumors.
During the period between January 2002 and December 2015, the pathology reports and archival files of the Gynecologic Oncology Department of Çukurova University Medical Hospital and the Gynecologic Oncology Department of Dumlupınar University, Evliya Çelebi Education and Research Hospital were retrospectively reviewed, and 144 patients of borderline ovarian tumor (as the study group) and 123 patients of serous cystadenoma (as the control group) were determined for eligibility in this study. Data regarding age, menopausal status, preoperative ultrasound findings, ca125 and complete blood counts were reviewed. Neutrophil to lymphocyte and platelet to lymphocyte ratios were calculated and these parameters were statistically compared between the groups.
There was a statistically significant difference between the groups according to neutrophil count, platelet count, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio; in addition to age, ca125 and preoperative ultrasound findings.
It seems that neutrophil to lymphocyte and platelet to lymphocyte ratios are useful in predicting borderline ovarian tumors, preoperatively. However, further prospective studies are needed.
Borderline ovarian tumors (BOTs) are characterized with atypical epithelial proliferation without stromal invasion and they comprise about 10–15 % of primary epithelial ovarian neoplasms . Compared with epithelial ovarian carcinomas (EOCs), BOTs are usually determined at early stages and presented in premenopausal women. Surgery is the mainstay of the treatment and frequently curable with excellent prognosis . Due to the absence of specific preoperative criteria for BOTs, diagnosis is often made by the pathological examinations of the surgical specimens. Findings of imaging methods and ca 125 measurements may indicate suspicious pelvic mass without specifying whether it is invasive or borderline tumor . Distinguishing these tumors (borderline or invasive) from the benign ones is extremely significant in order to skip over the incomplete surgery which results in poor prognosis .
Inflammation has a significant role in the development of numerous cancers by various mechanisms such as; up-regulation of cytokines and inflammatory mediators, inhibition of apoptosis, induction of angiogenesis and stimulation of DNA damage. In addition, immune function is compromised by systemic inflammatory response (SIR) mediators which then increase the leukocytes, neutrophils, platelets, C reactive protein (CRP) and fibrinogen concentrations. On the other hand, they decrease the lymphocyte level. Platelets can also be increased by the thrombocytosis induced by cancer. As preoperative inflammatory markers, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been suggested to be useful for discriminating malignant and benign ovarian tumors. NLR and PLR are noninvasive, easily measured, universally known and cost-effective markers [5–7].
To the best of our knowledge, although NLR and PLR levels (as preoperative markers) have been the subject of many studies concerning ovarian cancers, no specific studies associated with BOTs were found. Therefore, in the present study, we have aimed to investigate the value of using these markers prior to surgery in the patients of BOT.
This retrospective study was conducted at the Gynecologic Oncology Department of Çukurova University Medical Hospital in Adana, Turkey and the Gynecologic Oncology Department of Dumlupınar University, Evliya Çelebi Education and Research Hospital in Kütahya, Turkey. The study was approved by The Research Ethics Committee of Çukurova University. Gynecologic Oncology Unit records and pathology reports of the two centers were reviewed retrospectively for the period between 01 January 2002 and 30 December 2015. During this period, 116 cases from Çukurova University (ÇU) and 28 cases from Dumlupınar University (DPU); a total of 144 patients of BOT, and as control group a total of 123 patients of serous cystadenoma (98: from ÇU, 25: from DPU) were detected to be eligible for the study criteria. Clinical data such as age, menopausal status, preoperative ultrasound findings (presence of septa, papillary formation and ascites) ca125 and complete blood counts (CBC) were obtained from the hospital database network and archival files of the patients. Neutrophil, platelet, monocyte, hemoglobin and hematocrit parameters were attained from the CBC profile. These parameters were recorded separately and then NLR and PLR were calculated. The NLR was considered to be the absolute neutrophil count divided by the absolute lymphocyte count, and the PLR was defined as the absolute platelet count divided by the absolute lymphocyte count. Patients whose blood samples were not taken within a week before surgery were excluded from the study population. Also, patients with increased white blood cell count that might reflect a coexisting infection were not included. A story of hematological malignancies or other hematological and autoimmune disorders was the other exclusion criterion. According to the clinical and pathological assessments a total of 267 cases (study group: 144 BOT and control group: 123 serous cystadenoma) comprised the study population. Two groups were compared according to the aforementioned parameters.
Statistical methodology: Continuous variables were presented as mean, median and standard deviation (SD). Chi-square (χ 2) test evaluated associations between the categorical and continuous variables. Mann-Whitney U and Wilcoxon W tests were performed for the multiple comparisons between variables. The receiver operating characteristic (ROC) curve analysis was carried out to analyze the discriminative role of variables. P values were considered statistically significant at p < 0.05. SPSS 22.0 Evaluation Version (Statistical Package for Social Sciences, Chicago, IL, USA) software package was used for the statistical analysis.
Patients’ clinicopathological characteristics
In the preoperative assessment with ultrasonography; septa pattern was found to be positive in 78 (54.2 %) cases, papilla formation in 111 (77.1 %) and ascites in 35 (24.3 %) of the BOT patients. Nonetheless, all of these parameters were almost negative in the SCA group (p = 0,000). While the median of ca125 value was 86 (4–2878) in BOT patients, it was 25 (4–429) in the SCA group (p = 0,000).
Comparison of patients’ age, ca125 and hematologic variables between the groups
Preoperative assessment of an ovarian mass includes gynecologic examinations, imaging methods and tumor markers. Despite of all these tools, postoperative pathological evaluation is mandatory for the absolute diagnosis. Therefore, efforts are still made in order to obtain the ideal prediction of the mass nature. Risk of malignancy index (RMI) which includes ca125, ultrasound findings and menopausal status have been developed for this purpose. The increasing evidences emphasize the importance of inflammation in the initiation, promotion, invasion and metastasis of cancer . It was found that neutrophils increased and lymphocytes relatively decreased as a result of the systemic inflammatory response . Numerous studies have demonstrated the association between NLR and PLR with the ovarian cancers [4–6, 8]. In the current study, the association between NLR and PLR with BOTs has been investigated. A statistically significant impact for both of preoperative NLR (p = 0,000) and PLR (p = 0,039) in distinguishing BOTs from simple ovarian serous cysts was suggested, in this study. Beside, hemoglobin and hematocrit values, neutrophils, monocytes and platelets counts were evaluated and then compared separately between the groups. From these variables, merely monocytes count was not in a statistically significant manner. On the other hand, classic markers such as age, ca125 and ultrasound findings (septa, papillary pattern and ascites) were found to have statistically significant difference between the groups.
Topçu et. al. reported that they found statistically significant difference in term of age, diameter of the mass, ca125 levels, preoperative PLR and platelet count between the benign and malignant ovarian masses, whereas they didn’t find statistically significant effect in term of NLR . In the study by Yıldırım et. al. 316 benign and 253 malignant cases were assessed and preoperative NLR, PLR, and monocyte values were established to be higher in the malignant cases. Authors stated that NLR and PLR combined with CA-125 can be useful for benign-malignant differentiation of the ovarian masses . Cho et al. indicated that NLR is significantly increased in ovarian cancer cases. Moreover, it was supposed that NLR can identify CA-125-negative cases and predict poor outcome . NLR was showed to be associated with aggressive disease and poor survival in a retrospective study by Williams et al. of 519 ovarian carcinoma cases . PLR were also found to be elevated and correlated with poor prognosis and low survival rates in ovarian cancers by the study of Asher et. al. . Furthermore, Zhang and colleagues presumed that preoperative PLR was superior to the other SIR markers (CA-125, NLR, fibrinogen, CRP, and albumin) as a predictor of survival in ovarian cancer patients . Although several studies investigated the association between preoperative NLR and PLR with invasive ovarian cancers, to the best of our knowledge, there were no reported studies in the literature which researched these markers in the BOTs. Hence, it is deemed necessary to conduct the present study. A simple blood count is sufficient to provide these markers. These easily measured hematological variables were considered to be useful in discriminating BOTs from benign cysts preoperatively, in this study. Especially, NLR and PLR were fixed to be with an acceptable sensitivity and specificity values in terms of predicting borderline ovarian tumors, preoperatively. In addition, the difference between the study and control groups according to the classic predictors (age, ca125, ultrasound findings such as septa, papilla and ascites) was found to be statistically significant. Therefore, a novel model consisting of these classic predictors in combined with NLR and PLR values may be promising in identifying ovarian masses.
In conclusion, it seems that neutrophil to lymphocyte and platelet to lymphocyte ratios are useful in predicting borderline ovarian tumors, preoperatively. However, further prospective, large simple-size studies should be conducted on this subject.
Authors thank Professor Naki Tütüncü for editing the manuscript and Professor Gülşah Seydaoğlu for the statistical analysis.
No funding was received for this study.
Availability of data and material
GK conception of study, acquisition of data, revising the manuscript for intellectual content, approval of the final version, CS revising the manuscript for intellectual content, CÇ collecting data, approval of the final version, ÜKG revising the manuscript for intellectual content, ABG, approval of the final version, NK collecting data, approval of the final version, MAV revising the manuscript for intellectual content, approval of the final version, DG data analysis and interpretation, drafting the manuscript, approval of final version, All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
The study was approved by The Research Ethics Committee of Çukurova University. An informed consent was obtained from the participators.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Skirnisdottir I, Garmo H, Wilander E, Holmberg L. Borderline ovarian tumors in Sweden 1960-2005: trends in incidence and age at diagnosis compared to ovarian cancer. Int J Cancer. 2008;123:1897–901.View ArticlePubMedGoogle Scholar
- Shim SH, Kim SN, Jung PS, Dong M, Kim JE, Lee SJ. Impact of surgical staging on prognosis in patients with borderline ovarian tumours: a meta-analysis. Eur J Cancer. 2016;54:84–95.View ArticlePubMedGoogle Scholar
- Gotlieb WH, Soriano D, Achiron R, Zalel Y, Davidson B, Kopolovic J, et al. CA 125 measurement and ultrasonography in borderline tumors of the ovary. Am J Obstet Gynecol. 2000;183:541–6.View ArticlePubMedGoogle Scholar
- Topcu HO, Guzel AI, Ozer I, Kokanali MK, Gokturk U, Muftuoglu KH, et al. Comparison of neutrophil/lymphocyte and platelet/ lymphocyte ratios for predicting malignant potential of suspicious ovarian masses in gynecology practice. Asian Pac J Cancer Prev. 2014;15:6239–41.View ArticlePubMedGoogle Scholar
- Wang Y, Liu P, Xu Y, Zhang W, Tong L, Guo Z, et al. Preoperative neutrophil-to-lymphocyte ratio predicts response to first-line platinum-based chemotherapy and prognosis in serous ovarian cancer. Cancer Chemother Pharmacol. 2015;75:255–62.View ArticlePubMedGoogle Scholar
- Yildirim M, Demir Cendek B, Filiz Avsar A. Differentiation between benign and malignant ovarian masses in the preoperative period using neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios. Mol Clin Oncol. 2015;3:317–21.PubMedGoogle Scholar
- Zhang WW, Liu KJ, Hu GL, Liang WJ. Preoperative platelet/lymphocyte ratio is a superior prognostic factor compared to other systemic inflammatory response markers in ovarian cancer patients. Tumour Biol. 2015;36:8831–7.View ArticlePubMedGoogle Scholar
- Yildirim MA, Seckin KD, Togrul C, Baser E, Karsli MF, Gungor T, et al. Roles of neutrophil/lymphocyte and platelet/lymphocyte ratios in the early diagnosis of malignant ovarian masses. Asian Pac J Cancer Prev. 2014;15:6881–5.View ArticlePubMedGoogle Scholar
- Cho H, Hur HW, Kim SW, Kim SH, Kim JH, Kim YT, et al. Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment. Cancer Immunol Immunother. 2009;58:15–23.View ArticlePubMedGoogle Scholar
- Williams KA, Labidi-Galy SI, Terry KL, Vitonis AF, Welch WR, Goodman A, et al. Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer. Gynecol Oncol. 2014;132:542–50.View ArticlePubMedPubMed CentralGoogle Scholar
- Asher V, Lee J, Innamaa A, Bali A. Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin Transl Oncol. 2011;13:499–503.View ArticlePubMedGoogle Scholar