Clinical laboratory features of Meigs’ syndrome: a retrospective study from 2009 to 2018

Abstract

Meigs’ syndrome (MS), a rare complication of benign ovarian tumors, is easily misdiagnosed as ovarian cancer (OC). We retrospectively reviewed the clinical laboratory data of patients diagnosed with MS from 2009 to 2018. Serum carbohydrate antigen 125 and HE4 levels were higher in the MS group than in the ovarian thecoma-fibroma (OTF) and healthy control groups (all P <0.05). However, the serum HE4 levels were lower in the MS group than in the OC group (P <0.001). A routine blood test showed that the absolute counts and percentages of lymphocytes were significantly lower in the MS group than in the OTF and control groups (all P <0.05). However, these variables were higher in the MS group than in the OC group (both P <0.05). The neutrophil-to-lymphocyte ratio (NLR) was also significantly lower, whereas the lymphocyte-to-monocyte ratio was higher in the MS group than in the OC group (both P <0.05). The NLR, platelet-to-lymphocyte ratio, and systemic immune index were significantly higher in the MS group than in the OTF and control groups (all P <0.05). The hypoxia-inducible factor-1 mRNA levels were also significantly higher, whereas the glucose transporter 1, lactate dehydrogenase, and enolase 1 mRNA levels were lower in peripheral CD4⁺ T cells obtained preoperatively in a patient with MS than those in patients with OTF, patients with OC, and controls (all P <0.05). The expression of these four glucose metabolism genes was preferentially restored to normal levels after the tumor resection of MS (P <0.001). These clinical laboratory features can be useful in improving the preoperative diagnostic accuracy of MS.

Keywords

Meigs’ syndrome / ovarian thecoma-fibroma / NLR (neutrophil to lymphocyte ratio) / CD4 ⁺ T cells / glucose metabolism

References

[1] Chechia A, Attia L, Temime RB, Makhlouf T, Koubaa A. Incidence, clinical analysis, and management of ovarian fibromas and fibrothecomas. Am J Obstet Gynecol 2008; 199(5): 473.e1–473.e4

[2] Sfar E, Ben Ammar K, Mahjoub S, Zine S, Kchir N, Chelli H, Khrouf M, Chelli M. Anatomo-clinical characteristics of ovarian fibrothecal tumors. 19 cases over 12 years: 1981–1992. Rev Fr Gynecol Obstet 1994; 89(6): 315–321 (in French)

[3] Sivanesaratnam V, Dutta R, Jayalakshmi P. Ovarian fibroma--clinical and histopathological characteristics. Int J Gynaecol Obstet 1990; 33(3): 243–247

[4] Meigs JV. Fibroma of the ovary with ascites and hydrothorax: Meigs’ syndrome. Am J Obstet Gynecol 1954; 67(5): 962–985

[5] Nicoll JJ, Cox PJ. Leiomyoma of the ovary with ascites and hydrothorax. Am J Obstet Gynecol 1989; 161(1): 177–178

[6] Meigs JV, Cass JW. Fibroma of the ovary with ascites and hydrothorax: with a report of seven cases. Am J Obstet Gynecol 1937; 33(2): 249–267

[7] Meigs JV. Fibroma of the ovary with ascites and hydrothorax: a further report. Ann Surg 1939; 110(4): 731–754

[8] Okuda K, Noguchi S, Narumoto O, Ikemura M, Yamauchi Y, Tanaka G, Takai D, Fukayama M, Nagase T. A case of Meigs’ syndrome with preceding pericardial effusion in advance of pleural effusion. BMC Pulm Med 2016; 16(1): 71

[9] Renaud MC, Plante M, Roy M. Ovarian thecoma associated with a large quantity of ascites and elevated serum CA 125 and CA 15-3. J Obstet Gynaecol Can 2002; 24(12): 963–965

[10] Timmerman D, Moerman P, Vergote I. Meigs’ syndrome with elevated serum CA 125 levels: two case reports and review of the literature. Gynecol Oncol 1995; 59(3): 405–408

[11] Morán-Mendoza A, Alvarado-Luna G, Calderillo-Ruiz G, Serrano-Olvera A, López-Graniel CM, Gallardo-Rincón D. Elevated CA125 level associated with Meigs’ syndrome: case report and review of the literature. Int J Gynecol Cancer 2006; 16(Suppl 1): 315–318

[12] Dong R, Jin C, Zhang Q, Yang X, Kong B. Cellular leiomyoma with necrosis and mucinous degeneration presenting as pseudo-Meigs’ syndrome with elevated CA125. Oncol Rep 2015; 33(6): 3033–3037

[13] Danilos J, Michał Kwaśniewski W, Mazurek D, Bednarek W, Kotarski J. Meigs’ syndrome with elevated CA-125 and HE-4: a case of luteinized fibrothecoma. Przegl Menopauz 2015; 14(2): 152–154

[14] Son CE, Choi JS, Lee JH, Jeon SW, Hong JH, Bae JW. Laparoscopic surgical management and clinical characteristics of ovarian fibromas. JSLS 2011; 15(1): 16–20

[15] Laganà AS, Vergara D, Favilli A, La Rosa VL, Tinelli A, Gerli S, Noventa M, Vitagliano A, Triolo O, Rapisarda AMC, Vitale SG. Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease. Arch Gynecol Obstet 2017; 296(5): 855–867

[16] Laganà AS, Colonese F, Colonese E, Sofo V, Salmeri FM, Granese R, Chiofalo B, Ciancimino L, Triolo O. Cytogenetic analysis of epithelial ovarian cancer’s stem cells: an overview on new diagnostic and therapeutic perspectives. Eur J Gynaecol Oncol 2015; 36(5): 495–505

[17] Bellia A, Vitale SG, Laganà AS, Cannone F, Houvenaeghel G, Rua S, Ladaique A, Jauffret C, Ettore G, Lambaudie E. Feasibility and surgical outcomes of conventional and robot-assisted laparoscopy for early-stage ovarian cancer: a retrospective, multicenter analysis. Arch Gynecol Obstet 2016; 294(3): 615–622

[18] Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140(6): 883–899

[19] Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454(7203): 436–444

[20] Margetts J, Ogle LF, Chan SL, Chan AWH, Chan KCA, Jamieson D, Willoughby CE, Mann DA, Wilson CL, Manas DM, Yeo W, Reeves HL. Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma? Br J Cancer 2018; 118(2): 248–257

[21] Sanchez-Salcedo P, de-Torres JP, Martinez-Urbistondo D, Gonzalez-Gutierrez J, Berto J, Campo A, Alcaide AB, Zulueta JJ. The neutrophil to lymphocyte and platelet to lymphocyte ratios as biomarkers for lung cancer development. Lung Cancer 2016; 97: 28–34

[22] Templeton AJ, Ace O, McNamara MG, Al-Mubarak M, Vera-Badillo FE, Hermanns T, Seruga B, Ocaña A, Tannock IF, Amir E. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2014; 23(7): 1204–1212

[23] Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, Leibowitz-Amit R, Sonpavde G, Knox JJ, Tran B, Tannock IF, Amir E. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 2014; 106(6): dju124

[24] Abramov Y, Anteby SO, Fasouliotis SJ, Barak V. Markedly elevated levels of vascular endothelial growth factor, fibroblast growth factor, and interleukin 6 in Meigs syndrome. Am J Obstet Gynecol 2001; 184(3): 354–355

[25] Abramov Y, Anteby SO, Fasouliotis SJ, Barak V. The role of inflammatory cytokines in Meigs’ syndrome. Obstet Gynecol 2002; 99(5 Pt 2): 917–919

[26] Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, Bordman Z, Fu J, Kim Y, Yen HR, Luo W, Zeller K, Shimoda L, Topalian SL, Semenza GL, Dang CV, Pardoll DM, Pan F. Control of T_H17/T_reg balance by hypoxia-inducible factor 1. Cell 2011; 146(5): 772–784

[27] Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, Chi H. HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of T_H17 and T_reg cells. J Exp Med 2011; 208(7): 1367–1376

[28] Liu G, Bi Y, Xue L, Zhang Y, Yang H, Chen X, Lu Y, Zhang Z, Liu H, Wang X, Wang R, Chu Y, Yang R. Dendritic cell SIRT1-HIF1a axis programs the differentiation of CD4⁺ T cells through IL-12 and TGF-b1. Proc Natl Acad Sci USA 2015; 112(9): E957–E965

[29] Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, Anderson SM, Abel ED, Chen BJ, Hale LP, Rathmell JC. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab 2014; 20(1): 61–72

[30] Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, Sullivan SA, Nichols AG, Rathmell JC. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4⁺ T cell subsets. J Immunol 2011; 186(6): 3299–3303

[31] Gerriets VA, Rathmell JC. Metabolic pathways in T cell fate and function. Trends Immunol 2012; 33(4): 168–173

[32] Buck MD, O’Sullivan D, Pearce EL. T cell metabolism drives immunity. J Exp Med 2015; 212(9): 1345–1360

[33] Chang CH, Qiu J, O’Sullivan D, Buck MD, Noguchi T, Curtis JD, Chen Q, Gindin M, Gubin MM, van der Windt GJ, Tonc E, Schreiber RD, Pearce EJ, Pearce EL. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell 2015; 162(6): 1229–1241

RIGHTS & PERMISSIONS

Higher Education Press