Serum and Tissue LDH Levels in Patients with Breast/Gynaecological Cancer and Benign Diseases

Background: Lactate dehydrogenase A (LDHA) is involved in anaerobic glycolysis. In cancer patients, serum total lactate dehydrogenase (LDH) levels are often increased, and the gene for one of its isoenzymes, LDHA, is up-regulated. These features have been linked to poor prognosis in several studies. Methods: We investigated comparatively the total serum LDH activity and tissue isoenzyme LDH5 and hypoxia-inducible factor 1 alpha (HIF1 alpha) levels in patients with breast (n = 18) and gynaecological (n = 23) malignancies and benign diseases (n = 54). Results: The serum LDH levels were significantly higher in patients with endometrial adenocarcinoma (349 +/- 100 IU/I) and ovarian cystadenocarcinomas (383 +/- 116 IU/I) compared to healthy controls (256 +/- 68 IU/I) (p values 0.01 and 0.006, respectively). This difference did not reach significance in patients with breast cancer (328 +/- 169 IU/I; p = 0.17)). Uterine leiomyoma patients showed intermediate LDH levels (310 +/- 81 IU/I), while patients with breast fibroadenomas and ovarian cystadenomas had LDH serum levels close to carcinomas (308 +/- 60 and 348 +/- 135 IU/I, respectively). LDH5 isoenzyme was strongly expressed in cancer cells, exhibiting a mixed cytoplasmic/nuclear subcellular pattern. Interestingly, a high LDH5 content in tissue sections was not invariably accompanied by high LDH serum levels. High HIF1 alpha tissue expression was linked to high tissue LDH5 expression. Conclusion: Serum and tissue LDH is up-regulated in gynaecologic and breast malignancies and in a subset of benign conditions such as fibro- and cystadenomas. The release of LDH, however, in the bloodstream is partly related to the LDHA gene up-regulation. Copyright (C) 2008 S. Karger AG, Basel