Evaluation of some biochemical markers of cancer prostate

The incidence of Cancer Prostate [PCa] has increased dramatically during the last 10-15 years many strategies have been proposed to enhance the ability of PSA in differentiation of PCa from BPH and f/t PSA was one of those strategies that were reported to improve the diagnostic accuracy of PSA. Of these markers we evaluated prostatic specific antigen [PSA], Neurone specific enolase [NSE], Tissue polypeptide specific antigen [TPS] and Scatter factor [SF], also known as hepatocyte growth factor [HGF]. The present study aimed at evaluating the measurement of serum levels of NSE, TPS and HGF in combination with PSA and I7t PSA in cancer prostate patients to assess their diagnostic and prognostic value in such patients. The study was conducted on 72 patients complaining of obstructive symptoms as frequency and urgency. The first group comprised 26 subjects diagnosed as BPH, the second group consisted of 21 subjects diagnosed as localized PCa and the third group consisted of 25 subjects diagnosed as metastatic PCa. The latter group was further divided according to Gleason score into moderately differentiated [n=13] and poorly differentiated adenocarcinoma [n=12]. All patients were subjected to transrectal ultrasonography [TRUS] and core needle biopsy from the prostate for histopathological examination, and assay of serum tPSA, fPSA measured by chemiluminescent immunometric assay, NSE using electrochemiluminescence immunometric assay, TPS [1RMA] and HGF [ELISA]. Median values of tPSA was significantly higher in metastatic PCa [group III] compared to localized PCa [group II] and BPH patients [group I] [68, 7.0, 2.0ng/ml respectively P<0.001], f/t PSA was significantly lower in PCa patients [group II, group III] compared to BPH patients [0.13, 0.14,0.2 respectively, P=0.004], TPS was significantly higher in metastatic PCa [140U/L] compared to group I and group II [77,65U/L, respectively P=0.004] and HGF was significantly highest in metastatic PCa patients compared to group I and group II [2270, 2132, 1789pg/ml, respectively, P=0.047]. A statistical significant positive correlation was found in the malignant group between PSA and HGF and between [TPS] on one hand and [NSE and HGF] on the other hand. Simultaneous assay of PSA and HGF yielded a sensitivity of 96% in discriminating between BPH from malignant prostate compared to 91% for HGF and 93% for PSA alone. Higher NSE levels were found in higher stage and higher grade PCa. On evaluating the metastatic PCa group, it was found that poor PSA progression free survival [shorter time to androgen responsiveness] is associated with high NSE levels, and with poorly differentiated adenocarcinoma [high Gleason score 8-10]. The value of tPSA in diagnosing cancer prostate is still of uncertainty, however, it is better to be combined with f/tPSA assay. The f/tPSA is useful in discriminating between BPH and PCa especially in the early stage [localized PCa] and thus allowing early intervention and treatment. A cutoff value of 0.24 for f/tPSA is recommended as it detects 87% of cancer cases and at the same time avoids 39% of unnecessary prostate biopsy. Moreover, combining PSA and HGF was more accurate in discriminating between BPH and malignant prostate than either marker alone. HGF alone is of prognostic significance especially in the presence of metastates and correlates well with the stage and grade of cancer prostate. An increase in TPS signifies clinical progression even if PSA is found to remain normal. Thus it is of value in overcoming the relative insensitivity of PSA in some of hormonally treated patients. High NSE levels are of prognostic significance in patients with metastatic PCa treated with androgen withdrawal therapy

Genetic polymorphisms of DNA repair gene XRCC1 and susceptibility to acute leukemia

Defective DNA repair has been reported to be a risk factor for various malignancies. Polymorphisms of DNA repair genes could alter protein structure and may impair DNA repair capacity. Genetic polymorphisms of XRCC1 gene could lead to defective base excision repair [BER] pathway resulting in impaired DNA repair capacity and increased risk of acute leukemia. To determine the possible effect of XRCC1 gene polymorphisms 194Arg to Trp and 399Arg to Gin on the risk of development of acute leukemia in a group of Egyptian patients. The study was also extended to evaluate the association between these polymorphisms and disease outcome. Polymorphisms of XRCC1 codon 194 [Arg to Trp] and codon 399 [Arg to Gin] were genotyped in 35 patients with acute lymphoblastic leukemia [ALL], 35 patients with acute myeloid leukemia [AML] and 70 healthy controls using polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] method. Individuals with heterozygous XRCC1 194 Arg/Trp variant demonstrated a significant increased risk of AML than controls [Odds Ratio [OR] 3.5, 95% confidence interval [CI], 1.3-9.5]. The frequency of homozygous XRCC1 399 Gin/Gin variant was statistically higher in ALL patients than controls [OR 3.69, 95% CI, 1.19-11.4]. Stratification for sex with regard to codon 194Trp carriers showed that males had 3.2-fold increased risk of ALL than females with borderline significance. In case of codon 399Gln polymorphism, a highly significant risk of ALL among females was observed with 7.5-fold increased risk. The frequency of XRCC1 haplotype A [399Gln carriers and 194Trp carriers] was significantly higher in both ALL and AML patients than controls [OR5.2, 95% CI, 1.6-16.7, p-value <0.01 for ALL] [OR 3.2, 95% CI, 0.9-11.1, p-value=0.055 for AML]. The polymorphic variant of XRCC1 194Trp has a significant unfavorable effect on disease outcome among ALL and AML patients [p-value 0.002 and 0.05 respectively]. Acute lymophoblastic leukemia patients carrying the 399Gln allele experienced a significant unfavorable outcome than ALL patients carrying the wild-type allele [p-value<0.01]. An increased risk of AML among carriers of XRCC1 194Trp and an increased risk of ALL among patients with XRCC1 399Gln variant genotypes were observed. Combined presence of XRCC1 194Trp and 399Gln variants [haplotype A] had significantly higher risk of both ALL and AML. The polymorphic variants of XRCC1 codons 194 and 399 had significant unfavorable effect on disease outcome of both AML and ALL