KRAS mutation analysis in ovarian samples using a high sensitivity biochip assay.
BACKGROUND
Mutations in the KRAS gene are one of the most frequent genetic abnormalities in ovarian carcinoma. They are of renewed interest as new epidermal growth factor receptor (EGFR)-targeted therapies are being investigated for use in ovarian carcinoma. As KRAS mutations are associated with poor response and resistance to EGFR-targeting drugs, this study was conducted to obtain more information on the spectrum of KRAS mutations in ovarian carcinoma.


METHODS
The presence of KRAS mutations in codon 12 and 13 was analyzed in frozen and formalin-fixed paraffin-embedded (FFPE) tissue with a low density biochip platform. 381 malignant (29 borderline malignancy, 270 primary carcinomas, and 82 recurrent carcinomas) and 22 benign tissue samples from a total of 394 patients were examined. KRAS mutational status of each sample was correlated with dignity, FIGO stage, grade, histology, and survival.


RESULTS
KRAS mutations were found in 60 (15%) samples with 58 samples deriving from malignant tissue and 2 samples deriving from benign tissue. In 55 (92%) samples codon 12 was found to be mutated. Frozen and FFPE samples concurred with respect to KRAS mutation status.


CONCLUSIONS
KRAS mutation is a common event in ovarian cancer primarily in carcinomas of lower grade, lower FIGO stage, and mucinous histotype. The KRAS mutational status is no prognostic factor for patients treated with standard therapy. However, in line with experience from colorectal cancer and non-small-cell-lung cancer (NSCLC), it may be important for prediction of response to EGFR-targeted therapies.
Division of Gynaecology, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria. veronika.auner@meduniwien.ac.at
Veronika
V
Auner
Gernot
G
Kriegshäuser
Dan
D
Tong
Reinhard
R
Horvat
Alexander
A
Reinthaller
Alexander
A
Mustea
Robert
R
Zeillinger
D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis / Q000295:instrumentation / Q000379:methods* / Q000706:statistics & numerical data; D005260:Female; D005787:Gene Frequency; D006801:Humans; D009154:Mutation; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics*; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics*
D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins