Early detection of prostate cancer: evaluating the diagnostic performance of prostate specific antigen by comparing with histological technique among africans

This study was conducted to investigate the diagnostic performance characteristics of prostate specific antigen (PSA) by comparing serum PSA value with histological findings in patients suspevted of having prostate cancer in Aminu Kano Teaching Hospital. Nigeria. Clinical and Laboratory records were examined and collated for serum PSA values, together with histological findings of biopsy specimen, clinical diagnosis, age of patients, and mode of presentation. The serum PSA values were determined by ELECSYS 1010 autoanalysers Roche, Germany based on electrochemiluminescence immunoassay technique. The results show that serum PSA values increase with age in the assymptomatic non-cancer patients who came for medical check up but were within normal limit. In prostatic disease conditions PSA values were raised in benign prostatic hyperplasia 35.957± 4.0315ng/ml, in undifferentiated carcinoma 56.22±4.295ng/ml and adenocarcinoma >100ng/ml as compared to the normal range (0–4ng/ml). These cases were confirmed by histological diagnosis. It is concluded that PSA evaluations is a sensitive marker for prostate cancer but because of various other conditions that affect serum PSA concentration, other methods of investigations such as Digital Rectal examination, Trans Urethral Ultra-Sonography and histological examination should be combined to confirm diagnosis. Prognosis of patients will be better if early diagnosis is made.     

The changing scenario in diagnosing prostate cancer

Fifty patients were evaluated for serum total PSA (Prostate Specific Antigen), free PSA (f-PSA), free/total PSA ratio (f/t PSA ratio) and TPS^TM (Tissue Polypeptide Specific Antigen). Fifty patients were clinically evaluated and categorized into BPH (benign prostatic hypertrophy) and CaP (carcinoma prostate) with twenty-five in each category before the serological examination. Serum total PSA concentration is elevated in 80% of BPH cases while it was elevated in all cases of CaP. With total PSA>10ng/mL, f/t PSA ratio was not applicable. For TPS^TM, a cell proliferation marker these values were 32% and 92% respectively. The advanced cases of CaP were reflected by the pronounced elevations of PSA and TPS^tM while f/t PSA ratio was much below the cut-off limit (cut-off limit=0.14). The data suggest that whentotal PSA concentration <10ng/mL, f/t PSA ratio plays a very important role in discriminating BPH and CaP. However, TPS^TM can be used as a valuable adjunct in diagnosis and follow-up of prostate cancer patients, especially in differentiating benign from malignant cases.     

Prostate specific antigen in patients of benign prostate hypertrophy and carcinoma prostate

Prostate Specific Antigen (PSA) has emerged as the most applicable and important tumor marker for carcinoma prostate. In the present study PSA was determined in serum of healthy subjects, patients of benign prostate hypertrophy (BPH) and Carcinoma Prostate (Ca−P) to evaluate its diagnostic efficiency in day to day management of prostate cancer patients and in differentiating patients of early prostate cancer from those with BPH. Receiver operating characteristic curve (ROC) revealed 2 ng/ml and 10 ng/ml cut off serum PSA level for BPH and untreated carcinoma prostate patients (Ca−P). An extremely significant increase (P<0.0001) was observed in mean PSA concentration in BPH patients and adenocarcinoma prostate patients when compared to healthy males. Clinical relevance of PSA was highlighted by a case study of cancer patient prior to any therapy till death.     

A comparative study of tumor markers of adenocarcinoma prostate

The present study deals with the evaluation and comparison of the tumor markers for prostatic carcinoma—The Total Acid Phosphatase (ACP Total) and its Prostatic Fraction (ACP PF) estimated by the enzyme kinetic method, an immunoreactive Prostatic Acid Phosphatase (PAP) and Prostate Specific Antigen (PSA) estimated by enzyme immunoassay. The comparison of all four markers revealed that there was no perfect positive correlation between any of these four markers. PSA had shown a better correlation with ACP Total and its prostatic fraction ACP PF. No correlation was observed between PSA and PAP. Of the four markers PAP exhibited a very low sensitivity, positive and negative predictive values. PSA had shown an absolute specificity, sensitivity, positive and negative predictive values for adenocarcinoma prostate. PSA levels in all phases of disease showed a 100% correlation with disease status. Being a marker with very high tissue specificity and sensitivity, it is revolutionizing the diagnosis of prostatic carcinoma. Hence, it could be used effectively for screening of elderly people over 50 years of age who are at high risk for developing prostatic carcinoma for early diagnosis of this disease.     

Changes in Serum PSA During Normal Menstrual Cycle

Prostate specific antigen (PSA) has long been used as a biological marker for prostatic cancer. Recent studies have demonstrated that PSA synthesis can be induced by steroid hormones in several tissues of women. Menstrual cycle is regulated by the cyclic variation of estradiol and progesterone. This study was undertaken in order to study the correlation of serum PSA to both these corpus luteal hormones. 110 serum samples and 10 saliva samples were collected from healthy women aged 18–45 years of age having normal menstrual cycles. Active PSA DSL-9700 ultrasensitive kit with detection limit 0.001 ng/ml was used to analyze PSA. 38.2 % of all serum samples and 10 % of saliva samples had detectable concentrations of PSA. The serum PSA was highest during mid follicular phase (between 4th and 8th days of cycle). Variation in PSA levels seemed to follow the variations in progesterone with a lag period of 12–14 days, but did not appear to bear any relationship with the estradiol levels.     

Advances in urinary protein biomarkers for urogenital and non-urogenital pathologies

The discovery of protein biomarkers that reflect the biological state of the body is of vital importance to disease management. Urine is an ideal source of biomarkers that provides a non-invasive approach to diagnosis, prognosis and prediction of diseases. Consequently, the study of the human urinary proteome has increased dramatically over the last 10 years, with many studies being published. This review focuses on urinary protein biomarkers that have shown potential, in initial studies, for diseases affecting the urogenital tract, specifically chronic kidney disease and prostate cancer, as well as other non-urogenital pathologies such as breast cancer, diabetes, atherosclerosis and osteoarthritis. PubMed was searched for peer-reviewed literature on the subject, published in the last 10 years. The keywords used were “urine, biomarker, protein, and/or prostate cancer/breast cancer/chronic kidney disease/diabetes/atherosclerosis/osteoarthritis”. Original studies on the subject, as well as a small number of reviews, were analysed including the strengths and weaknesses, and we summarized the performance of biomarkers that demonstrated potential. One of the biggest challenges found is that biomarkers are often shared by several pathologies so are not specific to one disease. Therefore, the trend is shifting towards implementing a panel of biomarkers, which may increase specificity. Although there have been many advances in urinary proteomics, these have not resulted in similar advancements in clinical practice due to high costs and the lack of large data sets. In order to translate these potential biomarkers to clinical practice, vigorous validation is needed, with input from industry or large collaborative studies.Key words: urine, protein, biomarker     

Racial and ethnic variation of PSA in global population: Age specific reference intervals for serum prostate specific antigen in healthy South Indian males

The serum PSA is universally accepted as the useful and clinically relevant tumor marker for monitoring therapy and identifying early recurrence in patients of carcinoma prostate throughout the world. However, application of serum PSA is limited to screening for early adenocarcinoma prostate among males above fifty years of age. Serum PSA concentration varies from one population to another in different parts of the world. Many groups of workers have selected 4 ng/ml of serum PSA as upper limit of normal range without giving due consideration for age specific increase in serum PSA. There is no single report available on normal decade wise age specific reference intervals for serum PSA in Indian males. The present study is undertaken to establish age specific reference intervals in healthy Indian males from 20–89 years belonging to subpopulation of Andhra Pradesh from South India. Our results revealed lowest concentration of 95 percentile serum PSA in Indian males compared to other populations globally. Contrary to this, healthy Afro Americans were found to have highest concentration of serum PSA compared to all other populations.     

Status and Interrelationship of Zinc,Copper, Iron,Calcium and Selenium in Prostate Cancer

Deficiency or excess of certain trace elements has been considered as risk factor for prostate cancer. This study was aimed to detect differential changes and mutual correlations of selected trace elements in prostate cancer tissue versus benign prostatic hyperplasia tissue. Zinc, copper, iron, calcium and selenium were analysed in histologically proven 15 prostate cancer tissues and 15 benign prostatic hyperplasia tissues using atomic absorption spectrophotometer. Unpaired two tailed t test/Mann–Whitney U test and Pearson correlation coefficient were used to compare the level of trace elements, elemental ratios and their interrelations. As compared to benign prostatic tissue, malignant prostatic tissue had significantly lower selenium (p = 0.038) and zinc (p = 0.043) concentrations, a lower zinc/iron ratio (p = 0.04) and positive correlation of selenium with zinc (r = 0.71, p = 0.02) and iron (r = 0.76, p = 0.009). Considerably divergent interrelationship of elements and elemental ratios in prostate cancer versus benign prostatic hyperplasia was noted. Understanding of differential elemental changes and their interdependence may be useful in defining the complex metabolic alterations in prostate carcinogenesis with potential for development of element based newer diagnostic, preventive and therapeutic strategies. Further studies may be needed to elucidate this complex relationship between trace elements and prostate carcinogenesis.     

Detection of Bone Metastases in Breast Cancer (BC) Patients by Serum Tartrate-Resistant Acid Phosphatase 5b (TRACP 5b), a Bone Resorption Marker and Serum Alkaline Phosphatase (ALP), a Bone Formation Marker,in Lieu of Whole Body Skeletal Scintigraphy with Technetium99m MDP

Bone metastases are a serious problem in patients with advanced cancer disease and their presence usually signifies serious morbidity prior to the patient’s death. In breast cancer patients the incidence of bone metastasis is observed to be very high at 70 %, as seen during post-mortem examination. Bone metastasis is difficult to diagnose, treat or follow clinically without radiological tools. This study was designed to evaluate the utility of a novel bone resorption marker–serum tartrate-resistant acid phosphatase 5b (TRACP5b) and the bone formation marker such as serum total alkaline phosphatase (ALP), in comparison with whole body skeletal scintigraphy with Technetium99m MDP for the diagnosis of bone metastases (BM) in breast cancer (BC) patients. This study is intended to help the clinician to diagnose bone metastasis without resorting to radiological tools, as they are not cost effective and carry the risk of radiation. Experimental design: Four groups of samples were analysed. 1st group consists 52 normal female (cancer free women), 2nd group consists 38 BC patients without bone metastasis, 3rd group consists 27 breast cancer patients with limited bone metastasis (3 or less than 3 skeletal lesions) and 4th group consists 35 breast cancer patients with extensive bone metastasis (4 or more than 4 skeletal lesions), conformed by whole body skeletal scintigraphy with Technetium99m MDP. One way ANOVA was used to compare serum TRACP5b and serum ALP among these groups. Both serum TRACP5b and serum ALP are not markedly elevated in limited bone metastasis but are strongly elevated in extensive bone metastasis (p < 0.0001). As seen in this study the biochemical bone resorption marker, serum TRACP5b, abnormally increased in extensive bone metastasis of breast cancer patients and can be used as a specific marker for bone metastasis in lieu of radiological tools.     

Serum Testosterone, 17β-Estradiol and PSA Levels in Subjects with Prostate Disorders

Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death as a result of cancer in men in the US and other parts of the world. There are conflicting reports on the serum levels of testosterone and 17β-estradiol (E₂) in benign prostatic hyperplasia (BPH) and prostate cancer. This study was designed to evaluate the serum concentrations of these hormones in patients with these disorders. Serum levels of prostate specific antigen (PSA), total testosterone and estradiol were determined in 228 subjects comprising of 116 subjects with BPH, 62 subjects with prostate cancer (CaP) and 50 age-matched apparently healthy controls, using ELISA methods. PSA levels were significantly elevated (p < 0.05) in BPH subjects than controls, while there was no significant difference (p > 0.05) in testosterone and estradiol levels of these subjects. PSA and estradiol levels were significantly higher (p < 0.05) in CaP subjects than in controls, while there was no observed significant difference (p > 0.05) in testosterone levels. CaP subjects had significantly raised PSA, testosterone, and estradiol levels than BPH subjects. The mean molar ratio of testosterone: E₂ was lowest among CaP patients (134:1) and highest among controls (166:1). Significant positive correlation between PSA and 17β-estradiol was observed in prostate disorders (BPH and CaP patients: r = 0.347; p = 0.000). Significant negative correlations between testosterone and PSA were also observed among BPH patients (r = −0.221, p = 0.049) and control subjects (r = −0.490, p = 0.000). No significant correlation existed between testosterone and PSA in CaP patients (r = 0.051, p = 0.693). Correlations between age and estradiol in both BPH and CaP were not significant (p > 0.05). This study has shown that, there was a significant increase in serum estradiol in CaP subjects, while the testosterone levels in both BPH and CaP subjects were not different from those of controls.     

Differential erythrocyte agglutination pattern in normal and cancer patients with Synadenium grantii root (Hook f) lectin

In the present study the property of lectin agglutination in blood on normal and different cancer patients has been observed. The purifiedSynadenium grantii root lectin was non blood group specific and its utility as a diagnostic tool in malignancy was studied. Hemagglutination (units/ml) of red blood cells of different types of cancer was compared with the normal control's red blood cells. Out of 113 total cancer patients, only a group of 29 breast cancer patients showed significant increase in titre value (P<0.05) compared to normal control.     

TPSTM a circulating tumor marker in breast cancer

Tissue polypeptide specific antigen (TPS) measures an antigenic determinant associated with human cytokeratin 18. TPS is a marker of tumor cell activity in contrast to markers related to tumor burden. The value of detecting circulating TPS lies in the early detection of recurrence by serial determinations and in the rapid assessment of the efficacy of the treatment. Pretreatment levels of TPS in patients with metastatic breast cancer are related with prognosis. Decreasing TPS levels during therapy monitoring indicate response and a fast response is correlated to favourable prognosis. Increasing TPS levels, in the presence of clinically stable disease or partial remission, predict disease progression with a considerable lead-time. Improved effectiveness in breast cancer management can be seen when TPS is used in combination with CA 15-3. When tumor marker determinations are applied in a proper way in the appropriate situation, the results can assist the oncologist. Thus monitoring of therapy in patients with metastatic breast cancer should be based upon serial TPS and CA 15-3 determinations in serum. The use of tumor marker determinations in the early follow-up interval following surgery to detect early tumor recurrence may be simpler, more sensitive and less expensive than imaging methods.     

Prostate Specific Antigen in Cord Blood

Recent studies have demonstrated the presence of prostate specific antigen (PSA) in cord blood of male as well as female babies. The placental progesterone and estradiol up-regulate the synthesis and secretion of PSA in Placenta. This PSA is presumed to play a role in intrauterine growth of fetus by virtue of its proteolytic action on several substrates including insulin-like-growth-factor-binding-protein-3, insulin chains and Interleukin-2. This study was planned with the objective of correlating the levels of PSA in cord blood to gestation at delivery, the type of delivery and gender of the fetus. Fifty-seven cord blood samples were collected from the umbilical cord during delivery or mid-trimester abortion and analyzed for PSA using ‘Active PSA DSL-9700 ultra sensitive’ kit employing two-site immuno-radiometric assay principle and having a detection limit of 0.001 ng/ml. Mean PSA levels in cord blood were found to be 0.112 ± 0.027 ng/ml. The concentration of PSA in cord blood was found to be higher in case of higher gestational age, male baby and operative delivery. 50 % of cord bloods for female babies had PSA below detection limit (range <0.001–0.460 ng/ml), while all the male samples had detectable PSA (range 0.11–0.973 ng/ml). Higher Progesterone levels found in prenatal maternal blood in case of male babies may be responsible for the higher cord blood PSA. Mean cord blood PSA was 0.150 ± 0.150 ng/ml in forceps delivery and 0.078 ± 0.012 ng/ml in normal vaginal delivery. Forceps delivery causes much more stress and strain as compared to a normal vaginal delivery, resulting in increased levels of adrenal glucocorticoids, and therefore, higher cord blood PSA.     

Serum gamma glutamyl transpeptidase in breast cancer

Gamma-glutamyl transpeptidase (gamma-GT) levels were estimated in the sera of patients with breast cancer and compared with those of benign breast diseases and healthy controls. Serum gamma-GT levels were found to be significantly increased in patients with breast cancer compared to the controls as well as benign breast diseases. The rise however, was nearly same in all the patients irrespective of histopathology of cancer but was directly related to tumour mass. After mastectomy the levels remained higher upto 3 months. In patients with cancer the rise in serum gamma-GT was significantly higher as compared to those with benign breast diseases. Although gamma-GT is an index of liver diseases, its high level in breast carcinoma suggests the release of the membrane bound constituents from different tissues even in carcinoma.     

Status of epidermal growth factor receptors family in hormone-dependent carcinomas of the breast and prostate with reference to serum lipids and lipoproteins

There are numerous growing evidences of resemblance between carcinomas of the breast and prostate. A total of 45 cases of these two hormone-dependent cancers along with appropriate controls were subjected for status of epidermal growth factor receptors as well as serum lipid profile. Paraffin embedded tissue sections from aforesald tumours were analysed by immunohistochemical staining for epidermal growth factor receptor (EGF-R), c-erbB-2 oncoprotein, estrogen receptor (ER) and progesterone receptor (PgR). Sera from same individuals were studied for serum lipid profile analysis. The study revealed that immunoexpression of all receptor proteins (EGF-R). c-erbB-2 was significantly higher in breast carcinoma. In addition, mean levels of triglycerides, total cholesterol, LDL-cholesterol were found to be significantly elevated while the level of HDL-cholesterol was observed to be lower among patients with breast cancer as compared to matched controls. Further, ER-positive breast cancer cases have significantly higher mean level of HDL-cholesterol when compared with ER-negative breast cancer patients. Contrary to this, no alteration in different serum lipid fractions was noticed among the patients with prostate cancer. However, a positive relationship was noticed between immunoexpressions of EGF-R and c-erbB-2 in prostate cancer.     

Stability of total and free prostate specific antigen in serum samples at different storage conditions

The present preliminary study was performed to find out stability of total prostate specific antigen (PSA) and free prostate specific antigen (FPSA) in serum of healthy males as well as in patients of benign and malignant disorders of prostate at various freezing and nonfreezing temperatures and at different duration of time. The results of our study indicated long-term stability of both the analytes in frozen serum. Serum total and free PSA were stable only for three to four days in regular refrigerators in unfrozen states. Clotted blood kept at room temperature (25°C–30°C) did not cause change in concentrations of both the analytes for twenty four hours.     

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis

Introduction

Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis.

Materials and methods

Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed.

Results

Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70–0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59–0.82], P = 0.042) as isolated test.

Conclusions

We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation.Key words: diagnostic marker, prostatitis, urinary asparagine-linked glycosylation     

Serum total PSA and free PSA in breast tumors

Now a days measurement of molecular forms of PSA has gained importance in clinical practice. Several studies have demonstrated the production of PSA in female tissues, such as breast. The present piece of work has been undertaken with an objective to estimate the relative proportion of the molecular forms of PSA in serum along with serum testosterone in benign and malignant breast tumor cases and to analyze their association with the severity of the disease process 34 malignant and 26 benign breast disease cases along with 33 healthy controls of same age group were enrolled in this study for evaluation. Serum testosterone was measured by ELISA, whereas serum total PSA (TPSA) and free PSA (FPSA) were estimated by electrochemiluminescence immunoassay. A significant rise of fasting plasma glucose along with prominent dyslipidemia was observed in breast tumor cases. Marked rise in serum testosterone as well as TPSA and FPSA was documented in both benign and malignant breast tumor cases. Serum testosterone revealed a significant positive association with both TPSA and FPSA pointing towards an etiological association between them. However, surgical removal of tumor mass resulted in a marked decline of presurgical value of both TPSA and FPSA with a non-significant fall in serum testosterone revealing tumor tissue as the source of FPSA and TPSA. Thus, estimation of PSA provides prognostic information that may assist in future treatment.     

Diagnostic Role of Tumour Markers CEA, CA15-3, CA19-9 and CA125 in Lung Cancer

The aim of this study was to assess the diagnostic yield of the tumour markers carcinoembryonic antigen, carbohydrate antigen 15-3, carbohydrate antigen 19-9 and carbohydrate antigen 125, in serum and bronchoalveolar lavage fluid in a group of patients with bronchogenic carcinoma. Serum and bronchoalveolar lavage fluid samples were collected in a group of 90 patients with benign or malignant pulmonary diseases. After appropriate processing, tumour markers were determined by enzyme immunoassay. The diagnostic yields (sensitivity, specificity and predictive values) in each environment (serum and bronchoalveolar lavage fluid) were obtained by using "Receivers operating characteristic" curve. Determined individually, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 125, showed the greatest diagnostic accuracy in bronchoalveolar lavage fluid. Carbohydrate antigen 15-3 did so in serum. Carcinoembryonic antigen was the most relevant marker in bronchoalveolar lavage fluid. For the factors evaluated in this study, determination of carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 125 in bronchoalveolar lavage fluid were clinically more useful markers in comparison with serum, although the latter may also be helpful in certain situations. Although there is no specific tumour marker for lung cancer, the combination of several can be used to diagnose most patients with lung cancer and also to rule out false positive and negative cases.     

Significance of tumor markers in lung cancer

The objective was to test the utility of the cytokeratins CYFRA 21-1, tissue polypeptide specific antigen (TPS), Neuron specific enolase (NSE) and Carcino Embryonic antigen (CEA) in patients with lung cancer and in the pleural fluid of the patients with lung cancer and also the predicting ability of these tumor markers with respect to the histological types [including non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] and pathological stages. 40 normal subjects and 222 cases of histological proven lung cancer were studied. The findings suggest that TPS and CYFRA 21-1, are useful serum markers for the diagnosis of NSCLC and NSE seems to be useful tumor marker for monitoring course of patients especially SCLC. The combined use of these cytokeratin markers TPS and CYFRA 21-1 may provide additional information for prognosis.