Kallikrein 4 is associated with paclitaxel resistance in ovarian cancer.
OBJECTIVE
Carcinoma of the ovary is the most fatal malignancy of the female genital tract in western countries. The effectiveness of chemotherapy is limited by the acquisition of drug resistance. Several members of the kallikrein (KLK) family were recently shown to be expressed in ovarian cancer and implicated in disease prognosis. One of these is KLK4, whose increased mRNA expression was identified as a poor prognostic marker in ovarian cancer. The goal of this study was to investigate if KLK4 protein (hK4) is expressed in ovarian carcinoma lesions and if it is associated with paclitaxel resistance.


METHODS
Immunohistochemistry was used to assess hK4 expression. The 126 lesions were from a cohort of 46 patients with platinum-resistant tumors, which were treated with weekly paclitaxel for recurrent disease. The overall response rate to weekly paclitaxel was 52% (24 of 46) and for patients with tumors resistant to standard three weekly paclitaxel treatment 48% (16 of 33).


RESULTS
Immunohistochemistry indicated that 85% (79 of 93) of lesions from paclitaxel-resistant patients expressed hK4, while only 61% (20 of 33) of lesions were positive for hK4 from paclitaxel sensitive patients. Statistical analysis showed that the intensity of hK4 staining was significantly associated with paclitaxel resistance (P = 0.005), whereas hK4 staining extent showed marginal significance (P = 0.05), but was significantly correlated with higher histological grade (P < 0.001).


CONCLUSIONS
These data show that hK4 is expressed in ovarian cancer and suggest that hK4 expression might be a predictive marker for paclitaxel resistance.
Xi
Zhijun
Z
Department of Biology, University of Oslo, Oslo, Norway.
Kaern
Janne
J
Davidson
Ben
B
Klokk
Tove Irene
TI
Risberg
Bjørn
B
Tropé
Claes
C
Saatcioglu
Fahri
F
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000096:biosynthesis*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D007610:Kallikreins; C120801:kallikrein 4; D017239:Paclitaxel