Advertisement

A more accurate method to interpret lactate dehydrogenase (LDH) isoenzymes’ results in patients with uterine masses

      Abstract

      Objective

      Since there are no approved reliable biomarkers for detecting preoperatively uterine sarcoma, lactate dehydrogenase (LDH) isoenzymes are usually required. We first evaluated the role of LDH isoenzymes in detecting uterine sarcoma risk, and then we tried to introduce a model to easily interpret the biochemical results.

      Methods

      We retrospectively retrieved records of patients who underwent surgical treatment for uterine masses from 2004 to 2016, and we compared data of 2211 patients with a definitive surgical diagnosis of uterine fibroids and 43 with uterine sarcomas. Quantitative relationships between serum LDH isoenzymes levels, as different single markers or in multiple assays, and the final diagnosis were investigated.

      Results

      LDH isoenzymes levels significantly differed between patients with benign uterine masses or sarcomas. LDH3 isoenzyme exhibited better predictive performances than the other four isoforms. Combining LDH3 with LDH1 isoenzymes into an inverse algebraic relationship, named Uterine mass Magna Graecia (U.M.G.) risk index, the accuracy of markers in discriminating between benign and suspicious malignant uterine masses was significantly enhanced, sensitivity at 100% and specificity at 99.6%, with nine false positive over 2211 benignant cases and no false negative over 43 sarcomas.

      Conclusions

      This retrospective analysis suggests to consider U.M.G. risk index as an inexpensive and accurate prognostic index that, once validated in a prospective study, may help clinicians in discriminating between benignant and suspicious malignant uterine masses.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      References

      1. Laparoscopic uterine power morcellation in hysterectomy and myomectomy: FDA safety communication.
        2014
        • Parker W.H.
        • Kaunitz A.M.
        • Pritts E.A.
        • et al.
        Leiomyoma Morcellation Review Group. U.S. Food and Drug Administration’s Guidance regarding morcellation of leiomyomas: well-intentioned, but is it harmful for women?.
        Obstet Gynecol. 2016; 127: 18-22
        • Parker W.H.
        • Pritts E.A.
        • Olive D.L.
        What is the future of open intraperitoneal power-morcellation of fibroids?.
        Clin Obstet Gynecol. 2016; 59: 73-84
        • Multinu F.
        • Casarin J.
        • Hanson K.T.
        • et al.
        Practice patterns and complications of benign hysterectomy following the FDA statement warning against the use of power morcellation.
        JAMA Surg. 2018; 11: e180141
        • Donnez J.
        • Donnez O.
        • Dolmans M.M.
        Safety of treatment of uterine fibroids with the selective progesterone receptor modulator, ulipristal acetate.
        Expert Opin Drug Saf. 2016; 15: 1679-1686
        • Donnez J.
        • Dolmans M.M.
        Uterine fibroid management: from the present to the future.
        Hum Reprod Update. 2016; 22: 665-686
        • Widy-Kierska K.
        • Roszkowski I.
        LDH isoenzymes in patients with uterine tumors.
        Obstet Gynecol. 1969; 33: 173-176
        • Nelson K.G.
        • Siegfried J.M.
        • Siegal G.P.
        • et al.
        DG. The heterogeneity of LDH isoenzyme patterns of human uterine sarcomas and cultured sarcoma cell lines.
        Am J Pathol. 1984; 116: 85-93
        • Kyriazoglou A.
        • Liontos M.
        • Ziogas D.C.
        • et al.
        Management of uterine sarcomas and prognostic indicators: real world data from a single-institution.
        BMC Cancer. 2018; 18: 1247
        • Mollo A.
        • Raffone A.
        • Travaglino A.
        • Di Cello A.
        • Saccone G.
        • Zullo F.
        • et al.
        Increased LDH5/LDH1 ratio in preoperative diagnosis of uterine sarcoma with inconclusive MRI and LDH total activity but suggestive CT scan: a case report.
        BMC Womens Health. 2018; 18: 169
        • Goto A.
        • Takeuchi S.
        • Sugimura K.
        • et al.
        Usefulness of Gd-DTPA contrast-enhanced dynamic MRI and serum determination of LDH and its isozymes in the differential diagnosis of leiomyosarcoma from degenerated leiomyoma of the uterus.
        Int J Gynecol Cancer. 2002; 12: 354-361
        • Di Cello A.
        • Borelli M.
        • Marra M.L.
        • et al.
        A new diagnostic algorithm for the management of uterine masses: the U.M.G. (Uterine mass Magna Graecia) risk score. ESGO7-1053 abstract.
        European Gynecological Oncology Congress, Vienna, Austria2017
      2. WHO Classification of Tumours.
        in: Kurman R.J. Carcangiu M.L. Herrington C.S. Young R.H. Volume 6 IARC WHO classification of tumours. 2014
        • Erickson R.J.
        Morales DR: clinical use of lactate dehydrogenase.
        N Engl J Med. 1961; 265: 478
        • R Core Team
        R: a language and environment for statistical computing.
        R Foundation for Statistical Computing, Vienna, Austria2014
        • Robin X.
        • Turck N.
        • Hainard A.
        • et al.
        pROC: an open-source package for R and S+ to analyze and compare ROC curves.
        BMC Bioinf. 2011; 12
        • Hothorn T.
        • Hornik K.
        • Zeileis A.
        Unbiased recursive partitioning: a conditional inference framework.
        J Comput Graph Stat. 2006; 15: 651-674
        • Kent Peter
        • Mark J.H.
        Interpretation of dichotomous outcomes: sensitivity, specificity, likelihood ratios, and pre-test and post-test probability.
        J Physiother. 2016; : 231-233
        • Miller K.D.
        • Siegel R.L.
        • Lin C.C.
        • et al.
        Cancer treatment and survivorship statistics.
        CA Cancer J Clin. 2016; 2016: 271-289
        • Rosenbaum L.
        N-of-1 policymaking-tragedy, trade-offs, and the demise of Morcellation.
        N Engl J Med. 2016; 374: 986-990
        • Adelman M.R.
        The morcellation debate: the history and the science.
        Clin Obstet Gynecol. 2015; 58: 710-717
        • Raine-Bennett T.
        • Tucker L.Y.
        • Zaritsky E.
        • et al.
        Occult uterine sarcoma and Leiomyosarcoma: incidence of and survival associated with morcellation.
        Obstet Gynecol. 2016; 127: 29-39
        • Kanade T.T.
        • McKenna J.B.
        • Choi S.
        • et al.
        Sydney contained in bag morcellation for laparoscopic myomectomy.
        J Minim Invasive Gynecol. 2014; 21: 981
        • Venturella R.
        • Rocca M.L.
        • Lico D.
        • et al.
        In-bag manual versus uncontained power morcellation for laparoscopic myomectomy: randomized controlled trial.
        Fertil Steril. 2016; 105: 1369-1376
        • Siedhoff M.T.
        • Wheeler S.B.
        • Rutstein S.E.
        • et al.
        Laparoscopic hysterectomy with morcellation vs abdominal hysterectomy for presumed fibroid tumors in premenopausal women: a decision analysis.
        Am J Obstet Gynecol. 2015; 212: 591
        • Hagemann I.S.
        • Hagemann A.R.
        • LiVolsi V.A.
        • et al.
        Risk of occult malignancy in morcellated hysterectomy: a case series.
        Int J Gynecol Pathol. 2011; 30: 476-483
        • Siedhoff M.T.
        • Cohen S.L.
        Tissue extraction techniques for leiomyomas and uteri during minimally invasive surgery.
        Obstet Gynecol. 2017; 130: 1251-1260
        • Desai V.B.
        • Guo X.M.
        • Xu X.
        Alterations in surgical technique after FDA statement on power morcellation.
        Am J Obstet Gynecol. 2015; 212: 685-687
        • Siedhoff M.T.
        • Wheeler S.B.
        • Rutstein S.E.
        • et al.
        Laparoscopic hysterectomy with morcellation vs abdominal hysterectomy for presumed fibroid tumors in premenopausal women: a decision analysis.
        Am J Obstet Gynecol. 2015; 212 (e1-8): 591
        • Rutstein S.E.
        • Siedhoff M.T.
        • Geller E.J.
        • et al.
        Cost-effectiveness of laparoscopic hysterectomy with morcellation compared with abdominal hysterectomy for presumed myomas.
        J Minim Invasive Gynecol. 2016; 1;23: 223-233
        • Venturella R.
        • Lico D.
        • Sarica A.
        • et al.
        OvAge: a new methodology to quantify ovarian reserve combining clinical, biochemical and 3D-ultrasonographic parameters.
        J Ovarian Res. 2015; 8: 8-21
        • Miao P.
        • Sheng S.
        • Sun X.
        • et al.
        Lactate dehydrogenase a in cancer: a promising target for diagnosis and therapy.
        IUBMB Life. 2013; 5: 904-910
        • Maekawa M.
        Lactate dehydrogenase isoenzymes.
        J Chromatogr. 1988; 429: 373-398
        • Seagle B.L.
        • Alexander A.L.
        • Strohl A.E.
        • et al.
        Discussing sarcoma risks during informed consent for nonhysterectomy management of fibroids: an unmet need.
        Am J Obstet Gynecol. 2017; 218 (e1-103.e5): 103