Expression profile of MAGI2 gene as a novel biomarker in combination with major deregulated genes in prostate cancer.

Complex molecular changes that occur during prostate cancer (PCa) progression have been described recently. Whole genome sequencing of primary PCa samples has identified recurrent gene deletions and rearrangements in PCa. Specifically, these molecular events disrupt the gene loci of phosphatase and tensin homolog (PTEN) and membrane-associated guanylate kinase inverted-2 (MAGI2). In the present study, we analyzed the expression profile of MAGI2 gene in a cohort of clinical PCa (n = 45) and benign prostatic hyperplasia (BPH) samples (n = 36) as well as three PCa cell lines. We also studied the expression of PCa-related genes, including PTEN, NKX3.1, SPINK1, DD3, AMACR, ERG, and TMPRSS2-ERG fusion in the same samples. The expression of MAGI2 mRNA was significantly down-regulated in PC3, LNCaP and DU-145 PCa cell lines (p = 0.000), and also in clinical tumor samples (Relative expression = 0.307, p = 0.002, [95 % CI 0.002-12.08]). The expression of PTEN, NKX3.1, SPINK1, DD3, and AMACR genes was significantly deregulated in prostate tumor samples (p range 0.000-0.044). A significant correlation was observed between MAGI2 and NKX3.1 expression in tumor samples (p = 0.006). Furthermore, the inclusion of MAGI2 in the gene panel improved the accuracy for discrimination between PCa and BPH samples with the sensitivity and specificity of 0.88 [CI 0.76-0.95] and 0.83 [CI 0.68-0.92], respectively. The data presented here suggest that MAGI2 gene can be considered as a novel component of gene signatures for the detection of PCa.

Is There a Role for Genetic Information in Risk Assessment and Decision Making in Prostate Cancer?

OBJECTIVES: Prostate cancer is a neoplasm with a variable natural history and clinical behavior. There is much debate on the use of inherited genetic information in clinical application including risk assessment and treatment decisions. This study was performed to evaluate the relationship between clinical parameters of prostate cancer (PSA, Gleason score, and metastasis) and expression of NKX3.1, AMACR, TMPRSS2-ERG, ERG, and SPINK1 genes. METHODS: Newly diagnosed cases of prostate cancer were selected for this study. Thirty four tissue samples were obtained via open radical prostatectomy and 9 samples were obtained via needle biopsy. Each tissue sample was sectioned into two parts, one used for detection of malignant changes and Gleason score determination, and the other immersed in RNA later solution (Qiagen). The expression of NKX3.1, AMACR, TMPRSS2-ERG, ERG, and SPINK1 genes were assessed by real-time PCR assay. Correlation between expression of each gene and PSA level, Gleason score, and presence of metastasis were examined. RESULTS: A total number of 43 specimens were studied, from which 9 were obtained from patients with metastatic prostate cancer. The expression of five examined genes had no correlation with PSA level and Gleason score. The expression of AMACR decreased in metastatic prostate cancer (P = 0.02). The expression of other genes showed no difference between metastatic and non-metastatic tumors (P > 0.1). CONCLUSIONS: Genetic information combined with clinical data can be useful in risk assessment and treatment planning. Based on the results of the current study, the decreased expression of AMACR was a sign of poor prognosis.

Postchemotherapy Retroperitoneal Lymph Node Dissection in Patients With Nonseminomatous Testicular Cancer: A Single Center Experiences.

BACKGROUND: Testicular cancer accounts for about 1 - 1.5% of all malignancies in men. Radical orchiectomy is curative in 75% of patients with stage I disease, but advance stage with retroperitoneal lymph node involvement needs chemotherapy. All patients who have residual masses ≥ 1 cm after chemotherapy should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). OBJECTIVES: Treatment of advanced nonseminomatous testicular cancer is usually a combination of chemotherapy and surgery. We described our experience about postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in our center. PATIENTS AND METHODS: In a retrospective cross-sectional study between 2006 and 2011, patients with a history of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in Imam Khomeini hospital were evaluated. All patients had normal postchemotherapy serum tumor markers and primary nonseminomatous cancer. We reviewed retrospectively clinical, pathological, and surgical parameters associated with PC-RPLND in our center. RESULTS: Twenty-one patients underwent bilateral PC-RPLND. Mean age was 26.3 years (ranged 16 - 47). Mean size of retroperitoneal mass after chemotherapy was 7.6 cm. Mean operative time was 198 minutes (120 - 246 minutes). Mean follow-up time was 38.6 months. Pathologic review showed presence of fibrosis/necrosis, viable germ cell tumor and teratoma in 8 (38.1%), 10 (47.6%) and 3 (14.28%) patients, respectively. One patient in postoperative period of surgery and three patients in two first years after surgery were expired. Of 17 alive patients, only two (11.8%) had not retrograde ejaculation. CONCLUSIONS: PC-RPLND is one the major operations in the field of urology, which is associated with significant adjunctive surgeries. In appropriate cases, PC-RPLND was associated with good cancer specific survival in tertiary oncology center.