A Molecular Pathology Approach for Prostate Cancer Research : Application of the Laser Capture Micro-Dissection Technology - LMD
Coordinating Institution:
CRP Sante ,
Laboratoire National de Santé
Contracting Partner(s):
University of Luxembourg
Other Partner(s):
Institute for Biomedical Aging Research (A) ,
Tyrolean Cancer Research Institute
From: 01/11/2001
To: 28/02/2009
Budget: 1,100,000.00€
Contact(s):
Even Jos
Summary
One of the main goals of this projet is the establishment of a molecular pathology laboratory at the Laboratoire National de Santé (LNS) at the interface of pathologists, clinicians and researchers. Two topics were addressed.
1) The paper by Schmitz et al 2007 suggested that “Complete loss of PTEN expression as a potential early prognostic marker for prostate cancer metastasis”. These data needed to be confirmed by testing more samples in a more restricted patient population. Therefore, 154 prostate adenocarcinoma specimens obtained from patients first diagnosed more than 6 years ago selected according to Age <65, PSA< 10, Gleason score <4 were analysed for the expression of the anti-oncogene PTEN. 63.5% were found to be PTEN+, 15.4% PTEN- and 33% PTEN mixed (PTEN + and -). Contrarily to data obtained earlier no clear evidence was found in favour of PTEN expression loss alone as an early prognostic marker. The data will need to be re-evaluated taking into account more complete clinical data and fundamental research work clarifying the interactions of PTEN with other factors during oncogenesis.
2) In a pilot project 64 penile squamous cell carcinomas, obtained between 1980 and 2006 by the Division of Pathology at LNS were analysed for the presence of HPV sequences. 34 tumour blocks archived since 1992 could be used for DNA work using PCR based techniques. DNA from 26 out of 34 specimens obtained after 1992 could be used. 14 were HPV positive, 13 were high risk (9 HPV16, 3 HPV33 and 1 HPV52) and one was HPV11, a low risk type associated with condylomas. Thus in this small series 50% were positive for high risk HPV DNA. HPV16 derived PCR fragments were obtained using a protocol targeting E6, E7 and L1. the derived sequences revealed that 3 belonged to the European prototype HPV16 (EP-T350) and 5 belonged to the European variant (E-G350) Sequence variations, so far not listed in the databases, were found in two patients. This work is being completed by testing for E7, p16Ink4a and KI-67 protein expression.
After approximately one year of work in the new setting at the LNS the stage is set now for:
1) collaborative projects with colleagues from CRP-Santé and the University of Luxembourg using the Laser microdissection microscope.
2) a molecular epidemiology project to follow the evolution of the HPV types and sub-types in cervix carcinomas under the pressure of the recently licensed HPV vaccines.
Refereed Scientific Publications: --
Other Publications:
Etude de l’expression et de la localisation subcellulaire de PTEN dans l’adénocarcinome de la prostate à l’aide de biopsies et de lignées cellulaires humaines. Rapport de stage en laboratoire Master Vie et Santé Physiopatologie cellulaire et moléculaire Faculté de Pharmacie, Université Louis Pasteur Strasbourg
Figure : Immunohistochemistry: PTEN expression in prostate control tissues. A control staining was performed on a paraffin-embedded prostate tissue section showing a strong expression of PTEN in normal prostatic glands compared to adenocarcinoma cells.