Molecular and optical profiling of prostate tissues derived from populations with differential risk of prostate adenocarcinoma

Poster Abstracts Molecular and optical profiling of prostate tissues derived from populations with differential risk of prostate adenocarcinoma P.B. Singh, I.I. Patel, N. Ragavan, S.S. Matanhelia, F.L. Martin Lancashire Teaching Hospitals NHS Foundation Trust and Lancaster University, Preston and Lancaster, United Kingdom Aim: Exposure to environmental, dietary and/or hormonal carcinogens, and their biotransformation by metabolizing enzymes may account for the variable incidence of prostate adenocarcinoma (CaP) in different populations. We set out to examine whether there might be differences in quantitative expression of phase I and II metabolizing enzymes, aromatase and oestrogen receptor (ER) in prostate tissues obtained post-surgery from UKresident Caucasian compared to an India-resident Asian cohort. We examined the tissues’ chemistry using infrared (IR) spectroscopy. Material and methods: With ethical permission, verified-benign tissues were obtained following transurethral resection of the prostate from a high-risk region (n = 12 UK-resident Caucasians) and a low-risk region (n = 14 India-resident Asians). Quantitative gene expression analysis was employed for cytochrome P450 (CYP)1B1, N-acetyltransferase (NAT)1, NAT2, catecholO-methyltransferase (COMT), sulfotransferase (SULT)1A1, ER˛, ERˇ and aromatase (CYP19A1). Immunohistochemistry was carried out to quantify levels of CYP1B1, ER␣ or ER␤, and to identify their in situ localization. Chemical differences between prostate tissues from the two populations were interrogated by attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. IR spectra were subsequently processed in the biochemical-cell fingerprint region (1800—900 cm−1 ) employing principal component analysis-linear discriminant analysis (PCA-LDA) to minimize intra-category variance whilst facilitating the identification of biomarkers representing inter-category segregation. Results: Expression levels for the candidate genes investigated were similar. However, clear differences in protein levels for CYP1B1 and ER␤ were noted. Staining for CYP1B1 tended to be nuclearassociated in the basal glandular epithelial cells and in UK-resident Caucasian tissues was present at a significantly (P = 0.006) higher level compared to prostates from India-resident Asians. In contrast, a higher level of positive ER␤ staining was noted in prostates from India-resident Asians. Visualization of PCA-LDA scores plots and their corresponding

253 loadings plots pointed towards lipid (∼1736 cm−1 ), Amide I (∼1650 cm−1 ) and Amide II (∼1550 cm−1 ) as key discriminating factors between the low-risk (India) and high-risk (UK) cohorts. Conclusion: CYP1B1 and ER␤ may play an underlying role in disease progression in the prostate. Distinguishing factors in prostate tissues from different global regions using ATR-FTIR spectroscopy are identifiable. Whether these observations play a role in differential risk to CaP warrants further investigations. doi:10.1016/j.bjmsu.2009.09.004 A modified ‘rollerball’ technique for oncologically safe removal of distal ureter during laparoscopic nephroureterectomy M.A. Goldstraw, D.C. Hanbury, I. Dunn, J. Adshead The Lister Hospital, Stevenage, United Kingdom Introduction: We report our experience with a novel ‘rollerball’ technique for excising en bloc the bladder cuff and intramural lower ureter during laparoscopic nephroureterectomy (LN). Patients: This technique has been successfully performed in 7 patients with upper urinary tract TCC. Methods: A rigid cystoscope is passed and a small rollerball inserted into the lower end of the ureteric opening (UO). Rollerball diathermy (140 mV, 1 min) is performed to fuse the UO closed. Subsequently, a Collins knife is used to dissect around the UO through the detrusor muscle into the extravesical fat. A trans-abdominal LN can now be performed and the ureter dissected caudally into the pelvis placing two Weck clips at the distal end and the specimen removed. This technique has been proven watertight by saline irrigation to a pressure of 30 cm H2 O. Results: All catheters have been removed at day 5 with no postoperative complications. Final histopathological evaluation has revealed negative tumour margins at the distal ureteric margin in all cases with no recurrence on cystoscopy and CT follow-up (mean follow-up 32 months). Conclusion: We believe this technique seals the UO more effectively than oversewing without the morbidity associated with bivalving the bladder and adheres strictly to oncological principles. doi:10.1016/j.bjmsu.2009.09.005