title: Altered expression of Akt signaling pathway parameters in prostate needle biopsies derived from benign, adjacent and cancerous tissue.
abstract: PTEN, p-Akt and p27kip1 are known to be altered in prostate cancer. The aim of the present study was to determine the addition of molecular markers to a classical histopathological approach to enhance the sensitivity in detection of malignant or premalignant lesions within prostatic biopsies. Forty-two fine needle biopsies from malignant, tumor adjacent and benign areas were obtained from 14 patients scheduled for a prostatic biopsy. Biomarker expression was determined by immunohistochemistry and correlated to different localizations. We observed a reduction of Akt signaling proteins in cancer tissue compared to benign controls with significantly lower expression of p27kip1 (P=0.0024), PTEN (P=0.0045) and p-Akt (P=0.028). A pathologist histopathologically classified the tumor adjacent tissue obtained from areas distinctly apart from the primary tumor as benign in all cases. In these regions we observed an intermediate expression of Akt signaling proteins without significant difference in relation to the findings in the malignant samples. The expression of Akt signaling proteins is reduced in prostate cancer compared to normal prostate tissue. The intermediate expression of these proteins in tumor adjacent tissue warrants further investigations into the role of Akt signaling in the carcinogenesis and early detection of prostate cancer. There seems to be a marked difference between the molecular and histopathological characterization of prostate tissue. Molecular markers might further augment the histopathological diagnosis suggesting the need for earlier repeated prostate biopsy in case of microscopic malignancy.
authors.affiliation: Department of Urology, Hannover University Medical School, Hannover, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Waalkes
authors.forename: Perikles
authors.initials: P
authors.lastname: Simon
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Judith
authors.initials: J
authors.lastname: Knapp
authors.forename: Hossein
authors.initials: H
authors.lastname: Tezval
authors.forename: Jürgen
authors.initials: J
authors.lastname: Serth
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D016009:Chi-Square Distribution; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D010766:Phosphorylation; D011467:Prostate / Q000201:enzymology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis*; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human