Correlation of molecular PSA subfractions with volume of benign and malignant prostate cancer tissue

317 INCREASING

THE SUCCESS

EXPULSION

RATE OF MEDICAL

OF DISTAL URETERAL

TREATMENT

WITH CALCIUM

STONES

CHANNEL

THERAPY

FOR

USING ADJUNCTIVE

BL.OCKER

P17

PROSTATECANCER:PSA,ANDROGENAND APOPTOSIS Friday,March 14,11.45-l 3.15 hrs, Room N113

CORRELATION VOLUME OF TISSUE

318

OF MOLECULAR PSA SUBFRACTIONS WITH BENIGN AND MALIGNANT PROSTATE CANCER

Steubcr 7.‘. Nurnukko I”. llaese A ‘. Pettersson K.‘. Hammerer P.‘. Iluland H.‘. LIIJ~ H

Skrekas T. Liapis D., Kalantris A.,Argyropoulos -1 General

Hospital “G.Gennimatas”.

lNTRODUCTlON

Urology.

& OBJECTIVES:

Athens,

Greece

The role of medical

of distal ureteral

of adjunctive

(nifedipine)

in the management

of distal ureteral atones.

& METHODS:

92 patients with radiopaquc

MATERIAL

I

and IVU. The patienta (27 males,

2

I

females,

(200mg/day), RESULTS:

with

was established

were randomised

19 females.

/day plus nifedipine males.

treatment

30mgiday median

channel

distal ureteral stones

by means of KUB, ultrasonography in two groups.

In group

age

31.8

In group A the average

with

38 patients

time 6 days (range

with average

clinical

years

old)

rccelvcd

stone size was 0,5 cm (0.3.0,8 cm) while in

2-12 days).

expulsion

CONCLUSIONS: rate of distal

examination,

KUB

and

were evaluated

ultrasonography.

26 patients

from group

time 18 days (14-23

B (56%)

At the

in both the stone free rate and expulsion

Adjunctive ureteral

therapy

with

stone (clcm)

nifedipinc

conservative

could

expulsion

were stone free

days). A statistically

significant

time. increase

‘University of Hamburg

Eppendorf, Department of Urology, I lamburg, Germany. liniversity of Turku. Department of Biotechnology. Turku. Finland. ‘MalmG University. Department of Climcal Chemistry. MalmB. Sweden

INTRODUCTION & OBJECTIVES: We mvestlgated the correlation of total PSA (tPSA), free PSA (fT’SA) and “Intact PSA” (PSA-I) with total prostate and transition done (tr) volume and with the amount of prostate cancer (PCs) nssue in patients with benign and malignant prostatic disease. MATERIAL&METHODS: Serum from men with negative systemanc biopsy (n=174) and biopsy proven prostate cancer (n-246) acre collected consecutively. ‘TPSA and fPSA were measured using a commercially available immunoassay. PSA-I wa, determined by a newly developed assay specific for the non-cleaved fPSA. “Nicked PSA” (PSA-N=fPSA-PSA-I) and complexed PSA (PSA-C=tPSA-fPSA) were calculated. Total prostate and tz- volume were measured using transrectal ultrasound. PCs volume was calculated using a computer assisted volumetric program. C’orrelatior uith volume wab performed by calculation of Speannan rank expressed as “rho” and simple regression for all patients and divided by diagnosis (non cancer and cancel group).

(25

only

nlmesulide

(83%) from group A were stone free with average

difference was observed

success

2OOmg

p.o. for IO days. In group B. 46 patients

for IO days ab well.

30 days

endpoint

A, 46 patients

nimesulide

group B the average size was 0,55cm (0,3-0,9 cm). All patients after

blocker

study (lasted from April 2000

age 43 years old) received

median

facilitating

We evaluated the

a calcium

cm were enrolled in a prospective

till May 2002). Diagnosis

therapy

is not well established.

the expulsion

effectiveness

smaller than

stones

A., Doumas K., Lycourinas M.

the

management.

RESUl,TS: For the whole study material. all analytes contributed Tigniticantly to benign prostate tissue volume (~‘0.05). Strong comzlatmns to prostate and tl- volume were obtained for tPSA (rho of 0.488 and 0.495, respectively) and its subfraction PSA-N (rho of 0.522 and 0.527. respectively) whereas there were weak correlations for tPSA (rho of 0.176 and 0. I X7, respectively). Wlthin the subgroup of patients without prostate cancer. total prostate volume correlation of fPSA and PSA-N was even higher (rho of 0.728 for tPSA and 0.700 for PSA-N). Regarding patients with PCs, all analytes contributed significantly to PCs volume (pcO.05): strongest correlation to cancer volume was observed for tPSA. PSA-C and PSA-I (rho of 0.495, 0.491 and 0.463, respectively). CONCLUSIONS:

PSA-N constitutes the fraction of fPSA that accounts most for benign of tT’SA and hence is a powerful indicator of nodular hyperplasic changes of the prostate. High correlation of PSA-I to the amount of PCs tissue in this ctudy is consistent with prewous reports showing PSA-I to he a more cancer specific subform of fPSA. Correlation of PSA-I with PCs volume was similar to the previously demonstrated correlation of hK2. The new mformatlon prowded by levels of PSA vubforms would be especially helpful In Identifying PCs lesions In large volume prostate glands.

volume

dependency

319

320

ANTITHROMBIN EXPRESSION IN THE MALIGNANT AND BENLGN PROSTATE: AN ANTI-ANGlOGENETIC FACTOR AND INHIBITOR OF PSA AND HK2

ANDROCENS REPRESS THE EXPRESSION OF THROMBOSPONDINI, AN INHIBITOR OFANGIOGENESIS, IN THE RAT PROSTATE AND IN HORMONE-RESPONSIVE HUMAN PROSTATE: CANCER

Bjartell A.‘. C’ao Y.‘. (iadaleanu

C‘olombel

V.‘. Lundwall

8.‘. I-&&_

‘Cinl\errity Hospital Malmii. Dept. of Urology. Malmii. S\\edcn. Malm& Dept. of ClimcalChemistry, Maim& Sweden

‘Um\ crsiiy lIo\p~tal

& OBJECTIVES: Antithrombm (Al ). a cermc protemase Inhibitor and important regulator of blood clottmg factors, was recently attributed anti-angiogenetlc and anti-proliferative effects on tumour cells in vitro. In the present study, we examined the expression of antlthrombin in benign and malignant prostate gland and functional aspects thereof.

M.‘. Foumier P.‘. Bou\ier

ricrriot [inI\ Lyon, France. Physlopathology.

R.‘. (‘ahon

F.‘. (‘lezardm

~iospiral. Urology. I-bon. tl-ante. ‘Inscrm. ‘Herriot Uni\. Hospital. Pathology. Lyon. Paris, France

I’.’ Phy~iollathologS. France. ‘Inscrm.

INTRODUCTION

MATERIAL & METHODS: Tissue mcroarrays of benign (n,50) and malignant (n>lSO) surgically resected prostatic specimens and prostate cancer cellines (LNCaP, PC-3, DU-145) were used for immunohistochemistry and in situ-hybridisation. SDSI’ACiE, Western Blots, and peptide substrale hydrolysis rate measurements wcrc employed to analyst free and complexed forms of AT, prostate-specific amigen (PSA) and human kallikrein-2 (hK2) in tissue extracts and in vitro Incubations ofAT/PSA or ATlhK2. RESULTS: Usmg immunohlstochemistry. antlthromhin way found in prostate epithelium and stroma cells. Tissue microarrays of turnours (n =I 12) and three different prostate cancer cell lines (PC-3. LNCaP and DU-145) were all positive for antithrombin. Abundant cxprcssion in a population of prostatic tumour cells was further evidenced by m situ hybridisation @xperiments. The nmnunostaining for antithrombin was confined to the cytoplasm, was most intense in Gleason grade 3 tumours and in part overlapped with that ofprostate-specific antigen. Western blotting of benign and mahgnant tissue homogenates revealed a predominant 58-kDa antithrombin immunoreactive component. In vitro, antithrombin formed complexes more readily with human kallikrein 2, particularly in the presence of heparin, and less efficiently with prostate-specific antigen. Both complexes could he recognized by polyclonal and monoclonal IgGs against antithrombin. CONCLUSIONS:

This is the first demonstration of expression and unmunolocalization ofAT in benign and malignant prostatic tissues and cell lines. AT is widely expressed in prostate cancer but is gradually lost in tumours of high Gleason grade. Antnhrombin inhibits the activity of hK2 and PSA in vitro and forms complexes with hK2 more efficiently than with PSA. The previously reported antiangiogenetic and anti-proliferative actions ofAT may be most relevant also in prostate cancer. as the expression is partially lost in poorly differentiated prostatic turnours.

European

Urology

Supplements

2 (2003)

No. 1, pp. 82

INTRODUCTION & OBJECTIVES: Thromhorpondm-I (TSP-I) IS a 450.kDa extracellular matrix protein that has been shown to suppress angiogencsis in viva. In this study, we demonstrate that androgens suppress the antiangiogemc activity of TSP- I in the normal and ncoplastic prostate. MATERIAL & METHODS: Different model were used in thts study: I ) the regeneration of the castrated rat ventral prostate during testosterone treatment to study prostate angiogenests and TSPI expression. 2) LNCaP prostate cancer cells using a luciferasc gene reporter ahsay were used as a functional analysis of the human TSP-I promoter region. 3) LNCaP tumour xenografts were used to assess the effects ofTSP-1 on tumour. 4) Human prostate cancer specimen (n = 103) with localized and advanced disease were used to examined TSP.1 expression and microvessel density. RESULTS: I) TSP-I was strongly expressed in the prostatic epithehum of castrated rats, coincidentally with the regression of’the vascularisation. However. its production in prostatic tissue was downregulated during vas@ar regrowth of the prostate under testosterone stimulation, suggesting a negative regulation of TSP.1 expression by androgens. 2) The functional analysis of hTSPl promoter revealed that an important androgen regulatory element(a) localized in the region of the first intron between positions +397 and +750 was responsible for the downregulation of TSP-I transcription induced by testosterone. 3) In nude mice. TSP-I expression led to a 60% tumour growth inhibition. 4) We found an inverse relationship between TSP- I immunoreactivity and microvessel density in patients with localized disease. More importantly. hormone-ablation therapy led to vascular regression and increase TSP-I expression in androgen-dependent invasive carcinomas. CONCLUSIONS: Collectively. these results strongly suggested that androgenablation therapy could induce the expression of the angiogenesis inhibitor TSP-1 in prostate carcinomas. The value of TSPl expression as a predictor of androgen response in high grade and mctastatic prostate cancer has to bc determine in further ytudiea.