Study of prostatic pathology and its correlation with prostate specific antigen

Correspondence: Dr. Suspana Hirachand, MBBS,MD Department of Pathology Kathmandu Medical College and Teaching Hospital, Kathmandu, Nepal E-mail: suspi1974@hotmail.com Background: Diseases primarily inflicting prostate gland are inflammation, benign prostatic hyperplasia and cancer. Prostate specific antigen is a protein produced by the cells of prostate gland. It has been widely used in the diagnosis and management of patients with prostatic cancer. The aim this study was to determine the correlation between serum prostate specific antigen level and histological findings in biopsy specimens of men with prostatic disease.

obstruction. 1,2he incidence of prostatic lesions increases with increasing age.In the aging male, there is significant tissue remodeling taking place within the prostate.It was postulated that the growth is the result of a disturbed balance between apoptotic and proliferative activities with net reduction in apoptotic activity.Histologic analysis showed a decreased apoptotic activity in glandular and basal epithelial cells of the prostate.][5] Of the diseases which affects the prostate the most frequently encountered in clinical practice are benign prostatic hyperplasia, prostatic cancer and prostatitis. 6Prostate specific antigen (PSA), a glycoprotein serine protease, was first identified by Wang et al. in 1979. 7 Prostate specific antigen (PSA) is a widely used tumor marker for prostatic cancer. 8,9It is well known that PSA is prostatic specific, not a disease specific marker.PSA level can increase in nonmalignant conditions like benign prostatic hyperplasia, inflammation, diagnostic and surgical procedures.These conditions can mimic cancer and cause confusion in diagnosing especially in prostatic carcinoma where PSA is used as a screening test. 10nce, this study was undertaken to determine the correlation between serum PSA level and histological findings in biopsy specimens of men with prostatic disease.

MATERIALS AND METHODS
This is a prospective study carried out from October 2014-September 2016 ( 2 years) in the department of Pathology, Kathmandu Medical College and teaching Hospital, Kathmandu, Nepal.This study included 128 cases with prostatic lesions.PSA values of these cases were recorded before the surgical process.Serum PSA levels were estimated using chemiluminescent assay.Transurethral resection of prostate (TURP) biopsies were fixed in formalin (10%), processed and stained with Haematoxylin and Eosin for histopathological examination.Diagnostic criteria for benign prostatic hyperplasia (BPH), prostatitis, Prostatic intraepithelial neoplasia (PIN), and adenocarcinoma were adapted from guidelines laid down by World Health Organization (WHO) 2004.

RESULTS
The present study constituted a total of 128 cases, age ranged from 46 to 88 years (mean 68 years) diagnosed with benign (BPH and BPH with prostatitis), premalignant (LGPIN and HGPIN) and malignant (adenocarcinoma prostate) lesions of prostate.Maximum number of cases (n=47; 36.72%) were in the age group of 61-70 years followed by 71-80 years age group (n=43; 33.5%).Only 2 cases (1.56%) were observed younger than 50 years of age.
Out of 128 cases, 95 (74.22%) were of BPH followed by prostatic intraepithelial neoplasia, adenocarcinoma prostate and prostatitis.(Table1)Benign prostatic hyperplasia (BPH) was the most common histological lesion encountered (n=95; 74.22%) with maximum incidence seen in 61-70 age group (35 cases).(Table 1) Prostatic adenocarcinoma was seen a decade older than those with benign lesions.PSA values were classified into intervals of 7ng/ml.The number of lesions, when correlated with PSA, showed maximum number of cases (n=94; 73.43%) in PSA range of 0-7ng/ml.(Table 2) Maximum numbers of the benign cases (BPH and BPH with prostatitis) were seen in the PSA range of 0-7ng/ml.Most of the PIN lesions were seen within the PSA range of 0-7ng/ml and adenocarcinoma in the range of >20ng/ml.The results of comparison of serum PSA levels in benign and malignant lesions reveal positive correlation between the increase in   15,16 Benign prostatic hyperplasia was the most common histological lesion encountered (95 cases-74.22%) in our study with maximum incidence seventh decade, and this is in concordance with studies done by Lakhey M et al (65.33%),Josephine A et al(74.52%),and Vani BR et al (70.8%). 10,12,17 our study we found 10.16% of PIN lesions, similar as study done by Banerjee B et al (10%) and Maru AM et al (10.99%). 16,18In a study done by Shakya et al. they found only 1.88% of PIN lesions. 19The higher incidence of PIN lesions in our study may be due to the fact that most of the diagnosed lesions were in TURP specimens where the entire part of gland is sampled and examined under microscope thus allowing more chances of diagnosing PIN as it may occur in small foci within a gland, which might go unnoticed in a biopsy, hence limiting the usefulness of prostatic biopsy.
The incidence of prostatic adenocarcinoma was 10.16% in our study, which correlates with studies done by Banerjee B et al. and Wadgaonkar AR et al, where they reported 15% malignant cases in their studies. 16,20ostate specific antigen is secreted exclusively by prostatic epithelial cells.In several disease processes such as BPH, prostatitis, PIN and cancer, serum PSA level is increased.
From 30-50% of patients with benign prostatic hyperplasia have elevated serum PSA concentrations, depending on the size of the prostate and degree of obstruction, and in prostatic cancer the concentration is increased in 20-92% of patients, depending on the tumor volume.Measurement of the serum PSA is the most sensitive marker available for monitoring the progression of prostatic cancer. 21PSA is specific for prostatic tissue, but not specific for prostatic cancer.Umbehr MH et al. and Kiehl R et al. in their studies concluded that BPH and prostatitis is associated with high serum PSA, when glandular epithelium is disrupted. 22,23On the other hand, Papsidero LD et al. suggested that elevation of PSA is due to unknown substances released by epithelial cells in association with the inflammatory processes surrounding the affected area. 24In our study most of the patients with benign pathology had PSA in range of 0-7 ng/ ml (73.43%), while 26.57% had PSA level above 7 ng/ml owing to the probable fact as mentioned above.
In our study LGPIN and HGPIN were seen in 13 (10.16%)out of 128 cases.The PSA levels in 8cases (61.54%) were in range of 0-7 ng/ml, and in rest of the 5 cases PSA levels were > 7ng/ml.Prostatic adenocarcinoma were seen in 13 cases (10.16%) with PSA levels >20 ng/ml.Studies done by Lekili M et al., Kamleshwaran KK et al. and Banerjee B et al. also found the serum PSA levels >20ng/ml in prostatic adenocarcinoma. 16,25,26An increasing PSA levels implies underlying malignancy and more so of a high grade as evidence with significant relationship between PSA level and histopathology, especially when PSA level was more than 20 ng/ml.

CONCLUSION
In conclusion benign prostatic hyperplasia is the most common pathology encountered in prostatic specimens.PSA is specific for prostatic tissue and is raised in both benign and malignant lesions of prostate.But the chances of malignancy increases with rising value of PSA.

Table 2 : Correlation of PSA level and various prostatic lesions
PSA levels and malignant lesions.The rising PSA levels are associated with higher chances of malignant lesions.