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 1alpha (HIF1alpha) 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/l) and ovarian cystadenocarcinomas (383 +/- 116 IU/l) compared to healthy controls (256 +/- 68 IU/l) (p values 0.01 and 0.006, respectively). This difference did not reach significance in patients with breast cancer (328 +/- 169 IU/l; p = 0.17)). Uterine leiomyoma patients showed intermediate LDH levels (310 +/- 81 IU/l), while patients with breast fibroadenomas and ovarian cystadenomas had LDH serum levels close to carcinomas (308 +/- 60 and 348 +/- 135 IU/l, 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 HIF1alpha tissue expression was linked to high tissue LDH5 expression.


CONCLUSIONS
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.
Koukourakis
Michael I
MI
Departments of Radiotherapy/Oncology, Obstetrics/Gynaecology, Pathology, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
Kontomanolis
Emmanuel
E
Giatromanolaki
Alexandra
A
Sivridis
Efthimios
E
Liberis
Vassilios
V
D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics; D000328:Adult; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics; D003537:Cystadenoma / Q000097:blood / Q000235:genetics; D005260:Female; D018226:Fibroadenoma / Q000097:blood / Q000235:genetics; D005833:Genital Neoplasms, Female / Q000097:blood* / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000097:blood*; D007527:Isoenzymes / Q000096:biosynthesis / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis* / Q000097:blood*; D000080864:Lactate Dehydrogenase 5; D007889:Leiomyoma / Q000097:blood / Q000235:genetics; D015854:Up-Regulation
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5