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- Original Article -
Mass screening of prostate cancer in a Chinese population:
the relationship between pathological features of prostate
cancer and serum prostate specific antigen
Hong-Wen Gao1,3, Yu-Lin
Li2, Shan Wu2, Yi-Shu
Wang2, Hai-Feng Zhang3, Yu-Zhuo
Pan3, Ling Zhang3, Hiroo
Tateno4, Ikuro Sato4, Masaaki
Kuwahara5, Xue-Jian Zhao3
1Department of Pathology, Jilin University Second Hospital, Changchun 130041, China
2Department of Pathology, Basic Medical College, Jilin University, Changchun 130021, China
3Prostate Diseases Prevention and Treatment Research Center, Jilin University, Changchun 130021, China
4Department of Pathology, Miyagi Cancer Center, Miyagi Prefecture, Japan
5Department of Urology, Miyagi Cancer Center, Miyagi Prefecture, Japan
Abstract
Aim: To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in a
Chinese cohort and their association with serum prostate specific antigen (PSA).
Methods: A total of 12 027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen (tPSA) test (by
Elisa assay). Transrectal ultrasound-guided systematic six-sextant biopsies were performed on those whose serum tPSA
value was >4.0 ng/mL and those who had obstructive symptoms (despite their tPSA value) and were subject to
subsequent pathological analysis with the aid of the statistic software SPSS 10.0 (SPSS. Inc., Chicago. USA). Results: Of the 12 027 cases, 158 (including 137 patients whose serum tPSA values were >4.0 ng/mL and 21 patients [serum tPSA
<4.0 ng/mL] who had obstructive symptoms) undertook prostate biopsy. Of the 158 biopsies, 41 cases of prostatic
carcinoma were found (25.9 %, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma
accounted for 61 % and 34 %, respectively. A significant linear positive correlation between the serum tPSA and the Gleason
scores in the 41 cases of prostatic carcinoma
(r = 0.312, P < 0.01) was established. A significant linear positive correlation
between the serum tPSA value of the 41 prostatic carcinoma and the positive counts of carcinoma in sextant biopsies was
established (r = 0.406, P < 0.01), indicating a significant linear relationship between serum tPSA and the size of tumor. Conclusion: This study was the first to conduct mass screening for prostate cancer by testing for serum tPSA values and
the first to investigate the pathological features of prostate cancer in a cohort of Chinese men. Our results reveal that the
moderately differentiated carcinoma is the most common type of prostate cancer. This study also has shown that the
serum tPSA value in prostate cancer is associated with the Gleason score and the size of
tumor. (Asian J Androl 2005 Jun; 7: 159_163)
Keywords: prostate cancer; mass screening; prostate specific antigen; pathomorphology
Correspondence to: Prof. Xue-Jian Zhao, Prostate Diseases Prevention and Treatment Research Center, Jilin University, Changchun 130021, China.
Tel/Fax: +86-431-563-2348
E-mail: pro_2@jlu.edu.cn
Received 2004-02-24 Accepted 2004-12-06
DOI: 10.1111/j.1745-7262.2005.00029.x
1 Introduction
Traditionally, it has been thought that the incidence
of prostate cancer in China and Japan is low; however,
in these countries, the incidental discovery of prostate
carcinoma in autopsies is not uncommon.
Because of the lack of specific clinical symptoms
found at the early stages of prostate cancer, in more
than half of the cases in China, the disease is not
detected until it has reached stage D with metastases.
Therefore, mass screening using serum total prostate
specific antigen (tPSA) has been adopted as the
paramount approach for early detection of prostatic
carcinoma. It is recommended that the positive serum
tPSA candidates, whose serum tPSA value is > 4.0
ng/mL, should be subject to transrectal ultrasound-guided
six-sextant prostate needle-biopsy [1].
Pathological studies on mass screening for prostate cancer demonstrated
that in Japan the occurrence of well differentiated and
poorly differentiated carcinomas is high [2]; whereas in
the USA, moderately differentiated carcinomas are
predominant [2, 3]. However, the pathological features of
mass screening for prostate cancer in China have not yet
been investigated.
The purpose of the present study was to investigate
the pathological features of the 158 prostate biopsies
through mass screening for prostate cancer in the
Chinese population of Changchun and their association with
serum PSA.
2 Materials and methods
2.1 Serum tPSA assay
From July 1999 to April 2002, a total of 19 808
Chinese men in Changchun who were > 50 years old were
invited for screening. A total of 12 027 men agreed to
participate with a refuge rate of 38.28 %. The serum
tPSA level was determined using the Elisa assay kit
(CanAGDiagnostics, Gothenburg, Sweden).
2.2 Biopsy and immunohistochemistry
Transrectal ultrasound-guided systematic six-sextant
biopsies were performed on those whose serum tPSA value were >4.0 ng/mL and those who had obstructive
symptoms despite their tPSA value. All specimens were
routinely fixed in 10 % neutral buffered formalin and
embedded in paraffin. Sections cut into
4 ¦Ìm were deparaffinized in xylene, rehydrated in graded alcohols and
stained with hematoxylin and eosin.
Immunohistochemical staining of 16 cases of a typical small acinar
proliferation was performed with the avidin-biotin-peroxidase
complex method using the monoclonal antibodies against
PSA and keratin34bE12 (Dakopatts, Hamburg, Germany).
2.3 Patho-morphological analysis
The Gleason grading system was used for grading
prostatic adenocarcinomas; the latter were divided into
five grades and nine scores (2_10) [4]. The prostatic
adenocarcinomas were divided into three groups: 1)
well-differentiated (Gleason scores in the range of 2_4), 2)
moderately-differentiated (Gleason scores in the range
of 5_7), and 3) poorly-differentiated (Gleason scores in
the range of 8_10).
2.4 Prostate intraepithelial neoplasia
Prostate intraepithelial neoplasia (PIN) was divided
into low-grade and high-grade. The high-grade PIN is
characterized by the proliferation of highly atypical cells
having more uniformly enlarged nuclei than low-grade
PIN. Prominent nucleoli are present in many of the cells.
2.5 Statistical analysis
An analysis of frequencies, explore, crosstab and
correlation was performed using SPSS software 10.0
(SPSS, Chicago, USA). The Correlation analysis was
performed with the Pearson and Spearman method.
3 Results
In this study, 12 027 cases of mass screening for
prostate cancer (by serum tPSA tests) were performed:
11 214 men whose serum tPSA values were <
4.0 ng/mL accounted for 93.2 % of the total and 813 men whose
serum tPSA were > 4.0 ng/mL accounted for 6.8 %.
One hundred and fifty-eight patients were subject to
prostate biopsies according to the serum tPSA value and
clinical manifestation. Of the 158 cases, 137 had a high
serum tPSA level >4.0 ng/mL. Of the 137 patients, the
serum tPSA value in 82 was 4_10 ng/mL, in 31 cases
10_20 ng/mL and in 24 cases > 20.0 ng/mL. Of the
12 027 men screened, there were 202 candidates who
presented because of obstructive outlet symptoms and
21 patients (whose serum tPSA value was later found to
be < 4.0 ng/mL) who were biopsied because they had an
abnormal digital rectal examination.
There were 96 cases of benign prostate hyperplasia
(BPH) (60.8 %, 96/158), 41 cases of prostate carcinoma
(Pca) (25.9 %, 41/158), seven cases of PIN (4.4 %),
six cases of atypical glands (3.8 %), two cases of
suspicious cancer (Sca) (1.3 %) and six cases of
granulomatous prostatitis (3.8 %). The diagnosis of atypical glands
and suspicious cancer was made according to the immunochemical staining.
The age and serum tPSA levels of the 12 027
participants and the 158 men who underwent biopsies are shown
in Table 1. The detection rate of prostate cancer (Pca)
in the different age ranges of the screening cohort of
12027 Chinese men is shown in Table 2. The two tables
show that a significant linear positive correlation exists
between the serum tPSA and ages (r = 0.458,
P < 0.01) and between the detection rate of Pca and age
(r = 0.205, P < 0.05).
In this study, Gleason grade 1 carcinoma was not
observed. Gleason grade 2 carcinoma was seen in nine
biopsy sections of the 158 cases. Gleason grade 3
carcinoma was seen in 30 sections, Gleason grade 4
carcinoma in 25 sections and Gleason grade 5 carcinoma in
eight sections. The results from this study show that the
distribution of patients was 4.9 %, 17.1 %, 22.0 %,
22.0 %, 17.1 %, 17.1 % and 0 % in Gleason scores 4,
5, 6, 7, 8, 9 and 10, respectively.
Special types of prostatic carcinoma were diagnosed,
including one case of ductal carcinoma (endometrioid
carcinoma) and three cases of signet ring cell carcinoma.
Perineural infiltration and adenocarcinoma with glomeruliod structure were seen in three sections and
one section, respectively.
There were five cases of low-grade PIN in the 158
prostate biopsies and two cases of high-grade PIN
presented in the biopsies.
There were 16 cases that were diagnosed as atypical
small acinar proliferations of uncertain significance
(ASAPUS) in 158 biopsies [5]. It has been recognized
that immunohistochemical staining against 34bE12 has
been a useful approach to the discrimination between
benign and malignant glands. In this study, the
immunohistochemical staining result revealed eight cases of small
acinar carcinoma due to the absence of the basal cell
layer, two cases of suspicious cancer due to the
disruption of the basal cell layers and six cases of atypical glands
with normal basal cell layer.
As Figure 1 shows, the incidence of
poorly-differentiated adenocarcinoma, and moderately-differentiated
adenocarcinoma, was markedly higher than that of
well-differentiated prostatic adenocarcinoma.
A correlation analysis between the serum tPSA and
Gleason scores and positive counts of carcinoma in the
41 cases of prostatic adenocarcinoma is shown in
Figures 2 and 3. As Figure 2 shows, a significant linear
positive correlation exists between the serum tPSA and
the Gleason scores (r = 0.312,
P < 0.01) and a significant linear positive correlation also exists between the
serum tPSA value of the 41 cases of prostatic
adenocarcinoma and the positive counts of carcinoma in sextant
biopsies (r = 0.406, P < 0.01; Figure 3).
4 Discussion
The present study is the first in China to conduct a
mass screening of more than 10 000 men for prostate
cancer by testing the serum tPSA value of participants.
The detection rate of prostate cancer is influenced by
the number of biopsy cores available for study; as
compared with the standard sextant biopsy method,
increasing core numbers to 12_14 can enhance the detection
rate significantly. Currently, however, sextant biopsy is
still the standard biopsy technique for mass screening
for prostate cancer. In the present study, 158 suspicious
cases that had undergone transrectal ultrasound-guided
systematic six-sextant biopsy were subject to
pathological examination and patho-morphological analysis.
This study showed that the tPSA value was increased
with age (r = 0.458, P < 0.01), and also showed that the
detection rate of prostate cancer was increased with age
(r = 0.205, P < 0.05). In addition, the serum tPSA value
in cases of Pca was higher than that in BPH, PIN and
prostatitis. Although our results showed that the mean
age of Pca patients was older than that of BPH, PIN and
prostatitis patients, this difference was not significant.
We believe that this may attribute to the small numbers
of biopsies.
In this study, 41 cases of prostatic adenocarcinoma
were found in 158 prostatic biopsies. Our results have
demonstrated that the moderately differentiated carcinoma
is the most common type of prostate cancer accounting
for 61.4 %, although the poorly differentiated carcinoma
is also frequently found. This is somehow similar to the
pathological features of prostate cancer in the American
population characterized by the high incidence of
moderately differentiated carcinoma [3]. However, Harada
et al. reported that in Japan the occurrence of
well-differentiated (Gleason 2_4 score) and poorly differentiated
(Gleason 9_10 score) carcinoma are high
[2]. Furthermore, in a cohort of Jamaican men, 60 % of Pca
had a Gleason score of 8_10, which indicates that the
poorly differentiated carcinoma is the most common type
of prostate cancer [6].
The serum tPSA concentration is extremely important in detecting early prostate cancer. Catalona
et al.[7] reported that the incidence of prostate cancer was
2.2 % in men whose tPSA level was greater than
4.0 ng/mL. The positive predictive value for a tPSA level
between 4.1 ng/mL and 10.0 ng/mL was 22.4 %_26.5 %
and for a tPSA level above 10.0 ng/mL was 50 %_67 %
[7]. In this study, 41 prostatic carcinomas were found
and account for 25.9 % of the biopsies. Two cases out
of 21 (9.5 %) with a serum tPSA value <4.0 ng/mL had
carcinoma detected and in the 81 biopsies where the
serum tPSA value was at the range from 4.1 ng/mL to
10.0 ng/mL, 12 cases of prostatic carcinoma were
diagnosed accounting for 14.8 % (12/81). In the 31 biopsies
with a serum tPSA value of 10.1 ng/mL to 20.0 ng/mL,
eight prostatic carcinomas were identified accounting for
29.0 % (8/31). Of the 24 biopsies with serum tPSA
values above 20 ng/mL, 19 prostatic carcinoma were
diagnosed, accounting for 79.0 % (19/24). Our results
also reveal that detecting the rate of prostate cancer in
biopsy increases with the elevation of serum tPSA levels
(r = 0.428, P < 0.001). This is consistent with the
findings of Catalona et al. [7].
Emerging evidence has demonstrated that the serum
tPSA level is relevant to the Gleason's grading in
prostate cancer. In the present study, a linear positive
correlation between serum tPSA value and histological
grading could be seen. Several studies have shown a direct
relationship between serum tPSA levels and estimated
prostatic volume [8], while the results from this study
have shown that there is a significant linear positive
correlation between the serum tPSA value and the positive
counts of carcinoma in the sextant prostatic biopsies,
thereby indicating an association between the positive
counts of carcinoma and the volume of tumors.
In conclusion, this study was the first to conduct
mass screening for prostate cancer and to investigate
the pathological features of prostate cancer in a cohort
of Chinese men. Our results reveal that the moderately
differentiated carcinoma is the most common type of
prostate cancer. This study also has shown that serum
tPSA value is associated with the pathological grading.
Acknowledgement
This study was kindly supported by a research fund
from Japan International Cooperation Agency (JICA). We
would like to thank Professor Xing-Yi Zhang in the De
partment of Thoracic and Cardiovascular Surgery in the
Second Hospital of Jilin University for his assistance in
writing and preparing this manuscript.
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