Urinary cyclic GMP after treatment of gynecological cancer. A prognostic marker of clinical outcome.
BACKGROUND
The search for biological markers to predict malignant disease and its recurrence, or to monitor the effectiveness of treatment is a continuous process in medicine. Several years ago, urinary excretion of cGMP in urine was found to be a sensitive predictor in the follow-up of ovarian cancer and of monitoring treatment of cancer of the uterine cervix.


METHODS
In the present study, 27 patients with gynecological cancer, including cancer of the uterine cervix (n=13), cancer of the uterine corpus (n=8) and cancer of the ovaries (n=6), were monitored for 10 years. Blood and urinary samples were taken before primary treatment (baseline sample) and three months thereafter (three-month sample). The serum levels of CEA, CA-125 and PIIINP and urine excretion of cGMP and cAMP were determined. Creatinine levels in serum and urine were employed to determine renal clearance.


RESULTS
After 10 years' observation of women with cancer of the uterine cervix, seven patients showed no relapse and cGMP levels in baseline samples and three-month samples were 36.8+/-4.1 and 24.9+/-4.4 nmol cGMP/micromol creatinine (mean+/-SEM, p<0.01), respectively. The levels in patients (n=6) with relapse after 10 years' observation were 32.8+/-4.0 (baseline sample) and 43.5+/-4.2 (three-month sample) nmol cGMP/micromol creatinine (mean+/-SEM, p<0.02). Among the patients treated for cancer of the uterine corpus (n=9), none showed recurrent disease within the observation period of 10 years. The cGMP levels fell from 37.9+/-6.3 (baseline sample) to 22.3+/-2.3 (three-month sample) nmol cGMP/micromol creatinine (p<0.005). In the patients with ovarian cancer (n=6), 4 patients relapsed during the observation period of 10 years. In these women the cGMP levels increased from 34.5+/-2.7 (baseline sample) to 46.3+/-4.7 nmol cGMP/micromol creatinine whilst in both patients without relapse the levels decreased from 31.8 (range: 26.5-37.1) to 27.3 (range: 25.7-28.8) nmol cGMP/micromol creatinine, respectively. The changes in levels of cAMP, CEA, CA-125 and PIINP did not show statistically significant differences. Early changes in cGMP levels appear to predict long-term prognosis in gynecological cancers.
Orbo
Anne
A
Departments of Pathology, Faculty of Medicine, University of Tromsø, Norway.
Hanevik
Målfrid
M
Jaeger
Ragnhild
R
Van Heusden
Saskia
S
Sager
Georg
G
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine*; D018394:CA-125 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D000242:Cyclic AMP / Q000652:urine; D006152:Cyclic GMP / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D005833:Genital Neoplasms, Female / Q000097:blood / Q000628:therapy / Q000652:urine*; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000652:urine; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011379:Prognosis; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D002272:Carcinoembryonic Antigen; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D000242:Cyclic AMP; D006152:Cyclic GMP