Prognostic importance of prostate
specific antigen in assessing histological grade of prostatic
adenocarcinoma
Shanthi V1, Vydehi BV2,
Bhavana G3, Swathi S4, Shehnawaz B5, Dahlia J6
1Dr Vissa Shanthi, Associate professor, 2Dr Venkata Vydehi
Bheemaraju, Professor, 3Dr Bhavana Grandhi,
Assistant Professor, 4Dr Swathi Sreesailam, Assistant Professor, 5Dr Bhat Shehnawaz Tutor, 6Dr Dahlia
Joseph, Tutor. All are affiliated to Department of Pathology, Narayana
Medical College and Hospital, Nellore, Andhrapradesh, India
Address for
correspondence: Dr Vissa Shanthi, Email:
santhijp@gmail.com
Abstract
Background:
Prostatic adenocarcinoma is one of the most common cancer occurring in
the men above 50 years of age. Prostate specific antigen (PSA) is an
important serum marker which helps in the diagnosis of prostatic
adenocarcinoma and also aids in estimating the tumor grade. Objective:
To evaluate the correlation between serum PSA levels and
Gleason’s histological grade of prostatic adenocarcinoma. Methods: A
retrospective study analysis was done for 128 patients whose
transrectal ultrasonography (TRUS) guided prostate biopsy were studied
in our hospital. The serum PSA levels were noted and compared with
different Gleason histological grading in adenocarcinoma patients. Results: Our study
included 128 cases, out of which 86 cases were benign and 42 cases were
malignant. Maximum numbers of benign and malignant lesions were in the
age group of 60 – 69 years. Most of the malignant cases
(80.95%) had PSA level above 20ng/ml. Histological grade III carcinomas
were restricted to PSA levels of 50ng/ml and above, while grade I was
restricted to PSA level of less than 10ng/ml and grade II carcinomas
did not have any correlation with specific PSA levels. Conclusion: Our
study showed that there was significant correlation between serum PSA
value and Gleasons histological grade of prostatic adenocarcinoma.
Key words:
Prostate Specific Antigen, Gleason Histological Grade, Adenocarcinoma
Manuscript received:
2nd Feb 2015, Reviewed: 17th
Feb 2015
Author Corrected: 11th
Mar 2015, Accepted for
Publication: 29th Mar 2015
Introduction
Prostate specific antigen (PSA) is a glycoprotein enzyme secreted by
epithelial cells of the prostate. PSA is a member of the kallikrein
related peptidase family which is an important tumor marker in the
diagnosis of prostatic adenocarcinoma. PSA is present in serum of men,
with normal prostate, but the levels are elevated in pathological
conditions like prostatitis, hyperplasia and prostatic carcinoma [1].
PSA is produced by normal epithelial cells lining the prostatic glands,
hyperplastic epithelial cells and pleomorphic epithelial cells in the
prostatic adenocarcinoma. In conditions like inflammation, hyperplasia
and malignancy, there is destruction of cell integrity which leads to
release of PSA into circulation. This produces increase in serum PSA
level [2].
In prostatic adenocarcinoma, the malignant cells produce less PSA then
healthy epithelial cells. But as there is great increase in number of
cells in carcinoma, the PSA produced is more and serum levels are
raised. The malignant cells in most of the prostatic carcinoma are
immunopositive for PSA and have been used for identifying the
metastatic deposits.
In protatic carcinomas, serum PSA value depends upon the
differentiation of the tumor cells. The poorly differentiated prostatic
tumors will have low serum PSA levels when compared to well
differentiated tumors. A pretreatment serum PSA level not only predicts
the grade of prostatic adenocarcinoma but also acts as an independent
predictor of response to therapy [3].
Material
and methods
This is retrospective study performed at Narayana Medical college and
hospital in Nellore during the period of Jan 2012 to Jan 2015. This
study included 128 patients, in whom transrectal ultrasonography (TRUS)
guided prostatic biopsy were taken and sent for histopathological
examination. Minimum of ten core biopsies were taken from apex, middle
region, right and left sides of base of the protate and also from the
nodule if present. Biopsy was performed under ultrasound guidance using
18- gauge, Tru cut core biopsy needle which is 20 cm long. The specimen
was sent in formalin to pathology department where they were examined
for the presence of carcinoma. Preoperative serum PSA levels are noted
in these cases. The prostatic biopsies which did not show malignancies
were excluded and biopsies which showed malignancies were studied. PSA
levels in these cases were compared with the Gleasons grade of these
tumors.
Results
and Observation
Prostatic biopsy specimens obtained from 128 patients who attended
urology department in Narayana Medical College and Hospital were
studied for the period of January 2012 to January 2015. Out of 128
prostatic biopsy specimens 86 were diagnosed as benign and 42 were
diagnosed as malignancy. These cases were studied in relation to age
and serum PSA levels. In malignant cases serum PSA levels were compared
with grades of carcinoma.
Table 1: Prostatic
lesions in relation to different age groups
|
Age
group
|
Total
number of cases
|
Benign
cases
|
Malignant
cases
|
|
30 – 39yrs
|
1 (0.78%)
|
0
|
1 (2.38%)
|
|
40 – 49yrs
|
4 (3.13%)
|
4 (4.65%)
|
0
|
|
50 – 59yrs
|
28 (21.87%)
|
16 (18.60%)
|
12 (28.57%)
|
|
60 – 69yrs
|
52 (40.62%)
|
37 (43.02%)
|
15 (35.71%)
|
|
70 – 79yrs
|
37 (28.91%)
|
28 (32.56%)
|
9 (21.43%)
|
|
80 – 89 yrs
|
5 (3.91%)
|
1 (1.16%)
|
4 (9.52%)
|
|
90 – 99 yrs
|
1 (0.78%)
|
0
|
1 (2.38%)
|
|
Total
|
128
|
86
|
42
|
Prostatic biopsies in relation to age were studied by dividing them
into 7 groups (Table 1). Maximum numbers of benign and malignant cases
were in the group of 60 -69 years.
Table 2: Correlation of
PSA levels with Prostate biopsy
|
PSA
range (ng/ml)
|
Total
number of cases
|
Benign
cases
|
Malignant
cases
|
|
0.01 – 3.99
|
0
|
0
|
0
|
|
4.00 – 9.99
|
22 (17.19%)
|
20 (23.26%)
|
2 (4.76%)
|
|
10.0 – 19.99
|
40 (31.25%)
|
34 (39.53%)
|
6 (14.29%)
|
|
20.0 – 49.99
|
29 (22.66%)
|
23 (26.74%)
|
6 (14.29%)
|
|
50.0 – 99.99
|
20 (15.63%)
|
6 (6.98%)
|
14 (33.33%)
|
|
100.0 – 149.99
|
12 (9.37%)
|
3 (3.49%)
|
9 (21.43%)
|
|
150.0 – 199.99
|
0
|
0
|
0
|
|
>200
|
5 (3.9%)
|
0
|
5 (11.9%)
|
|
Total
|
128
|
86
|
42
|
PSA levels in all the cases were studied (Table 2). In our study no
case was found to have PSA levels less than 4ng/ml. 22 cases had PSA
levels in the range of 4.0 – 9.99 ng/ml. Out of these 20
cases were benign and 2 cases were malignant. In the PSA range of 10
– 19.99 ng/ml, 40 cases were noted, out of which 34 were
benign and 5 were malignant. 29 cases had PSA values in the range of 20
– 49.99 ng/ml, out of which 23 were benign and 6 cases were
malignant. In the range of 50 – 99.99 ng/ml, 20 cases were
noted, out of which 6 cases were benign and 14 cases were malignant. 12
cases had PSA values in the range of 100-149.99 ng/ml, out of which 3
cases were benign and 9 cases were malignant. There were 5 cases which
had PSA values of more than 200 and all were malignant.
Table 3: Correlation
between serum PSA levels and Gleason grade of prostatic adenocarcinoma
|
PSA
range (ng/ml)
|
Grade
1
|
Grade
2
|
Grade
3
|
|
4 – 9.99
|
2 (4.76%)
|
0
|
0
|
|
10.0 – 19.99
|
0
|
5 (11.9%)
|
0
|
|
20 – 49.99
|
0
|
7 (16.67%)
|
0
|
|
50 – 99.99
|
0
|
10 (23.8%)
|
4 (9.52%)
|
|
100 – 149.99
|
0
|
7 (16.67%)
|
2 (4.76%)
|
|
150 – 199.99
|
0
|
0
|
0
|
|
Ø 200
|
|
5 (11.9%)
|
|
|
TOTAL
(n=42)
|
2
(4.72%)
|
34
(80.95%)
|
6
(14.29%)
|
PSA levels in prostatic carcinomas were compared with
Gleason’s grade of the tumor (Table 3). Maximum numbers of
prostatic adenocarcinomas were in grade 2 [34 cases (80.95%)]. Maximum
cases in grade 2 and grade 3 had PSA range of 50 – 99.99
ng/ml. 2 cases of grade 3 adenocarcinoma were in the PSA range of 100
– 149.99 ng/ml and 2 cases of grade 2 adenocarcinoma had PSA
range of 4 – 9.99 ng/ml.
In our study there was a good correlation of rising PSA with grade upto
PSA level of 50. Beyond that PSA level, there was no significant
correlation in between the PSA level and Gleasons grade.
Discussion
Prostatic carcinoma is the most common malignancy among men and is
responsible for 10% of cancer deaths [4]. Prostatic carcinoma is second
to lung cancer as a leading cause of cancer related deaths in men.
Hormonal factors play a role in the development of prostatic carcinoma.
Incidence of prostatic carcinoma is low in patients with
hyperestrogenism resulting from liver cirrhosis and does not occur in
eunuchs castrated before puberty. Occupational exposure, smoking,
venereal diseases, sexual habits and diet do not show any demonstrable
correlation with prostatic carcinoma [5].
Almost 75% of the men diagnosed with prostatic cancer are age 65 or
older and the frequency increases with age. Clinical stage,
Gleason’s score and serum PSA are independent prognostic
factors in prostatic carcinoma and help to choose a definitive
treatment in carcinoma [6].
The U.S. Food and Drug Administration [FDA] in the United States has
approved that the annual screening of the prostatic cancer in men of
age 50 and older is by assessing serum PSA levels. If the PSA levels
are between 4 to 10 ng/ml, then it is considered to be suspicious and a
repeat PSA test is performed. Finally prostate biopsy should be taken
for histopathological analysis, if indicated [7].
PSA also known as Seminin, Kallikrein III, Semenogelase, P-30 antigen
and γ – Semino protein is a serine protease enzyme,
which has its gene located on the 19th chromosome. It is a 34KD
glycoprotein produced by epithelial cells of prostate [8]. Papsidero in
1980 first quantitatively measured PSA in blood and its clinical use as
marker of prostatic cancer was studied by Stamey [9].
In the blood normally PSA is present at very low levels of less than
4ng/ml. Increase in the serum PSA levels indicate prostatic cancer. PSA
levels can also be increased in benign prostatic hyperplasia,
prostatitis, irritation, and recent ejaculation [10, 11]. PSA levels
can also be raised on digital rectal examination [12].
In the blood only a small amount of PSA is available freely and large
amount of it is bound to the serum proteins. The ratio of free PSA to
total PSA will be reduced in Prostatic carcinoma. If the ratio is less
than 25% the risk of prostatic cancer increases. In men whose PSA
levels are between 4 to 10 ng/ml, the ratio of free to total PSA levels
helps in avoiding unnecessary biopsies [13].
Along with measuring the free to total PSA, the measurement of
proteolytic activity of the enzyme can improve the diagnostic value of
the test. The proteolytically active PSA has anti-angiogenic effect and
the presence of inactive proenzyme forms of PSA indicates presence of
disease [14].
Table 4: Correlation
between our study and other study in relation to PSA levels and
malignancy
|
PSA
levels (ng/ml)
|
Our
study (2012-2015)
|
Sladana
Zivkovic (2004)
|
|
0.01 – 3.99
|
0
|
1 (2.5%)
|
|
4 – 9.99
|
2 (4.76%)
|
11 (27.5%)
|
|
10 – 99.99
|
6 (14.29%)
|
7 (17.5%)
|
|
Ø 20
|
34 (80.95%)
|
21 (52.25%)
|
In the present study we evaluated the prognostic importance of
preoperative total serum PSA levels with grades of adenocarcinoma of
prostate. In our study maximum number of malignancies has serum PSA
value of more than 20ng/ml which coincided with study done by Sladana
Zivkovic (2004) who got 21 cases (52.5%) having PSA values above 20
ng/ml [15] (Table -4).
In our study no maliganancy was detected with PSA values in the range
of 0 – 3.99 ng/ml. In our study histological grade III
carcinomas were restricted to PSA levels of 50 and above, while grade I
was restricted to PSA level of less than 10ng/ml and grade II
carcinomas did not have any correlation with specific PSA levels.
In studies done by Lennox Anderson Jackson et al (2012), histological
grade III adenocarcinoma had a PSA range of 76 to 190 ng/ml, while
grade II carcinomas had PSA range of 20-100 ng/ml . Our study coincided
with the conclusion drawn from the studies of Lennox Anderson Jackson
et al (2012) that histologically higher grades of prostatic carcinomas
are associated with higher PSA levels [16].
Conclusion
With increasing PSA levels the possibility of malignancy is more,
although malignancies were seen at low PSA levels also. More over
positive relation was seen between higher levels of PSA and Gleasons
grade. But as the tumor becomes more poorly differentiated it may not
correlate with PSA levels because the tumor cells may not produce PSA
as they have lost differentiation.
Funding:
Nil, Conflict of
interest: None initiated.
Permission from IRB:
Yes
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How to cite this article?
Shanthi V, Vydehi BV, Bhavana G, Swathi S, Shehnawaz B, Dahlia J.
Prognostic importance of prostate specific antigen in assessing
histological grade of prostatic adenocarcinoma. Int J Med Res Rev
2015;3(3):268-272. doi: 10.17511/ijmrr.2015.i3.049.