ODF4, MAGEA3, and MAGEB4: potential biomarkers in patients with transitional cell carcinoma

Background: This study aimed to evaluate the diagnostic value of outer dense fiber 4 [ODF4], melanoma associated antigen A3 [MAGEA3], and MAGEAB4 mRNAs in transitional cell carcinoma [TCC], using a small amount of cell reverse transcriptase-polymerase chain reaction [RT-PCR] on urinary exfoliated cells

Methods: We recruited a total of 105 suspected TCC patients and 54 sex- and age-matched non-TCC controls. The candidates' genetic expression patterns were investigated with RT-PCR, while reverse transcription quantitative PCR was applied to quantify and compare each mRNA level between cases and control groups

Results: The sensitivity of ODF4, MAGEA3, and MAGEAB4 RT-PCR was 54.8%, 63%, and 53.4%, whereas the specificity was 73.7%, 86%, and 94.7%, respectively. Combining ODF4, MAGEA3, and MAGEAB4 RT-PCR offered a relatively higher sensitivity [83.6%]

Conclusion: RT-PCR with ODF4, MAGEA3, and MAGEAB4 on urinary exfoliated cells could provide clinicians with a promising method to improve TCC diagnosis, especially in the case of gross hematuria and catheterization. The method used here is non-invasive, simple and convenient, and unlike cytology, it does not rely directly on expert professional opinions. These features can be of particular importance to the management of TCC patients in whom regular and lifelong surveillance is required

PKD2 mutation in an Iranian autosomal dominant polycystic kidney disease family with misleading linkage analysis data

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder caused by mutation in 2 genes PKD1 and PKD2. Thus far, no mutation is identified in approximately 10% of ADPKD families, which can suggest further locus heterogeneity. Owing to the complexity of direct mutation detection, linkage analysis can initially identify the responsible gene in appropriate affected families. Here, we evaluated an Iranian ADPKD family apparently unlinked to both PKD1 and PKD2 genes. This is one of the pioneer studies in genetic analysis of ADPKD in Iranian population. METHODS: Linkage reanalysis was performed by regenotyping of flanking microsatellite markers in 8 individuals of the ADPKD family. Direct mutation analysis was performed by Sanger sequencing. RESULTS: Mutation analysis revealed a pathogenic mutation (c.1094+1G>A) in the PKD2 gene in the proband. Analyzing 2 healthy and 4 clinically affected members confirmed the correct segregation of the mutation within the family and also ruled out the disease in 1 suspected individual. Misinterpretation of the linkage data was due to the occurrence of 1 crossing over between the PKD2 intragenic and the nearest downstream marker (D4S2929). Homozygosity of upstream markers caused the recombination indistinguishable. CONCLUSION: Although analysis of additive informative polymorphic markers can overcome the misleading haplotype data, it is limited because of the lack of other highly polymorphic microsatellite markers closer to the gene. Direct mutation screening can identify the causative mutation in the apparently unlinked pedigree; moreover, it is the only approach to achieve the confirmed diagnosis in individuals with equivocal imaging results.

[Sensitivity and specificity of serum PSA, free to total PSA ratio and transrectal ultrasonography findings in prostate cancer detection]

We conducted this study to evaluate and compare the sensitivity and specificity of various para-clinic parameters in detecting prostate cancer. In this cross-sectional study, 220 patients who underwent prostate biopsies for either high serum PSA level or abnormal digital rectal examination. Sensitivity and specificity of serum PSA, free to total PSA ratio and transrectal ultrasonography findings were calculated. Based on the pathological findings in 220 cases, 25% were diagnosed with prostate cancer. The mean age of patients with prostate cancer was 69.11 +/- 8.6 years. Mean serum PSA level among prostate cancer patients was significantly higher than in other patients [19.5 +/- 17.5 ng/dl vs. 10.5 +/- 8.1 ng/dl] [P=0.003]. The sensitivity and specificity of PSA for detecting prostate cancer, considering cut-off value of 4 ng/dl, was 92% and 2%, respectively. Free to total PSA ratio with cut-off value of 10% revealed 82% sensitivity and 17% specificity. Moreover, hypoechoic lesions detected by transrectal ultrasound had a sensitivity and specificity of 34% and 93%, respectively. Combination of different PSA related parameters with tranrectal ultrasound findings might increase sensitivity and specificity in detecting prostate cancer and reduce unnecessary biopsies

Prevalence of lymph node metastasis in radical prostatectomy; a retrospective and multicenter study in Iran

Lymph node [LN] metastasis is considered an important prognostic factor in patients with prostate cancer. The aim of this study was to determine the rate of LN metastasis among an Iranian population who underwent radical prostatectomy [RP] with pelvic LN dissection [PLND]. In a retrospective review of medical records, 450 RP cases were included and the data on LN metastasis were extracted from surgical pathology reports. Overall, 4.7% of the patients had LN metastasis. The rate of surgical stage T3 [50% vs. 13.5%; P=0.021] and pathological Gleason score [3]7 [82.4% vs. 48.8%; P=0.002] was significantly higher among LN-positive patients. All patients with LN metastasis had a serum prostate specific antigen level >4 ng/ml. The diagnosis of prostate cancer is in an acceptable, but not ideal, stage of the disease; this may be due to screening examinations and tests

Prostate-specific antigen doubling time as a predictor of Gleason grade in prostate cancer

Our aim was to evaluate the value of serum prostate-specific antigen doubling time [PSADT] to differentiate patients with high-grade prostate cancer who require more aggressive therapy from those with low-grade cancer. Of 460 patients with extended 12-core transrectal ultrasonography-guided biopsy of the prostate, 59 with confirmed prostate cancer were selected. They had not received any previous treatment for prostate cancer and had at least 2 consecutive serum PSA tests with a rising trend. The PSADT was calculated in patients with 2 serum PSA levels measured with an interval more than 3 months. Of 59 patients with prostate cancer, 35 [59.3%] had low-grade and 24 [40.7%] had high-grade tumors. There was no difference in age between the two groups. The median PSADT in patients with high-grade tumors were 12.70 months [range, 0.7 to 44.8 months] and 25.00 months [range, 1.65 to 41.2 months; P=.001]. A total of 21 patients with high-grade tumors [87.5%] had a PSADT less than 12 months, while only 9 of those with low-grade tumors [25.7%] had a PSADT less than 12 months. A PSADT with low-grade tumors [25.7%] had a PSADT less than 12 months. A PSADT cutoff of 12 months provided a sensitivity of 74% and a specificity of 87% for differentiation of high-grade from low-grade cancers. We concluded that men with a short PSADT [<12 months] were at a higher risk of harboring a high-grade prostate cancer. Our data suggests PSADT can identify patients with high-grade tumors who require more aggressive therapy

Frequency and outcome of metaplasia in needle biopsies of prostate and its relation with clinical findings

Metaplasia is a reversible change in which one adult cell type is replaced by another adult cell type. Our aim was to determine the frequency and outcome of metaplasia in specimens from needle biopsies of the prostate and its relation with clinical findings. Among 1566 prostate specimens referred to 2 pathology centers of Tehran, we studied on cases with a diagnosis of metaplasia, during a 2-year period. The clinical and laboratory data of the patients with metaplasia were collected, and they were followed-up for 2 years. Age, serum total and free prostate-specific antigen levels, ultrasonography findings, and results of digital rectal examination were recorded at baseline and the follow-up period. Ten prostate specimens [0.6%] had metaplasia, of which 6 were transitional and 4 were squamous metaplasia. Serum total PSA levels ranged from 0.7 ng/mL to 14.5 ng/mL, and free PSA levels ranged from 0.1 ng/mL to 1.3 ng/mL in the patients with metaplasia. None of the patients developed carcinoma of the prostate during the 2-year follow-up, and no significant changes were seen in the follow-up sutides. Metaplasia of the prostate are often associated with BPH. Clinical findings on DRE and TRUS resemble those found in benign lesions of the prostate, such as BPH. We found no sign of developing of this benign lesion, malignant lesions, such as squamous cell carcinoma or urothelial transitional cell carcinoma, should also be taken into consideration

Extensive surgical management for renal tumors with inferior vena cava thrombus

The aim of this study was to evaluate the outcome in patients with renal cell carcinoma [RCC] and the inferior vena cava [IVC] or the right atrium tumor thrombus that were treated with radical nephrectomy and thrombectomy. Eleven of a total of 105 patients who underwent radical nephrectomy due to RCC had tumor thrombus extended to the IVC and/or the right atrium. We evaluated the surgical techniques used and the perioperative mortality and morbidity in these patients. The median age of the patients was 47 years [range, 16 to 59 years]. They all underwent radical nephrectomy with cavotomy, tumor thrombus removal, and lymphadenectomy. Eight patients underwent extracorporeal circulation and hypothermic circulatory arrest; 2, temporary venovenous bypass by chevron incision and median sternotomy; and 1, only chevron incision with mobilization of the right lobe of the liver and cross-clamping proximal to the tumor thrombus and cavotomy. In 1 case, a solitary liver metastasis was excised and the patient died within 30 days postoperatively because of massive hemorrhage due to liver metastatectomy. Two patients had invasion to the IVC wall and 7 had pathological lymph node involvement. Four patients were tumor free [follow-up range, 9 to 18 months] and 7 died due to multiple metastases during the follow-up. This study supports the role of extensive surgical treatment as the best initial management of patients with renal cancer extended to the IVC only in highly selected cases