Clinical significance of prostate specific antigen measurement

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Prostate cancer is seen most commonly in the UK men, 25% of the total cancer cases are of prostate cancer (Ian, 2010). Every year about 36000 men in UK are diagnosed with the prostate cancer. In Great Britain alone from last 30 years the prostate cancer affected rate is nearly tripled and the PSA(Prostate Specific Antigen) test has widely spread. Worldwide about 670000 men every year diagnosed with prostate cancer. More cases are registered in USA, Australia, Europe and New Zealand and the cases are low in East and Central South Asia (Cancer Research UK, 2010). In the progression of the PCa(Prostate Cancer) it has been given clean importance to the clinical detection and metastasising the cancer. Many of the recent studies on the PCa are focused in role of the stromal cells progression and metastasising. The progression of the PCa can be critically modulated by the dynamic phenol typical changes by observing the communication between stromal cells and including bone(derived), smooth muscle, vascular endothelial, osteoblast and fibroblast cells (Mark, 2005).

The aetiology of the PCa is fundamentally unknown, hormonal and diet factors might have an indirect influence. PCa is not common in Japanese living in Japan, but Japanese living in the Hawaii have the PCa and Hawaii whites also have the high risk of PCa. So this study shows that the migrant population had the risk of tending towards the PCa. This shows that the environmental factors would have contributed to the large risk difference between the countries (Sergio, et al., 2005).


BPH- (Benign Prostate Hyperplasia) is considered for the prostate enlarging because of the epithelial propagation which leads to the carcinogenesis BCL- 2, and anti apoptotic protein (Sergio, et al., 2005). Usually to know the expression of the gene is hard to compare the tumour with the normal sample by using the Microarray analysis, it requires a cell specific comparison. Cell communication pathways are active in PCa which are identical for the finding the gene expression in tumour epithelial and adjacent stroma. LCM(Laser Capture Microdissection)is used in the previous study of gene expression between stromal samples. Additional studies are made by using different tissue sources like formalin fixed paraffin embedded tissues, frozen biopsies and cDNA arrays platforms (Jennifer, et al., 2010).due to number of the genetic changes. Prostate carcinoma is classified according to the seriousness of the cancer i.e. T2 and T3 stages- T2 is the tumour occurring within the prostate and T3 will affect the adjacent tissues also (Jennifer, et al., 2010). While some of the genes are identified to be mainly involved in the HPC-(Hereditary Prostate Cancer), the gene locus that is first identified is HPC-1 it is Hereditary Prostate Cancer - 1 in the 1q 24 - 25 region. Oncogenes like Myc are amplified to inferior the prognosis. There are also tumour suppressor genes namely PTEN, p53 or RB1 can be inactivated or mutated. Some of the other genetic changes can undergo apoptosis pathway, which make over expressions of FAS-(Fatty Acid Synthetase), p53,

Many studies are made to find out the cause of the PCa disease. One of the most possibility of causing disease is through inheritance of the gene that cause PSA, some of the genes show the higher penetrance whereas some show low penetrance or polymorphism. From the discovery of the first genelocus HPC1 for which the allele is RNASEL many other genes which involve in PCa are identified. The genes which mainly involve in the PCa are CAPZB, EPAC2, CHEK2, PON1, MSR1, VITAMIN D Receptor and RNASEL. In BRCA2 may increase the risk of PCa if its germline mutation occurs (Dong, 2006). 5α reductase type-2, androgen receptor and steroid hydroxylase are the genes reported the genetic polymorphism and involve in androgen metabolism. PCa in African and European population genetic variation is identified on the chromosome 8q24 in which the variation is in high frequency and it is possibly could be the reason PCa is high incident in African American then American Europeans (Jan-Erik, and Gunnar, 2008).


In the early of the prostate cancer the symptoms are not found and during the affective PSA screening it only diagnosed only during the routine check up. Sexual intercourse must be avoided for the 3 days PSA test priority and it is highly recommended to get the affective result of the PSA test. Prostate cancer symptoms are similar to the prostatic hyperplasia like frequent urination, blood in the urine, difficulty in starting urination, painful urination, maintaining steady stream of urine and increased urination during nights. Prostate gland surrounding the prostatic urethra will cause urine dysfunction associated with PCa. Difficulty in the erection and painful ejaculation of the semen will be causing problem in the sexual function and performance due to PCa, as the vasderferens deposits seminal fluid in the prostatic urethra and so secretions of the prostate gland itself contains semen contents. And the advanced PCa can spread to the all the surround area around prostate gland which may cause additional symptoms. But the most common symptoms are bone pain, pain in ribs, pelvis and vertebrae. If the PCa affected the spine it will compress spinal cord, faecal and urinary incontinence and leg weakness.

The diagnosis techniques of the prostate cancer are:

PSA testing is a one of the mainly used PCa testing which detects the raise in the PSA levels in the blood. If the PSA levels are high it shows the presence of the prostate cancer. This test is able to detect the presence of the PCa even in the early stages. But about 20% of the individuals will not be screened for the rise of the PSA level but they do have the cancer. And like wise 65% of the men will be screened the presence of the high PSA levels but really they don't have the cancer. This is caused due to in older people PSA levels normally tend to rise (Stacy, and William, 2007).

Digital Rectal Examination as the prostate gland is very close to the rectum any surface change inside the rectum is observed by inserting the finger in to the rectum. As the PCa will make the gland harder and bumpy. Biopsy is also a type of assay can detect PCa by considering number of factors which includes PSA levels, Digital Rectal Examination and risk factors associated with PCa like age, ethnic group and family history. And most commonly used is TRUS Biopsy - Transrectal Ultrasound Biopsy which involves ultra sound scanner to picture the PCa and s needle to take the sample of the prostate tissue which is a very painful procedure and may cause infection (Sergio, et al., 2005).

Gleason Score is a grading given to the tissue samples of the prostate collected in the biopsy procedure by studying them in the laboratory lower scores will be less likely to spread like if the score is 6 or less and if it is 8 or above cancer will spread significantly (Jingjing, et al., 2010).

There are two other common tests used in PCa detection they are MRI - magnetic resonance imaging scan which take picture inside the body around the prostate gland region with the help of magnetic waves. And the other is Anisotope bone scan with the help of radiation it detects any abnormality in the bone and tells whether cancer is spread to bones or not.


A wide range of research was been done on the literature from the previous findings to the present situation and approach of the prostate cancer and the PSA test. Many book and journals are studied, analysed and the information is collected. The book and journals are collected from the university library, e-journals and the e- book were taken from the scientific websites and scientific databases which are assessed with the help of the university links. Lots of old values and the new values comparison was done and discussed in the report. The test standards have been updated which standards are internationally recognized, according to the data collected after analysing those data table and the graphs have been plotted added in to the report.

The materials are taken like from books Prostate Cancer Methods and Protocol - by Pamela, Prostate Cancer Diagnosis and Treatment - Published by the National Collaboration Center for the Cancer 2008. Urological Cancer In Clinical Practice - by Jonathan Waxman, Prostate Cancer diagnosis and treatment - Published by NHS 2008.Guidelines on Prostate Cancer - by Heidenreich, 2007

And the some of the research journals, e-Journals and scientific web sites etc.


In the case of the early or the local PCa which is not yet spread to the outside of the prostate gland there are some common treatments.

Surgery is the process which involves the surgically removal of the prostate gland it might be only the infected area or the whole prostate gland. Sometimes it might involve in the some of the areas near to the prostate if it is necessary, it is known as prostatectomy. In surgery the local lymph glands will be also removed if necessary to remove the cancer completely by sparing the nerves system and the muscles. There are some of the other surgeries which involve cryotherapy and robotically assisted surgery. Surgeries are mostly done for the men of the age under 70 conformed prostate cancers by PSA test and DRE.

Active Surveillance it involves the different type of treatments by putting the close watch on the progression of the disease and treating accordingly.

Cancer cells can be killed using the radiation and the prostate cancer is treated by the different types of the radiation therapy like external beam radiation therapy and by implanting very small radioactive seeds by the help of brachytherapy or using radiosurgery.

In the case of the Advanced or the metastatic Prostate Cancer the treatments will be different because in this case the cancer is serious and it is spread to the other parts of the body. So the common treatments for this satiation are;

Chemotherapy and Radiotherapeutic type of medication is use which is toxic to the cancer cells it is mainly use if the cancer cells becomes resist to the hormonal therapy.

Hormone therapy in this treatment the testosterone is inhibited by using drugs.

HIFU - High Intensity Focused Ultrasound in this treatment high intensity of the sound waves are focused on the prostate and due to it intense heat produced which destroys the prostate.

After these treatment the rise of the PSA levels is determined and again treated accordingly with CAM - Complementary and alternative Medicines in addition mainly after surgery or the radiation therapy it involves the influencing the mind of the patient or giving supplements or physical therapies.


PSA is a single chain serine protease of approx. 30kDa which is expressed at very high levels in the normal human's prostate epithelium, in most of the cases the majority of the epithelial cells are prostatic tumour cells and hyperplastic nodules. And it shows the concentration levels as 0.2 - 5 g/l so the prostate derived protein is abundantly in human seminal fluid. Originally Hare, et al., in the year 1971 isolated first gamma semino-protein. Li, et al., isolated and characterised the similar protein like PSA and called it as the E1 antigen and Sensabaugh, et al., fond the semen specific protein called as p30 which is useful in identifying sperm in forensic. And whereas Wang, et al., in the year 1979 isolated the Prostate Specific Antigen- PSA from the normal prostate tissue it is hypertonic and malignant but is unable to detect in any other tissues of the human (Charlotte, and Hans, 1996).

The gene coding of the PSA is situated on the long arm of the chromosome 19 in between 60 - 70 kb in which the genes of the kallikrein(hK1) and glandular kallikrein (hK2 or hGK1) human tissue is located (Riegman, et al., 1992). Three different forms of the serum is found in PSA one is free PSA with molecular weight of 30 kDa and second one is bound to alpha 2 macroglobulin (A2M - PSA)with the molecular weight of 780 kDa. And the third one is bound to the alpha anti chymotrypsin (ACT - PSA) which is having the molecular weight of 90 kDa. Both A2M and ACT were produced by the liver and they are extracellular protease inhibitor. The amounts of the traces of PSA bound to the Alpha1 antitrypsin and inter alpha trypsin inhibitors but they are not in the tough form according to the clinical relevance. A very limited number of the alpha1 antichymotrypsin are formed when its complex formations are exposure to the antigenic epitopes of PSA. But the complex formation formed by the alph2 macroglobulins covers the present identification of the antigenic epitopes of PSA. Predominant immunoreactive form is ACT-PSA, 5-30% immunoreactive is free PSA (Nash, and Melezinek, 2000).

The PSA Matabolism is not properly understood. The relative molecular weight of the free PSA is very low and they can't be eliminated through renal passage. The free radical elimination is assisted with 2 compartment model with half life initially like approx. 2-3 hours; the half life can be 20-25 hours after the removal of the gland 4 hours before. The half life of the ACT-PSA is 2-3 hours in blood and liver is the site for metabolism.


The useful markers are used to demonstrate the diagnosis stages of the PCa by using serum PSA. However, it has limited values particularly when it comes to the patients intermediate PSA levels. Till the elevated serum PSA found in the patients with (Benign Prostatic Hypertrophy) BPH and prostatitis. For the increase in the diagnosis and staging of PCa significantly, the several parameters related to PSA are to be elevated such as PSA Density (PSAD), PSAVelocity and free total PSA ratio. Despite of the results of the pervious study, no method is sufficiently reliable to make the clinical decision making in the individual patients selective between benign and malignant prostate disease or to predict the extant of PCa (Isao et al., 2001).


Specificity is one of the important measurements for any of the test. It tells the probability of the presence of the cancer or the test will be normal. Like if the PSA specificity is 80% then he has a 20% chance to not get the prostate cancer and he need to be under go Biopsy.


Cancer Vs No Cancer

Aggressive cancer Vs other

















The PSA is the protein that is produced by the Prostate gland, and PSA test is used to measure the levels of the PSA in the blood. Doctors usually use PSA test and DRE together for the screening the PCa. The rise in the levels of the PSA will show the presence of the PCa in the patients.

PSA test was first approved by the US FDA - Food and Drug Administration and using the prostate screening DRE which was developed by the Hybritech. More than 6,600 men were clinically studied and found that the 4.0 ng/ml is the cut-off for the Hybritech normal test. So in this method of the PSA testing (Hybritech) the 4.0 is aligned as the standard and men whose PSA is lower than 4.0 is not referred to the further test like Biopsy by the physician instructions. These standards are known as the Hybritech standards and other manufactures also taken this standard into the account and recommended cut-off of 4.0 and it came in to recognition from mid 1990's.

But some of the test results are recognized as they are consists of the different test results due to the different manufacturers. So some of the researchers have calibrated a common standard for the results of the different PSA tests, and the Standard have been recognised by the WHO - World Health Organisation which is also known as the WHO standard for PSA test. The WHO standards are determined based on the molecular weight of the PSA, and the molecular weight is determined that it is 20% higher than compared to the Hybritech standards. But Hybritech process is widely used test for determining the PSA levels.

So in the WHO test the weight of the sample is taken into the consideration for the measuring the PSA and it is a higher weight measure, the WHO test will show the lower PSA concentration levels than that of the Hybritech test with the same sample. This makes to change the Cut-off point which is actually 4.0 which is set considering the Hybritech test method by referring to the above condition. The Cut-off point must be lowered 20 % then the actual 4.0 for the Hybritech test. But unfortunately everybody still uses the 4.0 as the Cut-off point for the both tests. The use of the WHO standards was started from 2000 in report and everyone began to take the WHO standards in the consideration for patients result determination.

After the introduction of the WHO standards the scientific studies are done to note the differences in the results between the two tests (Klee et al. 1999). Journal of Urology in 2004 has published a comparable study on the different cancer detection "The potential clinical impact of this variability on cancer detection is significant" (Link et al. 2004). After comparing these tests they have confirmed that there is a 22 percent gap difference between the tests, and presented the report at American Urological Association's annual meeting in 2008 (Loeb et al. 2008).

As we take this approx. 20 percent gap difference into the consideration it means that if the man has got 4.0ng/mL in the Hybritech test report the person should receive only 3.1ng/mL in the WHO test. But many of the medical associations still follow the 4.0ng/mL strict cutoff value. They are unaware that the cutoff value will not be same for the all tests. Which means the person who gets the result between 3.1ng/mL and 4.0ng/mL in the WHO test will not be taken into the consideration for the further testing quicker that they should have done. The problem is not coming on the process of which test is better, it is due to the lack of proper interpretation on the different cutoff scores.

PCPT (Prostate Cancer Prevention Trial) Data shows that there is a possibility of the + ve prostate biopsy or any other high graded disease if the Gleason score of ≥ 7 and rise in the PSA levels. There is no proper cut-off value up to PSA levels 4.0 ng/mL. There is controversy with the previous estimation for the risk of the men with the prostate cancer even if the men PSA levels is ≤ 4.0 ng/mL still there is a use of systemic biopsy. PCPT has conducted study on population and published that there is a risk of 27% when PSA level is 3.1 - 4.0 ng/mL, 24% when PSA is 2.1 - 3.0 ng/mL and 17% when PSA is 1.1 - 2.0 ng/mL. (Gerald et al. 2006)

The graph shows the percentage of the men that can be affected with the prostate cancer even even if the PSA levels are ≤ 4.0 ng/mL and other high grade disease.

The devise works on the principle of the detection of the PSA levels that are present in the blood and it is the most effective way of measuring the PSA levels more effectively If the PSA levels are less than the 4ng/mL is not effected by PCa, if it is more than 4ng/mL then he is effected with the PCa. The biochemistry involved in the PSA, PSA is also known as p30 antigen, seminin, γ - seminoprotein, kallikrein III, and semenogelase. Prostate gland manufactures single chain serine protease 34kDa.

PSA is present in the ejaculated when the semen liquifies then the seminal coagulum and sperm freely swims. The PSA instrument dissolves the cerical mucous cap allowing the entry of the sperm inside the instrument for estimation.

7.1) Testing principle

The principle of the PSA test is based on the sandwich principle it is an enzyme immunoassay the process consists of two step paramagnetic particle assay. The reagent and the sample are added to sequence the assay in the following manner step by step.

The sample taken from the patient is incubated monoclonal antibodies (PSA) bound to the paramagnetic particles and it form an antibody-antigen complex.

This antibody-antigen complex is conjugated with the alkaline phosphatase (ALP) and reacts with the paramagnetic particle to form a sandwich complex. And every time the unbound materials are washed away

And the remaining sandwich complex is added with the chemiluminescent substance to emit light and the light is measured with luminometer.

Antibody - coated Sample antigen antibody-antigen complex

(Paramagnetic particle)

Antibody-Antigen ALP Antibody Sandwich complex



Sandwich Complex Light

The specificity of the PSA test can be increased by retaining high sensitivity in the 2.5 ng/ml - 10 ng/ml diagnostic grey zone. Some of the refinements in the PSA evaluation are proposed which includes the measurement of the free/total PSA ratio, PSA density, PSA velocity and by age specific PSA reference ranges.


The PSA in the body is divided according to the complexity in its structure If the PSA in the blood is present bounded to the enzymes it forms complex structure and some are freely circulating which are referred as free. The combination of the complexed and free PSA levels is generally called as the Total PSA or tPSA. Free PSA or fPSA is the percentage of the PSA present in the blood which is not bounded with the enzymes. Nowadays the doctors are proceeding the man to the further test even if the fPSA is less than 25 %. This is very helpful to the men who are confused weather to get biopsy test or not. Whereas it is normally done when the PSA levels are between 4-10ng/ml and DRE is negative in the results.

Complexed PSA or cPSA is bounded to the enzymes and the measure is accurate like Total PSA and it can be also be better in short listing the patient for proceeding to the further tests. The cutoff levels are also different for the cPSA. If the level of the cPSA is 2.2ng/ml then the level of tPSA will be equal to 2.5ng/ml, so it is very important to know what your testing cPSA or the tPSA.


In the prostate cancer patients the fPSA / totalPSA ratio is higher than prostatic hypertrophy (Stenman et al. 1991). Free PSA assays comparison with the ACTPSA (alpha1- antichymotrypsin Prostate specific antigen) complex (Kikuchi et al. 2006) suggest that free PSA to Total PSA ratio is better in the accuracy than the ratio of cPSA to Total PSA ratio (Christensson et al. 1993, Pettersson et al. 1995). This finding reason is unknown but may be related to the local production of ACT by prostate cancer cells not by prostatic hypertrophy cells (BPH) then the PSA point of secretion complex (Bjork et al. 1994). Utilities have been investigated by several studies for assessing fPSA / tPSA ratio in detecting the prostate cancer. And this process is useful in the discrimination between BPH and prostate cancer, the ratio is higher for the BPH and lower for prostate cancer (Catalona et al. 1995, Chen et al. 1996, Partin et al. 1996, Prestigiacomo et al. 1996). Asymptomatic chronic prostatitis is also taken into the consideration which has a possibility of reduced ratio of fPSA/tPSA (Jung et al. 1998). In the study many number of cutoff values have been applied for fPSA/tPSA ratio ranging 14 % - 28 % for maintaining the sensitivity at least 90 % and the specificity range is resulted from 19 % - 64 % with the help of the specific cutoff value that is found out during these studies and it can be determined whether to perform biopsy or not to the patient. This would prevent about 19 % - 64 % of the negative biopsy cases of cancer.


If the total PSA levels are high there is a much chance for an individual to be diagnosed with the prostate cancer or having the advanced stage of the prostate cancer (Catalona et al. 1993). There is upto 80 % PPV - positive predictive value chances are there for the detection of the prostate cancer if there is an increase in the total PSA like values of 10 - 20 ng/mL. When the total PSA is compared with the fPSA/tPSA ratio, fPSA/tPSA ratio provides little additional information over this range but at the range of 2.5 - 10 ng/mL total PSA shows useful information.


Benson and colleagues in 1992 first raised the concept of the PSA density to differentiate the BPH and the prostate cancer. There approach is based on the fact that the benign epithelial cells are in the continuous along the prostate duct will help in prevention of the leakage much of the PSA in to the streams of the serum as the cancer cells where the duct will not act as the conduit for secretions. The concentration of the PSA per every benign epithelial cell will show the lesser variability then the cancer cells. That why there should be a limit for the prostate cell count for any given prostate volume to be situated and accordingly the upper limit for the serum PSA which has the benign origin. If this level is achieved it is said to be that gland is occupied by the cancer cells. In one of the study conducted on the 61 patients who are affected with the prostate disease after they are clinical conformation about the prostate gland. The magnetic resonance imaging MRI was taken for the BPH in order to assess the PSA density, it seems to be the dimensions are higher in the surgical specimen in the patients with the prostate cancer than that of BPH. Prostate cancer patients have 0.581 and BPH patients have 0.044 PSA density. And it seems that 41 patients have the prostate cancer and remaining 20 patients has the BPH. In 34 patients the PSA density is > 0.1 in which 33 of them had the prostate cancer. And there is a less ability for the PSA density in the range 0.05 and 0.15 to predict the cancer as 6 patients had cancer and 5 of them had BPH in this range. There are 2 patients who have cancer even in the less value then 0.05 (Benson et al. 1992).

To differentiate between the BPH and the Prostate cancer 0.15 is been taken as the cutoff value (Bazinet, et al. 1994) even though some of the studies not shown any beneficial approach (Brawer, et al. 1993). Nearly about 5000 men were studied using the PSA density as > 0.15 for the detection of the early prostate cancer in the patients and observed it has increased the specificity but it has missed the half of the tumours (Catalona et al. 1994b). It seems to be difficult to estimate the accurate prostate volume where the correlation coefficient is about 0.61 and observed the transrectal ultrasound volume vs pathological prostate weight. And it was concluded that men has 4.1 ng/mL to 9.9 ng/mL PSA levels and normal DRE and Transrectal Ultrasound Findings so the patient procedure for the biopsy must be based on the serum PSA than PSA density.

Refinement of the PSA density is needed to remove this error, so to rectify these errors we can take use of the transition zone prostate PSA density. Here we must observe when the serum arrives at the transition zone not near the benign prostate (Hammerer et al. 1995). BPH will be becoming hyperplasia of the transition zone and consent PSA is produced peripheral gland and which lead to the prostate gland enlargement because of the BPH (Lepor et al. 1994). PSA will be increased due to the BPH if it above the cutoff value of the PSA transition zone which further lead to the suspicion of the prostate cancer. The cutoff value is 0.35 ng/mL between the cancer and BPH(Creasy et al. 1997). Many Serum PSA studies shows that prostate cancer prediction is increased with the assessment of the transition zone PSA density of 4 - 10 ng/mL (Kurita et al. 1996, Zlotta et al. 1997). The specificity of the Serum PSA can be increased by using the low transition zone PSA density of 0.25 for the detection of the prostate cancer with the serum PSA levels of 4 - 10 ng/mL which much useful then the PSA density, % free PSA and PSA velocity. But only when the gland volume increased above 30 ml, and have 95 % sensitivity in detection, 47 % of unnecessary biopsy can be rectified compared with the fPSA/tPSA ratio.


The detection of the PSA velocity was first proposed by the Carter et al. (1992) and he differentiated the presence of prostate cancer between with or without men. In the study done on the PSA they have found out that rise of the PSA levels in the patients with the prostate cancer is higher than the PSA level rise for the patients with BPH. It is a very high PSA velocity about the level higher than 0.75 ng/mL per year. It was observed in the patients for 9 yrs before he was affected with the prostate cancer clinically (Carter et al. 1992). But this application is applied very limitedly but by the intrinsic biological variability and by maintaining same assay manufacturer (Smith & Catalona, 1994). In one of study about PSA velocity they found the 12.5% of the men has a annual PSA increase higher than 0.75 ng/mL per year and when two year study was considered only one person has a higher than 0.75 ng/mL increase per year (Kadmon et al. 1996). Over all PSA velocity is can be most useful for the patients whose PSA levels are normal in the initial testing. But this process cannot br useful for the patients whose PSA levels are between 4ng/mL to 10ng/mL and should undergo biopsy.

9) Precision and Accuracy

The precision of the depends on the level of the PSA in the blood of the patient if the PSA levels are less than the 4ng/mL is not effected by PCa, if it is more than 4ng/mL then he is effected with the PCa.

The overall aim of PSA testing is to recognize localized prostate cancer when potential curative treatment can be provided. In some instances cure is not possible and in these cases treatment may extend life. However, there are some issues that should be considered with the PSA test because the value of using PSA as a tool to screen men is very difficult to assess

10) Advantages and limitations

The PSA Test is very potential and provides more information about the cancer before the symptoms are noticed which helps in the early detection and try to cure the disease or extent the life span of the. On detection PSA diagnostic result alone will not be sufficient it must be further clarification must be need to it by using further methods. So there is the limitation involved in this PSA test there is a limitation with the specific tumer marker also that is used in the PSA. Some of they can turn out to be a false results, which may lead the patient to the depression (Ian, 2010).


The age specific reference range report that in both of the types that is cPSA and tPSA will always correlate with the patient's age, and several workers of fPSA group correlate directly to their age. The concentration of the serum molecular form increase every 3% per year and when we compare all the three tPSA, cPSA and fPSA their ratio will not correlate with the patients age. In Female the PSA levels are very low but in the Older man the PSA levels are high and the study say that PSA levels increase as the man gets the prostate volume may increase as the age will get advanced (Hans, et al., 2007).




50 - 59


60 - 69













5th percentile










95th percentile










The table is adopted from (Carter et al. 1992).


Gene therapy