Glutathione S-transferases Pl-1 and Al-1 in ovarian cyst fluids

Purpose: The purpose of the present study was to determine the gluthathione S-transferases (GST) P1-1 and A1-1 levels in cyst fluid from malignant, borderline, and benign ovarian tumors. The clinical relevance of these enzymes in cyst fluid was investigated, including the possible relation with resistance to chemotherapy.

Methods: A total of 90 ovarian cysts were punctured for cyst fluid collection. GSTP1-1 and GSTA1-1 concentrations were determined by ELISA in cyst fluid from 23 malignant, 9 borderline, and 51 benign primary ovarian tumors, and levels were correlated with histopathological data.

Results: Significantly higher GSTP1-I concentrations were found in cyst fluid from malignant (median: 477 ng/ml), compared with benign (median: 52 ng/ml) ovarian cysts (p < 0.0001), as well as in fluid from borderline (median: 366 ng/ml) compared with benign cysts (p < 0.0001). No significant differences were found in cyst fluid GSTA1-1 concentrations between the histologic subgroups. In cyst fluid from malignant tumors higher GSTPI-1 and lower GSTAI-1 concentrations were found in patients with worse prognostic factors: FIGO II-III-IV, grade 2-3, residual tumor > 2 cm, presence of ascites, patients with recurrent disease, and survival, but differences were not significant. In the subgroup of patients that received cisplatin-based chemotherapy (n = 14) significantly higher GSTP1-1 (p = 0.01) concentrations were found in patients with recurrence compared with patients without recurrence. Considering only FIGO stage I patients, a differentiation could be made between patients with or without recurrence based on cyst fluid GSTP I - I concentrations.

Conclusions: Determination of glutathione S-transferases P 1-1 in cyst fluid samples from ovarian tumors can be of additiona] value in the differentiation between histologic subgroups. In case of possible low malignant potential cysts where sampling of the most representative tissue can be an issue, determination of GSTP- I concentrations in cyst fluid may optimise histopathologic classification. Cyst fluid GSTP1-1 seems to be a good marker for aggressiveness of the ovarian tumor, and it may predict response to chemotherapy.

Ovarian tumor; Cyst fluid; Glutathione S-transferase; Chemotherapy; Drug resistance

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