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MOLECULAR BIOLOGICAL ANALYSIS OF THE HETEROGENEOUS PROSTATE CANCER GROUP GLEASON SCORE 7
305
306
MOLECULAR BIOLOGICAL ANALYSIS OF THE HETEROGENEOUS
ADVERSE PATHOLOGICAL FINDINGS IN PATIENTS WITH NEEDLE BIOPSY GLEASON SCORE 6 PROSTATE CANCER WITH A PSA LEVEL OF 2-4NG/ML AND 4-10NG/ML FOLLOWING RADICAL PROSTATECTOMY
PROSTATE CANCER GROUP GLEASON SCORE 7 Mian C.1, Marziani F.1, Lodde, M.2, Comploj E.2, Palermo S.2, Lusuardi L.2, Mian M.2
Bektic J., Pelzer A.E., Berger A.P., Bartsch G., Horninger W.
1
General Hospital, Pathology, Bolzano, Italy, 2General Hospital, Urology, Bolzano, Italy INTRODUCTION & OBJECTIVES: Significant statistical difference in clinical outcome after radical prostatectomy between prostate cancer Gleason-Score 3+4 and 4+3 has been reported. On the basis of a multicolour-FISH test which was designed to detect and quantify chromosome 8, 8p22 and 8q24 we aimed at verifying whether there is any molecular biological background for the different behaviour of prostate cancer with Gleason-Score 7. MATERIAL & METHODS: Forty four patients (mean age 73.1 years, range 46-93) with histological verified prostate cancer were included in this study. 20 patients had biopsies with a Gleason score 3 + 4 (group A) and 24 a 4 + 3 (group B). 11 of the 44 patients underwent perineal prostatectomy after biopsy. All other patients were treated conservatively. Using fluorescence in situ hybridisation the chromosomal pattern of the biopsies was analysed.
Medical University Innsbruck, Dept. of Urology, Innsbruck, Austria INTRODUCTION & OBJECTIVES: Gleason score 6 prostate cancers are considered to be well differentiated tumours with a low risk for recurrence following therapy. In this study we investigated whether under-grading of biopsy Gleason score 6 in patients with a PSA level of 2-4 and 4-10 ng/ml following radical prostatectomy can results in adverse pathological findings. MATERIAL & METHODS: Data of 588 patients with a PSA level between 2.0 and 10.0ng/ mL who underwent radical prostatectomy between January 1995 and May 2004 were evaluated. Patients were stratified by preoperative PSA levels into two groups: low PSA (2-4ng/ml) and a PSA of 4-10ng/ml. The biopsy-Gleason scores were correlated with the final Gleason scores of the corresponding radical prostatectomy specimens and the incidence of adverse pathological findings (pathological stage pT3a or higher and positive surgical margins) in patients who remained Gleason score 6 was compared to the incidence when under-grading in the biopsy was observed.
RESULTS: A total of 30/44 (68.2%) prostate cancer cases were FISH positive. In 20 patients of group A (Gleason 3+4) FISH detected altogether 11 cases with aneusomy 8 (55.0%) with a gain of 8q24 in 2 patients (10.0%) and a loss of 8p22 in 9 patients (45.0%). No concurrent loss and gain of both sites was observed. of the 24 patients of group B (4+3) 20 patients showed aneusomy 8 (83.3%): 14 patients (58.3%) showed loss of 8p22 and 6 concurrent gain of 8q24 (25%). Two patients showed an amplification of c-myc.
RESULTS: Biopsy Gleason score 6 was found in 306 patients. of the cohort evaluated 50.6% (n=155) were identical, 29.7% (n=91) and 19.7% (n=60) were under- and over-graded in the biopsies, respectively. In patients who remained Gleason score 6 in the final prostatectomy specimens the incidence of extraprostatic disease (pathological stage ≥pT3a) was 4.6% and 5.7% in patients with low PSA (2-4ng/ml) and with a PSA of 4-10ng/ml, respectively. Undergrading in the biopsy results in a significantly (p<0.05) higher incidence of ≥pT3a tumours (13.2% at low and 28.3% at a PSA level of 4-10ng/ml). Positive surgical margins at low PSA were found in 9.3% and 15.7% (10.1% and 20.7% at a PSA level of 4-10ng/ml) of patients who remained Gleason score 6 and those who were under-graded in the final prostatectomy specimens, respectively.
CONCLUSIONS: There are different molecular genetic patterns between the two groups which explain the different biological behaviour. It might therefore be possible that in future the analysis of chromosomal aberrations could influence the clinical decision process.
CONCLUSIONS: The incidence of adverse pathological findings including extraprostatic extension and positive surgical margins is significantly higher in patients with under-graded biopsy Gleason score 6. Low preoperative PSA level improved the correlation between primary and finally Gleason score and has led to the reduction of unfavourable pathological findings.
307
308
ANTERIOR AND POSTERIOR T1C PROSTATE CANCER, CLINICAL AND HISTOPATHOLOGICAL CHARACTERISTICS OF 202 CASES
GRADE INFLATION IN PROSTATE CANCER THROUGHOUT 20 CONSECUTIVE YEARS OF RADICAL PROSTATECTOMY AT THE SAME INSTITUTION. IS THERE A REAL UPWARD SHIFT IN GRADE?
Arbeláez Arango S.1, Aguiló Lúcia F.1, Condom Mundó E.2, Suarez Novo J.1, Vigués Juliá F.1, Muñóz Segui J.1, Serrallach Mila N.1 1
Bellvitge Hospital, Dept. of Urology, Barcelona, Spain, 2Bellvitge Hospital, Dept. of Pathology, Barcelona, Spain INTRODUCTION & OBJECTIVES: Prostate cancer (PC) can originate in any zone of the prostate, its location may determinate evolution after treatment. Our aim was to know the clinical and histopathological characteristics of the different tumours according to its location within the gland. MATERIAL & METHODS: During four years a total of 202 open RRP for T1c PC were carried at our centre, none of the patients had had prior prostatic surgery, hormonal manipulation, external radiation or prostatic brachytherapy. All surgical specimens were review by a unique uropathologist. 1997 TNM system was use for staging. Clinical parameters at diagnosis, as well as biopsy and surgical specimen characteristics were analysed for each case. Maximum tumour diameter (MTD) was defined as the widest diameter of the main cancer focus present in the surgical specimen. Taking the urethra as longitudinal axis of reference, each case was assigned to be anterior, posterior or symmetrical according to where the 75% or more tumour volume was located. SPSS 9,0 software was use for statistical analysis. RESULTS: A total of 202 cases were analysed, 27 (13,4%) had anterior location, 136 (67,3%) had posterior location and 39 (19,3%) were symmetrical. Mean age for the three groups was 63,8 years. Mean serum PSA at diagnosis was of 8,8 ng/ml , a PSA significant difference was found between anterior and posterior tumours (p<0,001) and between anterior and symmetrical tumours(p=0,021) (12,0, 8,1 and 9,4 ng/ml respectively). 22,2% anterior tumours needed more than one biopsy session to be diagnosed while it only happened in 10,2% posterior tumours. A mean of 3,45 tumour-focus was found with no difference between groups. Anterior tumours presented a significantly greater MTD (p=0,038) than posterior tumours (2,72 vs. 2,26 cm respectively). Extraprostatic extension compromised different zones according to tumour location (Table 1). Stage distribution is shown in table 2. All pT4 cases had bladder neck affectation exclusively.
Salonia A.1, Zanni G.1, Scavini M.2, Freschi M.3, Montorsi F.1, Da Pozzo L.F.1, Scattoni V.1, Bertini R.1, Guazzoni G.1, Karakiewicz P.4, Rigatti P.1 1 Scientific Institute H. San Raffaele, Urology, Milan, Italy, 2Scientific Institute H. San Raffaele, Internal Medicine, Milan, Italy, 3Scientific Institute H. San Raffaele, Pathology, Milan, Italy, 4University of Montreal Health Center, Cancer Prognostics & Outcomes Research Unit, Montreal, Canada
INTRODUCTION & OBJECTIVES: To assess for presence of pathological grade shift in patients with prostate cancer (pCa) treated with RP over 20 years at the same academic institution. MATERIAL & METHODS: We reviewed all pathology records of n=4010 consecutive RP performed at our institution between 1984 and 2005. We abstracted patients’ age, date of surgery and Gleason score (GL). All cT1 to cT3 patients treated with RP also had a staging lymph node dissection. RESULTS: N=3925 records positive for adenocarcinoma were included in this analysis. Table 1 lists the pathological findings. Table 1 legend: a p<0.001 2001-2005 vs. 1991-1995 and 1996-2000; b p<0.006 vs. 1984-1990.
1984-1990
1991-1995
1996-2000
2001-2005
71
412
1023
2415
67.4 (12.1)
67.1 (9.2)
67.1 (9.5)
65.9 (9.9) a,b
GL<=6 (%)[95%CI]
57.4 [44.8, 69.3]
63.0 [58.1, 67.7]
61.8 [58.7, 64.9]
40.8 a,b[38.8, 42.8]
GL 7 [3+4] (%)
22.0 [12.9, 33.8]
15.3 [11.9, 19.2]
18.4 [16.0, 20.9]
29.3 a [27.4, 31.2]
GL 7 [4+3] (%)
7.4 [2.4, 16.3]
5.7 [3.6, 8.4]
10.2 [8.4, 12.3]
17.4 a [15.9, 19.0]
GL >=8 (%)
13.2 [6.2, 23.6]
16.0 [12.6, 20.0]
9.6 [7.8, 11.6]
12.5 [11.2, 13.9]
N Tab 1
Ant
Post
Sym
Apex
12(33,4)
31(30,1)
12(26,1)
Anterior
13(36,1)
2(1,9)
8(17,4)
Posterolateral
4(11,1)
67(65,1)
21(45,6)
B-N
7(19,4)
3(2,9)
5(10,9)
Tab 2
n(%)
Ant
Post
Sym
pT2a
n(%)
1(3,7)
11(8,1)
3(7,7)
pT2b
11(40,7)
56(41,2)
17(43,6)
pT3a
8(29,6)
52(38,2)
12(30,8)
pT3b
0 (0)
14(10,3)
2(5,1)
pT4
7(25,9)
3(2,2)
5(12,8)
CONCLUSIONS: PC with anterior location present a greater PSA at diagnosis, need more biopsies for diagnosis, have more tumour volume, and more bladder neck affectation than those with posterior or symmetrical tumour predominance. Using the urethra as longitudinal axis of reference is useful to classify prostate cancer as anterior, posterior or symmetrical.
Age in years [median (IQR)]
CONCLUSIONS: Our data confirm previously observed trends and indicate that grade at diagnosis shifted heavily toward pCa with moderate differentiation. Significantly reduced rates of welldifferentiated pCa are seen and the rates of poor prognosis disease are stable. Because assignment of GL score has been changing over time (namely, “the Will Rogers phenomenon”) and given that grade has an overwhelming impact on patient’s outcome, further studies are mandatory to evaluate whether a grade re-assignment could impact cancer control outcomes.
Eur Urol Suppl 2006;5(2):99
306
MOLECULAR BIOLOGICAL ANALYSIS OF THE HETEROGENEOUS
ADVERSE PATHOLOGICAL FINDINGS IN PATIENTS WITH NEEDLE BIOPSY GLEASON SCORE 6 PROSTATE CANCER WITH A PSA LEVEL OF 2-4NG/ML AND 4-10NG/ML FOLLOWING RADICAL PROSTATECTOMY
PROSTATE CANCER GROUP GLEASON SCORE 7 Mian C.1, Marziani F.1, Lodde, M.2, Comploj E.2, Palermo S.2, Lusuardi L.2, Mian M.2
Bektic J., Pelzer A.E., Berger A.P., Bartsch G., Horninger W.
1
General Hospital, Pathology, Bolzano, Italy, 2General Hospital, Urology, Bolzano, Italy INTRODUCTION & OBJECTIVES: Significant statistical difference in clinical outcome after radical prostatectomy between prostate cancer Gleason-Score 3+4 and 4+3 has been reported. On the basis of a multicolour-FISH test which was designed to detect and quantify chromosome 8, 8p22 and 8q24 we aimed at verifying whether there is any molecular biological background for the different behaviour of prostate cancer with Gleason-Score 7. MATERIAL & METHODS: Forty four patients (mean age 73.1 years, range 46-93) with histological verified prostate cancer were included in this study. 20 patients had biopsies with a Gleason score 3 + 4 (group A) and 24 a 4 + 3 (group B). 11 of the 44 patients underwent perineal prostatectomy after biopsy. All other patients were treated conservatively. Using fluorescence in situ hybridisation the chromosomal pattern of the biopsies was analysed.
Medical University Innsbruck, Dept. of Urology, Innsbruck, Austria INTRODUCTION & OBJECTIVES: Gleason score 6 prostate cancers are considered to be well differentiated tumours with a low risk for recurrence following therapy. In this study we investigated whether under-grading of biopsy Gleason score 6 in patients with a PSA level of 2-4 and 4-10 ng/ml following radical prostatectomy can results in adverse pathological findings. MATERIAL & METHODS: Data of 588 patients with a PSA level between 2.0 and 10.0ng/ mL who underwent radical prostatectomy between January 1995 and May 2004 were evaluated. Patients were stratified by preoperative PSA levels into two groups: low PSA (2-4ng/ml) and a PSA of 4-10ng/ml. The biopsy-Gleason scores were correlated with the final Gleason scores of the corresponding radical prostatectomy specimens and the incidence of adverse pathological findings (pathological stage pT3a or higher and positive surgical margins) in patients who remained Gleason score 6 was compared to the incidence when under-grading in the biopsy was observed.
RESULTS: A total of 30/44 (68.2%) prostate cancer cases were FISH positive. In 20 patients of group A (Gleason 3+4) FISH detected altogether 11 cases with aneusomy 8 (55.0%) with a gain of 8q24 in 2 patients (10.0%) and a loss of 8p22 in 9 patients (45.0%). No concurrent loss and gain of both sites was observed. of the 24 patients of group B (4+3) 20 patients showed aneusomy 8 (83.3%): 14 patients (58.3%) showed loss of 8p22 and 6 concurrent gain of 8q24 (25%). Two patients showed an amplification of c-myc.
RESULTS: Biopsy Gleason score 6 was found in 306 patients. of the cohort evaluated 50.6% (n=155) were identical, 29.7% (n=91) and 19.7% (n=60) were under- and over-graded in the biopsies, respectively. In patients who remained Gleason score 6 in the final prostatectomy specimens the incidence of extraprostatic disease (pathological stage ≥pT3a) was 4.6% and 5.7% in patients with low PSA (2-4ng/ml) and with a PSA of 4-10ng/ml, respectively. Undergrading in the biopsy results in a significantly (p<0.05) higher incidence of ≥pT3a tumours (13.2% at low and 28.3% at a PSA level of 4-10ng/ml). Positive surgical margins at low PSA were found in 9.3% and 15.7% (10.1% and 20.7% at a PSA level of 4-10ng/ml) of patients who remained Gleason score 6 and those who were under-graded in the final prostatectomy specimens, respectively.
CONCLUSIONS: There are different molecular genetic patterns between the two groups which explain the different biological behaviour. It might therefore be possible that in future the analysis of chromosomal aberrations could influence the clinical decision process.
CONCLUSIONS: The incidence of adverse pathological findings including extraprostatic extension and positive surgical margins is significantly higher in patients with under-graded biopsy Gleason score 6. Low preoperative PSA level improved the correlation between primary and finally Gleason score and has led to the reduction of unfavourable pathological findings.
307
308
ANTERIOR AND POSTERIOR T1C PROSTATE CANCER, CLINICAL AND HISTOPATHOLOGICAL CHARACTERISTICS OF 202 CASES
GRADE INFLATION IN PROSTATE CANCER THROUGHOUT 20 CONSECUTIVE YEARS OF RADICAL PROSTATECTOMY AT THE SAME INSTITUTION. IS THERE A REAL UPWARD SHIFT IN GRADE?
Arbeláez Arango S.1, Aguiló Lúcia F.1, Condom Mundó E.2, Suarez Novo J.1, Vigués Juliá F.1, Muñóz Segui J.1, Serrallach Mila N.1 1
Bellvitge Hospital, Dept. of Urology, Barcelona, Spain, 2Bellvitge Hospital, Dept. of Pathology, Barcelona, Spain INTRODUCTION & OBJECTIVES: Prostate cancer (PC) can originate in any zone of the prostate, its location may determinate evolution after treatment. Our aim was to know the clinical and histopathological characteristics of the different tumours according to its location within the gland. MATERIAL & METHODS: During four years a total of 202 open RRP for T1c PC were carried at our centre, none of the patients had had prior prostatic surgery, hormonal manipulation, external radiation or prostatic brachytherapy. All surgical specimens were review by a unique uropathologist. 1997 TNM system was use for staging. Clinical parameters at diagnosis, as well as biopsy and surgical specimen characteristics were analysed for each case. Maximum tumour diameter (MTD) was defined as the widest diameter of the main cancer focus present in the surgical specimen. Taking the urethra as longitudinal axis of reference, each case was assigned to be anterior, posterior or symmetrical according to where the 75% or more tumour volume was located. SPSS 9,0 software was use for statistical analysis. RESULTS: A total of 202 cases were analysed, 27 (13,4%) had anterior location, 136 (67,3%) had posterior location and 39 (19,3%) were symmetrical. Mean age for the three groups was 63,8 years. Mean serum PSA at diagnosis was of 8,8 ng/ml , a PSA significant difference was found between anterior and posterior tumours (p<0,001) and between anterior and symmetrical tumours(p=0,021) (12,0, 8,1 and 9,4 ng/ml respectively). 22,2% anterior tumours needed more than one biopsy session to be diagnosed while it only happened in 10,2% posterior tumours. A mean of 3,45 tumour-focus was found with no difference between groups. Anterior tumours presented a significantly greater MTD (p=0,038) than posterior tumours (2,72 vs. 2,26 cm respectively). Extraprostatic extension compromised different zones according to tumour location (Table 1). Stage distribution is shown in table 2. All pT4 cases had bladder neck affectation exclusively.
Salonia A.1, Zanni G.1, Scavini M.2, Freschi M.3, Montorsi F.1, Da Pozzo L.F.1, Scattoni V.1, Bertini R.1, Guazzoni G.1, Karakiewicz P.4, Rigatti P.1 1 Scientific Institute H. San Raffaele, Urology, Milan, Italy, 2Scientific Institute H. San Raffaele, Internal Medicine, Milan, Italy, 3Scientific Institute H. San Raffaele, Pathology, Milan, Italy, 4University of Montreal Health Center, Cancer Prognostics & Outcomes Research Unit, Montreal, Canada
INTRODUCTION & OBJECTIVES: To assess for presence of pathological grade shift in patients with prostate cancer (pCa) treated with RP over 20 years at the same academic institution. MATERIAL & METHODS: We reviewed all pathology records of n=4010 consecutive RP performed at our institution between 1984 and 2005. We abstracted patients’ age, date of surgery and Gleason score (GL). All cT1 to cT3 patients treated with RP also had a staging lymph node dissection. RESULTS: N=3925 records positive for adenocarcinoma were included in this analysis. Table 1 lists the pathological findings. Table 1 legend: a p<0.001 2001-2005 vs. 1991-1995 and 1996-2000; b p<0.006 vs. 1984-1990.
1984-1990
1991-1995
1996-2000
2001-2005
71
412
1023
2415
67.4 (12.1)
67.1 (9.2)
67.1 (9.5)
65.9 (9.9) a,b
GL<=6 (%)[95%CI]
57.4 [44.8, 69.3]
63.0 [58.1, 67.7]
61.8 [58.7, 64.9]
40.8 a,b[38.8, 42.8]
GL 7 [3+4] (%)
22.0 [12.9, 33.8]
15.3 [11.9, 19.2]
18.4 [16.0, 20.9]
29.3 a [27.4, 31.2]
GL 7 [4+3] (%)
7.4 [2.4, 16.3]
5.7 [3.6, 8.4]
10.2 [8.4, 12.3]
17.4 a [15.9, 19.0]
GL >=8 (%)
13.2 [6.2, 23.6]
16.0 [12.6, 20.0]
9.6 [7.8, 11.6]
12.5 [11.2, 13.9]
N Tab 1
Ant
Post
Sym
Apex
12(33,4)
31(30,1)
12(26,1)
Anterior
13(36,1)
2(1,9)
8(17,4)
Posterolateral
4(11,1)
67(65,1)
21(45,6)
B-N
7(19,4)
3(2,9)
5(10,9)
Tab 2
n(%)
Ant
Post
Sym
pT2a
n(%)
1(3,7)
11(8,1)
3(7,7)
pT2b
11(40,7)
56(41,2)
17(43,6)
pT3a
8(29,6)
52(38,2)
12(30,8)
pT3b
0 (0)
14(10,3)
2(5,1)
pT4
7(25,9)
3(2,2)
5(12,8)
CONCLUSIONS: PC with anterior location present a greater PSA at diagnosis, need more biopsies for diagnosis, have more tumour volume, and more bladder neck affectation than those with posterior or symmetrical tumour predominance. Using the urethra as longitudinal axis of reference is useful to classify prostate cancer as anterior, posterior or symmetrical.
Age in years [median (IQR)]
CONCLUSIONS: Our data confirm previously observed trends and indicate that grade at diagnosis shifted heavily toward pCa with moderate differentiation. Significantly reduced rates of welldifferentiated pCa are seen and the rates of poor prognosis disease are stable. Because assignment of GL score has been changing over time (namely, “the Will Rogers phenomenon”) and given that grade has an overwhelming impact on patient’s outcome, further studies are mandatory to evaluate whether a grade re-assignment could impact cancer control outcomes.
Eur Urol Suppl 2006;5(2):99