PSA and diagnosis of Prostate cancer

Prostate-specific antigen (PSA) is now recognized as the premier tumor marker for prostatic cancer. Wang et.al reported PSA in the prostate in 1977 and characterized the protein definitively in 1979. PSA was purified from both prostatic tissue and seminal plasma. However, the interest of clinicians and pathologist has increased in the subject due to the fact that a high percentage of malignant prostate deceive the clinicians and pass undetected as Benign prostatic hypertrophy.

PSA is very effective as a tumor marker for prostatic cancer. It is useful for monitoring therapeutic efficacy, staging, prognosis, tumor volume evaluation, detection of recurrent disease, differential diagnosis, confirmation of tissue of prostatic origin, and, in some cases, for screening and early diagnosis.

Age-specific PSA reference ranges were proposed which were to be more sensitive in younger men and more specific in older men.

• e. threshold of 4.0 ng/ml lowered for younger men, improved sensitivity in the early detection of tumors.


• Second, age-specific PSA reference ranges were to improve the specificity of the PSA test by raising the PSA threshold for normal among older men2.


• In medical practice, most of the prostate abnormalities are diagnosed by measuring their volume Other indexes such PSA density (PSAD) were introduced thereafter to compensate the low specificity of PSA level.

Environmental Risk Factors-

Age is one of the strongest risk factors for the disease. It is more common in men over the age of 65, representing approximately 85% of all cases diagnosed. It has a much lower incidence in men younger than 50. The two principal androgens in adult men are testosterone and dihydrotestosterone. Androgen deprivation is known to decrease PSA levels and cause apoptosis of prostate cancer cells genome-wide scan of 91 prostate cancer family detected a susceptibility locus at chromosome 1q24, now known as Hereditary Prostate Cancer 1 or HPC1.Further studies have revealed this locus to be linked to younger age and more advanced stage at diagnosis and a higher grade of the tumor. It has also been suggested that the RNASEL gene on 1q25 might be responsible for the apparent effects.

AIMS AND OBJECTIVE-

The reason for our study is to correlate PSA and its distribution among different Prostatic Pathologies and to Study other screening tools useful in the accurate diagnosis and early detection of disease.

The Specific aims are :

1. To study the total PSA levels in patients with prostatic lesions.


2. To compare the PSA levels with USG findings and calculating PSA density.


3. To study age wise distribution of various prostatic lesions.


4. To compare the PSA levels & PSA density with the Histopathological diagnosis in prostatic lesions.


5. To evaluate the utility of PSA as a method of investigation in the diagnosis of the prostatic lesion.


6. To compare the PSA level with Histopathological grading (Gleason Score).

MATERIAL AND METHOD –

This Retrospective study was conducted in Department of Pathology at Sri Aurobindo Institute of Medical Sciences Indore from Jan2011-31st Oct 13.

Total No. of 216 histologically proved cases were included.
All the specimens of prostatic lesions received in the department for histopathology study in whom tPSA & USG findings were available were included in present study.

Total 59 cases of prostatic lesions were studied whose both PSA value and PSAD were available.

Serum PSA was done on Immunoassay on Elecsys 1010/2010, Sandwich principle with total duration: 18 min, Measuring (reportable ) range 0.002 (Elecsys 2010) or 0.006 for (Elecsys 1010) –

Cephalocaudal length (L) and diameter by HxWxLx/6.

The PSAD (the ratio of tPSA to prostate volume) was calculated.

OBSERVATION AND RESULT-

A total 216 patients were recruited in the period of 2011 to 2013, 157 were excluded because of absence of data regarding Prostate volume, PSA levels or Histopathological results. Thus 59 patients remained in the study.

Among the 59 patients, the prevalence of cancer was 8.26% (14).The remaining 26.5% (45) patients presented negative results for prostate cancer.
Out of total 59 cases studied, 22(13%) were reported as BPH without Prostatitis, 22 cases (13%) BPH with chronic prostatitis and 14 cases (8.26%) as Adenocarcinoma and One case (5.9%) reported as Tuberculous Prostatitis.

In our Study, serum PSA was done in all 59 patients. On grouping PSA with Histopathology diagnosis, BPH without prostatitis 7 cases (53.8%) had serum PSA in the range of 0-4ng/ml and 6 cases(28.6%) 4-10ng/ml , 4cases (57.1%) 11- 20ng/ml and 5cases(27.8%) > 20ng/ml. BPH with Prostatitis diagnosis 6 cases(46.2%) in range of 0-4ng/ml , 11cases(52.4%) were in 4-10ng/ml , 3cases (42.9%) fall in 11-20ng/ml and rest 2cases(11.1%) >20ng/ml.

Adenocarcinoma 4 cases(19.0%) fall in range of 4-10ng/ml and 10 cases(55.6%) >20ng/ml.

One case Tuberculous had serum PSA >20ng/ml.

The lower bound of Age came to be 63.79 and upper bound was 69.21 with (95% CI for Mean), the Mean age is 66.50 years with (p = 0.032).

The present study showed that 45 cases having BPH without prostatitis formed the major type lesion in the study. BPH mean age 64.81 years SD ± 7.62, Chronic prostatitis mean age 63.77 years SD ± 9.8, Tuberculosis mean age 81years.
Shakya et al., (2003), in their study of 106 BPH cases, found 47.16% of cases between 71-80 years followed by 33.96% cases in 61-70 years.
DISCUSSION

The present study showed that 45 cases having BPH without prostatitis formed the major type lesion in the study. BPH mean age 64.81 years SD ± 7.62, Chronic prostatitis mean age 63.77 years SD ± 9.8, Tuberculosis mean age 81years.
Shakya et al., (2003), in their study of 106 BPH cases, found 47.16% of cases between 71-80 years followed by 33.96% cases in 61-70 years

In our Study, serum PSA was done in all 59 patients. On grouping PSA with Histopathology diagnosis, BPH without prostatitis 7 cases(53.8%) had serum PSA in the range of 0-4ng/ml and 6 cases(28.6%) 4-10ng/ml , 4cases (57.1%) 11- 20ng/ml and 5cases(27.8%) > 20ng/ml. BPH with Prostatitis diagnosis 6 cases(46.2%) in range of 0-4ng/ml , 11cases(52.4%) were in 4-10ng/ml , 3cases (42.9%) fall in 11-20ng/ml and rest 2cases(11.1%)>20ng/ml.

Adenocarcinoma 4 cases (19.0%)fall in range of 4-10ng/ml and 10 cases(55.6%) >20ng/ml. One case Tuberculous had serum PSA >20ng/ml .

In Present study the cutoff PSA of (6.24ng/ml) the Sensitivity was (92.9%) and Specificity (62.2%).As the PSA level was broken down into four ranges the Mean PSA for Benign 17.709 ng/ml and Malignant cases is 60.29 ng/ml (range 0- >20ng/ml). Adenocarcinoma 4 cases (19.0%) fall in range of 4-10ng/ml and 10 cases(55.6%) >20ng/ml. So, Adenocarcinoma cases PSA concentration skewed to the right, having PSA value >20ng/ml.

In present study PSA (P= 0.000) the cutoff PSA of (6.24ng/ml) the Sensitivity was (92.9%) and Specificity (62.2%).In our study Histopathology diagnosis, BPH without prostatitis 7 cases (53.8%) had serum PSA in the range of 0-4ng/ml, BPH with Prostatitis diagnosis 6 cases (46.2%) in range of 0-4ng/ml, Adenocarcinoma 4 cases (19.0%) fall in the range of 4-10ng/ml.

PSA having (p=0.688), PSAD (p=0.774), Prostatic volume (p= 0.412).

SUMMARY AND CONCLUSION-

1. This Retrospective study was conducted in Department of Pathology at Sri Aurobindo Institute of Medical Sciences & Postgraduate Institute, Indore from Jan 2011-31st Oct 13.Total No. of 216 histologically proved cases were included.


2. Total 59 cases of prostatic lesions were studied whose both PSA value and PSAD were available.


3. Clinical details, Age, USG findings, PSA levels & histopathological diagnosis with GLEASON grading in carcinoma were noted.


4. BPH mean age 64.81 years SD ± 7.62, Chronic prostatitis mean age 63.77 years SD ± 9.8, Adenocarcinoma having the Mean age of 72.29 years SD ± 12.21. Malignant age ranged from 65 years to 79 years.


5. In Present study, 45 cases were Benign lesion having BPH with or without prostatitis which formed the major category.


6. Commonest was BPH with prostatitis cases (39%), second commonest being BPH without prostatitis, third being Adenocarcinoma (23.7%).


7. BPH without prostatitis group maximum ( 31.8%) had PSA level 0-4ng/ml, In BPH with prostatitis group maximum (47.8%)had PSA level 4-10 ng/ml range and cases of Adenocarcinoma group maximum patients had PSA level >20.0 ng/ml (71.4%)

Abbreviations: ASAP, atypical small acinar proliferation; DRE, digital rectal examination; PIN, prostatic intraepithelial neoplasia;

PSA, prostate-specific antigen; PSAD, PSA density; PSADT, PSA doubling time; PSAV, PSA velocity.

Author – ¹Dr Gaurav Pawar, MD Pathology, ²Dr Kapil Gupta, MD, Pathology ³ Dr. Monal Dixit, MD Pathology

Dr. Gaurav Pawar,

The author is MBBS, MD, (Pathology) and is Lab Head and Consultant Dept of Pathology, Metropolis Healthcare. He is a member Editorial Board, Pathology at Specialty Medical Dialogues.