Total tissue lactate dehydrogenase activity in endometrial carcinoma S ˇ .S ˇ IMAGA*, M. ABRAMIC ´ *, M. OSMAKy, D. BABIC ´ z & J. ILIC ´ -FORKOz Divisions of *Organic Chemistry and Biochemistry and yMolecular Biology ‘‘RuCer Bos ˇkovi  c’’ Institute, Zagreb, Croatia; and zDepartment of Gynecological and Perinatal Pathology, University Hospital and School of Medicine Zagreb, Zagreb, Croatia Abstract. S ˇ imaga S ˇ , Abrami  c M, Osmak M, Babi  c D, Ili  c-Forko J. Total tissue lactate dehydrogenase activity in endometrial carcinoma. Int J Gynecol Cancer 2008. Lactate dehydrogenase (LDH) is essential for continuous glycolysis necessary for accelerated tumor growth. The aim of this study was to reconsider if assay of total tissue activity of this enzyme could be useful as marker for endometrial carcinoma (EC). Activity of LDH was measured spectrophotometrically in homoge- nate supernatants of uterine tissue samples of 40 patients (10 normal endometria, 27 normal myometria, and 33 EC), including 30 matched pairs. Data obtained were analyzed in relation to clinical and histopatho- logic findings and compared with our previously published results on the tissue levels of the same enzyme in ovarian cancer and on the proteolytic activity of dipeptidyl peptidase III (DPP III) in EC (suggested bio- chemical indicator of this malignancy). Significantly increased (1.8–3.0 times; P , 1 3 10 24 ) LDH activity was observed in EC samples if compared with normal uterine tissues. This rise was not related to the clini- copathologic findings, however. In contrast to previous results on LDH in ovarian carcinomas, a significant rise in LDH activity was found already in grade 1 EC. Using the cutoff value of 1.06 U/mg, diagnostic sen- sitivity of 82%, specificity of 100%, and accuracy of 91% for total tissue LDH assay have been calculated. A correlation of tissue’s LDH and DPP III activities was found, and their combined assay for EC showed increased diagnostic sensitivity (94%) and accuracy (96%). KEYWORDS: dipeptidyl peptidase III (DPP III), endometrial carcinoma, lactate dehydrogenase (LDH). Cancer of the corpus uteri is the eighth most common malignant neoplasm in women worldwide and endo- metrial cancer constitutes about 95% of all malignant lesions of uterine cavity (1) . The prevailing form of endometrial cancer is endometrial carcinoma (EC), tumor originating from the glandular epithelium of uterine endometrium. EC arises through a series of precursor lesions, which are thought to develop and be promoted in response to unopposed and prolonged stimulation by estrogen. On the other hand, some types of EC are estrogen independent (2) . EC is usually postmenopausal disease with peak incidence between age 50 and 60 years. Prognosis of EC is fairly good since overall 5-year survival rate is 83% and for the early stage of the disease, about 90% (1) . This is mainly due to early diagnosis indicated by abnormal bleeding and based on mandatory endometrial biopsy, which is strengthened by transvaginal ultrasonography, hys- teroscopy, vaginal and endometrial cytology, and bio- chemical clinical tests. One of these tests, assay of lactate dehydrogenase (LDH), is still under clinical evaluation in gynecological oncology. LDH [(S)-lactate:NAD 1 oxidoreductase Enzyme Commission 1.1.1.27], is one of the major glycolytic enzymes that catalyzes the last step of glycolysis, con- version of pyruvate to lactate. It is a tetrameric protein composed of two immunologically distinct subunits, ‘‘M’’ (muscle) and ‘‘H’’ (heart) type, which combine to form five isoenzymes (3) . LDH is ubiquitous cytosolic enzyme present in all tissues, exhibiting origin- and tissue-specific iso- enzymatic pattern (4) . Routine serum measurement of this enzyme is of clinical use in the diagnosis and monitoring of certain diseases including cancer, but is of low diagnostic value for gynecological malig- nancy (5) . In response to the need for more specific Address correspondence and reprint requests to: S ˇ umski S ˇ imaga, PhD, Division of Organic Chemistry and Biochemistry, ‘‘RuCer Bos ˇkovi  c’’ Institute, Bijenic ˇka 54, P.O. Box 180, 10002 Zagreb, Croatia. Email: simaga@irb.hr doi:10.1111/j.1525-1438.2008.01196.x # 2008, Copyright the Authors Journal compilation # 2008, IGCS and ESGO Int J Gynecol Cancer 2008