Complete loss of PTEN expression as a possible early prognostic marker for prostate cancer metastasis.
The EGF/IGF growth factors are potent mitogens that regulate cell proliferation and cell survival and are involved in prostate cancer development. Using laser microdissection technology and real-time PCR, together with immunohistochemistry, we have explored the growth factor and integrin dependent PI3-kinase/PTEN/Akt signalling pathway in prostate cell lines and tumour samples by analysing EGF-R, IGF1-R, ILK, beta3 integrin, PTEN and p-Akt protein expression. We provide evidence that loss of PTEN expression rather than upregulated EGF/IGF1 receptor expression was responsible for increased p-Akt in neoplastic prostate cells. We therefore compared PTEN expression in patient biopsies at first time diagnosis recruited prospectively (Study I, 112 patients) and patients with confirmed metastasis recruited retrospectively from the Luxembourg cancer registry (Study II, 42 patients). In Study I, loss of PTEN expression at first time diagnosis was found in 26 of 112 patients (23%). In Study II, 25 of the 42 patients (59%) with lymph node metastasis had complete loss of PTEN expression in both the neoplastic glands of the prostate and the invasive prostate cancer cells in the lymph node, and of these 13 (52%) exhibited already loss of PTEN expression at first diagnosis. These findings demonstrate that loss of PTEN expression is an important factor in progression towards metastatic disease and could potentially serve as an early prognostic marker for prostate cancer metastasis.
Schmitz
Martine
M
Laboratoire de Biologie et Physiologie Intégrée (LBPI), Université du Luxembourg, 162A avenue de la Faïencerie, L-1511 Luxembourg.
Grignard
Gérard
G
Margue
Christiane
C
Dippel
Walter
W
Capesius
Catherine
C
Mossong
Joël
J
Nathan
Michel
M
Giacchi
Sandro
S
Scheiden
René
R
Kieffer
Nelly
N
D000230:Adenocarcinoma / Q000737:chemistry / Q000556:secondary*; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D039661:Integrin beta3 / Q000235:genetics; D008297:Male; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis; D011379:Prognosis; D011467:Prostate / Q000737:chemistry / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D014408:Biomarkers, Tumor; D039661:Integrin beta3; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human