Contributors

Original Article

PSA AND ITS CORRELATION WITH PROSTATIC DISEASE

1. Dr Sajjad Ahmed Baloch Assistant Professor Histopathology Gomal Medical College Dera Ismail Khan 2. Dr Balquis A Suleman Professor Of Histopathology Shaikh Zayed Hospital Lahore 3. Dr Muhammad Muzammil Tahir Assistant Professor Urology Shaikh Zayed Hospital Lahore 4. Dr Ghazi Khan Assistant Professor Urology Gomal Medical College Dera Ismail Khan

ABSTRACT Original Article

PROSTATIC SPECIFIC ANTIGEN (PSA) AND ITS CORRELATION WITH PROSTATIC DISEASE Sajjad Ahmed1, Bilques A Suleman2, Muhammad MuzammilTahir3, Ghazi Khan4
Among the Pathological processes effecting the prostate gland, prostatic carcinoma is the second leading cause of death. Approximately 50% of men with prostatic carcinoma have clinically advanced disease at the time of initial diagnosis. In 1979 tissue specific antigen was isolated from prostate using electrophoresis called PSA. Standard PSA reference ranges is 4ng/ml. Results below are considered normal, while high PSA level more likely is the possibility of carcinoma prostate.

AIMS AND OBJECTIVE Aim is to determine the morphological pattern of prostatic disease and its correlation with total serum prostatic antigen.

MATERIAL AND METHODS The study is conducted at Histology department in collaboration with urology department of Shaikh Zayed Hospital Lahore. 100 patients were enrolled in the study. Blood sample from the symptomatic patients of prostatic disease were

drawn. After receiving the tissue of prostate, either from core needle biopsies or TURP, tissue were processed for histopathology. RESULTS Average age of the patients suffering from benign prostatic hyperplasia was 62.34 6.6, while for carcinoma of prostate it is 64.73 8.8. Out of 100 patients, 70 patients have benign histology, while 30patients have carcinoma. Those having benign histology, 15 (21.4%) have PSA >10ng/ml, while only 20 (28.6%) have PSA less than 4ng/ml. Total 30 pt who were having Carcinoma of prostate, 15 patients have PSA range of more than 10ng/ml. 09 (30%) have PSA 4-10ng/ml, while 06 (20%) have PSA less than 4ng/ml.

Conclusion
In the normal range of PSA, There is high incidence of carcinoma prostate, so every patient having prostatic symptoms should undergo prostatic biopsy.

Key words;PSA, PROSTATE, CARCINOMA

Original article

PROSTATIC SPECIFIC ANTIGEN (PSA) AND ITS CORRELATION WITH PROSTATIC DISEASE
Sajad Ahmed1, Bilquis A Suleman2, Muhammad Muzammil Tahir3 Ghazi Khan
4

Mainly three pathological processes affect the prostate gland: (a) inflammation, which can be acute prostatitis, chronic prostatitis or granulomatous prostatitis; (b) benign prostatic hyperplasia (BPH); and (c) tumours. Benign prostatic hyperplasia is by far the most common pathological process affecting the prostate gland. There is no evidence that benign prostatic hyperplasia is a precursor of carcinoma. Prostate cancer is leading cause of death in America, second to lung cancer. In the European Union 13% of malignancies in men are prostate carcinoma and 8.6% of all carcinomas are due to this disease. It has become one of the leading male cancers in Asian countries as well 14. Prostate carcinoma is a significant cause of morbidity and mortality. It is the most common malignancy amongst men. The increased incidence of prostate carcinoma is in part related to the larger number of older men who are at risk of the disease. Apart from age other rare risk factors are family history, dietary factors, industrial pollution, hormones and others.

In 1979, a tissue specific antigen was isolated from prostate using gel electrophoresis and was called as PSA. A serologic test was developed allowing PSA to be measured in the serum. Prostate specific antigen is a glycoprotein produced primarily by the epithelial cells that line the acini and ducts of the prostate gland 15. The standard PSA reference range is 0-4 nanograms per milliliter [ng/ml. Results under 4 ng/ml are usually considered normal. A PSA level of 4 to 10 ng/ml is considered slightly elevated, levels between 10 and 20 ng/ml are considered moderately elevated; and anything above 20 is considered highly elevated. The higher the PSA level, the more likely is the possibility of carcinoma prostate. Because PSA is produced by the body and can be used to detect prostate disease, it is called a biological marker 1. The only methods to detect prostate diseases were the digital rectal examination (DRE) and the serum marker prostate acid phosphatase before serum PSA test was available 2. Because of PSA testing, 30-35% of patients with clinically significant prostate cancer can be diagnosed before the disease can be palpated in the prostate; in more than 90% of patients, prostate cancer can be diagnosed before symptoms occur 2

OBJECTIVES

The objective of this study was to determine the value of raised total serum PSA levels in the diagnosis of prostate diseases.

MATERIALS, METHODS

It is Crosssectional descriptive study, conducted in the Histopathology Department at Shaikh Zayed Hospital (Federal Postgraduate Medical Institute) in collaboration with Departments of Urology and National Health Research Complex Lahore. This study included one hundred patients with prostatic diseases.

Male patients aged 40 years or above. Patients with symptomatic prostatic disease attending the Department of Urology. Patients with abnormal digital rectal examination indicating hard or nodular prostate and undergoing needle prostatic biopsies, transurethral prostatic resection chips, as well as suprapubic prostatectomy specimens were included in this study. While Patients having ejaculated 2 days prior to having a PSA test as this can raise serum PSA levels. Patients on medication for BPH, baldness and herbal supplements, because they would most likely lower PSA levels. Patients having DRE before blood sample was taken.were excluded from study.Hundred patients qualifying the inclusion criteria were enrolled for the study. Consent was taken for PSA analysis (ELISA kit Neteria, UK) in National Health Research Complex and hence blood samples were drawn.

A designed proforma was filled and data thus collected was statistically
analyzed .All prostate specimens was properly preserved in fixative solution

(10% buffered) neutral formalin or with 95% methanol in properly labeled containers indicating the patients name, age and medical record number. In the laboratory the specimen was examined grossly to observe the various macroscopic features. Core needle biopsies was embedded totally. TURP specimens was partially or totally submitted according to the number of chips. Representative sections was taken from the total prostectomy specimens. Tissue taken from the specimen was processed and paraffin embedded tissue blocks were made as per standard techniques. Multiple sections with thickness range 3 -5micrometer,stained with Haematoxylin and Eosin was made and examined microscopically. All prostatic lesions was categorized into benign and malignant, Malignant lesions was kept as one category including cases of prostatic

adenocarcinoma. The histological findings was recorded in proforma.

RESULTS

A total of 100 prostatic disease patients were included in the study. The average age of the patients was 63.067.35 (95% CI; 61.6 to 64.5) years. Out of 100 subjects, the prostate cancer (Ca) cases were 30% and benign prostate hyperplasia (BPH) were 70% .Mean comparison of age, TPSA (total prostatic specific antigen) between benign prostatic hyperplasia and prostate cancer was calculated. Age was not statistically significant between benign prostatic hyperplasia and prostate cancer (t-value = -0.154, P=0.13). Mean PSA was found to be highest in Ca cases (25.721.6 ng/ml) and lower in the BPH cases (12.76.9 ng/ml) it shows that significant difference was found in mean PSA

between BPH and Ca patients (t-test apply; p<0.01). This proved that there is highly significant increase in PSA level in cases of prostatic carcinoma (Table 1). The various cutoff ranges for serum PSA were established <4 ng/mL, 4-10 ng/mL (gray zone) and >10 ng/mL. At less than 4 ng/mL, 20 cases (28.6%) were BPH and 6 cases (20%) were carcinoma prostate. In the range of 4-10 ng/mL (gray zone), 35 cases (50%) were BPH and 9 cases (30%) were prostatic carcinoma. In the higher values of >10 ng/mL, the incidence of carcinoma of prostate was highest being 15 cases (50%) out of 30 prostatic cancer patients and 15 cases (21.9%) out of 70 cases of BPH (Table 2).

Table 1 Mean comparison of two characteristics between benign prostatic hyperplasia and prostate cancer (Age and TPSA)

Variables Age (Years) TPSA

BPH 62.346.6

Ca 64.738.8

T-test -0.154

P value 0.13

12.76.9 (ng/ml)

25.721.6

-4.6

P<0.01*

*Statistical significant Key: TPSA = Total prostate specific antigen (ng/ml) BPH = Benign prostate hyperplasia Ca = Prostate cancer

Table 2 Outcome of total prostate specific antigen against gold standard (histology)

Histology TPSA BPH 15 (21.4%) 35 (50%) 20 (28.6%) 70 Ca 15 ( 50%) 09 (30%) 06 (20%) 30 TOTAL

>10 ng/mL 4 10 ng/mL < 4 ng/mL Total

30 (71.4%) 44 (80%) 26 (48.6%) 100

Key: BPH = Benign prostatic hyperplasia Ca = Prostate cancer TPSA = Total prostate specific antigen

DISCUSSION
Early diagnosis of prostate cancer is an important issue among urologists and pathologists as it is second leading cause of death in men. For the early detection of cancer various methods have been used. DRE is one of the oldest and relatively least invasive technique, but it fails to detect many cases of cancer in their early stages. Various studies carried out in western countries showed that DRE detected Ca-prostate in the range of 0.1 to 1.7% 3 TRUS may also facilitate

the detection of Ca-prostate. Among such procedures PSA has emerged as a very useful marker of Ca-prostate and for monitoring effects of therapy 6. Prostate specific antigen is used as a tumour marker for the diagnosis of prostate cancer. However, men with BPH and prostatitis also have elevated PSA levels in most cases, leading to a large percentage of false positive screening results.7 The present study was conducted to evaluate the utility of PSA measurements for the early detection of prostate diseases and to establish a correlation between the histopathological diagnosis of BPH, Ca-prostate and total serum PSA levels in local population. The table 1 shows the mean TPSA was 12.76.9ng/ml for BPH and 25.721.6ng/ml for ca-prostate cases (p value<0.01 significant). The mean PSA level in Ca-prostate cases was higher than BPH subjects, which is a significant increase. The same results are reported by Stamey et al (1987), who showed that serum PSA is elevated in Ca-prostate cases. These elevations occur as a result of disruption of the normal prostatic architecture that allows PSA to diffuse into the prostatic tissue and gain access to the circulation. The mean PSA in Caprostate cases also increases with age. According to our study, the PSA value in 20% of cases of ca-prostate was <4ng/ml (Table 2). In another study conducted by Thompson et al (2004) concluded almost the same percentage (15%) of Ca-prostate cases with PSA value <4ng/ml.

In our study the cutoff ranges for serum PSA were taken as 0-4 ng/ml, 410 ng/ml and >10 ng/ml. Different workers have reported different ranges of serum PSA for the diagnostic gray zone, for instance, Dalva et al (1999) used a cutoff of 4.1-10 ng/mL, Ortega et al (2000) used 2.5-10 ng/mL. Since the maximum overlap between the serum PSA values of BPH and carcinoma prostate cases was investigated in the range 4.1-20 ng/mL, that was taken as the gray zone. This was in accordance with the work of Ohuchi et al (2000) and Gaspar et al (2000). Our results are also in accordance with the results of Carter et al (1992) and Oesterling et al (1992), who reported that the values above the normal range (0-4 ng/ml) are one of the earliest signs of prostate diseases, in many cases allowing diagnosis while the cancer is still confined to the gland. In another study Catalona et al (1993), reported that the levels of TPSA of 4.0 ng/mL or higher are strong indicators of the possibility of prostate cancer. The results of TPSA test for Ca-prostate cases were compared with those of BPH cases performed in the present study. Total prostatic specific antigen in BPH cases was 71.4%, while in carcinoma prostate cases was 80% (Table 2). These results were in conformity with the results of Catalona et al (1998), who reported that 65% of patients with an elevated PSA concentration are affected by a non-malignant disease such as BPH. In upto 4-10 ng/ml PSA concentration, BPH was predominant contributor (50%). In the cutoff >10 ng/ml Ca prostate was dominant (50%). It is possible that the PSA values for BPH are intermediate between the Ca-prostate values and normal values. Thus we have defined the

cutoff values for the three stages of prostate conditions (normal, BPH and Caprostate). But we also suggest that other factors like patients age, clinical findings as well as total PSA should be considered while making the diagnosis.

Conclusion:
As there is high incidence of Carcinoma prostate in those patients having normal range of PSA level, so every patients may undergo prostatic biopsy

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