Mitogen-activated protein kinase signaling is activated in prostate tumors but not mediated by B-RAF mutations.
OBJECTIVE
A dysregulated mitogen-activated protein kinase (MAPK) pathway plays an important role in various malignancies and is often mediated by mutations in several oncogenes (eg, RAF, RAS). B-RAF mutations, predominantly the specific V600E mutation and additional alterations in exons 11 and 15, were frequently detected in malignant melanomas, papillary thyroid tumors, and colorectal cancers with microsatellite instability (MSI). The present study investigated B-RAF mutations, MSI status, and activation of MAPK signaling in prostate tumors.


METHODS
The V600E mutation of the B-RAF gene was analyzed using allele-specific polymerase chain reaction in 79 archival prostatic adenocarcinomas (pT1aG1 to pT3cG3, median Gleason score 6); exons 11 and 15 were sequenced. MSI status was determined using the National Cancer Institute consensus panel for hereditary nonpolyposis colorectal carcinoma (HNPCC) detection. Active MAPK signaling was investigated using immunohistochemistry for p44/ERK1 and p42/ERK2.


RESULTS
No B-RAF mutations could be detected. Six of 79 tumors showed MSI positivity. Active MAPK signaling was detected in 51% of the analyzed tumors. No correlation was found between MAPK activity and histopathologic/clinical characteristics.


CONCLUSIONS
The most frequent B-RAF gene alterations are not involved in prostate carcinogenesis. MSI is infrequent in prostate cancer and is not linked to B-RAF mutations. MAPK signaling is frequently activated in prostate tumors and might be suitable for a therapeutic approach.
Burger
Maximilian
M
Department of Urology, University of Regensburg, Germany.
Denzinger
Stefan
S
Hammerschmied
Christine
C
Tannapfel
Andrea
A
Maderstorfer
Armin
A
Wieland
Wolf Ferdinand
WF
Hartmann
Arndt
A
Stoehr
Robert
R
D000368:Aged; D000483:Alleles; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004789:Enzyme Activation; D005091:Exons / Q000235:genetics; D005260:Female; D015894:Genome, Human / Q000235:genetics; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D014633:Valine / Q000235:genetics
D004273:DNA, Neoplasm; D005973:Glutamine; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases; D014633:Valine