Sung-Goo Chang

Salvage prostatectomy for recurrent prostate cancer after external beam radiotherapy (EBRT) has resulted in positive outcomes; however, it is technically challenging and is associated with a number of risks. When a patient exhibits recurrent prostate cancer following definitive EBRT and presents with comorbidities meaning that they cannot receive a prostatectomy, it is difficult to treat due to the numerous limitations of current salvage therapies. In the present study, two cases of salvage reirradiation using helical tomotherapy for locally recurrent prostate cancer following definitive EBRT are presented. The two patients received EBRT without severe complications. Local recurrence was confirmed by serum levels of prostate-specific antigen, repeat prostate biopsy, prostate magnetic resonance imaging and a bone scan. Salvage reirradiation using helical tomotherapy was performed and resulted in promising outcomes without any complications. In conclusion, helical tomotherapy can be a safe and effective salvage treatment modality for locally recurrent prostate cancer following definitive EBRT.

DNA hypomethylation was the initial epigenetic abnormality recognized in human malignancy. In the present study, the GoldenGate high‑throughput genotyping assay was adapted to determine the methylation state of 1,505 specific CpG sites in 807 cancer‑related genes. The methylation results revealed that CC chemokine receptor 5 (CCR5) was hypomethylated (mean β‑value difference, ‑0.21) in clear cell renal cell carcinoma (CCRCC) tissue. Tissue samples from 61 CCRCC cases were used for immunohistochemical staining, and patients with low CCR5 expression (n=44) were compared with those with high CCR5 expression (n=17). Tumor (T) stage was significantly lower in the low expression group compared with the high expression group (P=0.047). The Fuhrman grade of patients in the low expression group was significantly lower than that of patients in the high expression group (P=0.044). Whilst the node (N) and metastasis (M) stages of the CCR5 low expression group appeared to be lower compared with those of the CCR5 high expression group; this difference was not statistically significant (N stage, P=0.632; M stage, P=0.896). Additionally, patients in the low expression group had lower risks of postoperative tumor recurrence (P=0.110) and mortality from CCRCC (P=0.159) compared with those in the high expression group, however, this was also without statistical significance. The results indicate that CCR5 hypomethylation is associated with cancer tissue to a greater extent than normal tissue. Although the biological function of CCR5 in CCRCC remains to be established, low CCR5 expression is associated with low T stage and low Fuhrman grade in these patients.

DNA hypermethylation plays a major role in the regulation of gene expression in differentiation, development and diseases. The DNA mismatch repair system, which includes Mut‑S‑Homologon‑2 (MSH2) protein, is essential to maintain the stability of the genome during repeated duplication. This study aimed to investigate tumoral MSH2 immunohistochemical expression in clear cell renal cell carcinoma (RCC), and the associations between tumoral MSH2 immunohistochemical expression and clinicopathological parameters. Previously, we reported a high‑throughput method for analyzing the methylation status of 807 preselected genes; Illumina's GoldenGate Methylation Cancer Panel I microarray. The MSH2 gene was identified to be hypermethylated in cancer tissue compared with normal tissue. From January 2000 to December 2012, 129 clear cell RCC cases (median age, 61 years) were included in the immunohistochemical analysis of the present study. Patients were divided according to MSH2 expression status (MSH2‑negative, n=53; MSH2‑positive, n=76). T stage was significantly higher in the MSH2‑negative group than in the MSH2 positive‑group (P=0.021). There was no significant difference in terms of N stage, M stage and Fuhrman's nuclear grade between the MSH2‑negative and MSH2‑positive group (N stage, P=0.072; M stage, P=0.759; Fuhrman's nuclear grade, P=0118). The MSH2‑negative group showed decreased rates of recurrence‑free survival, progression‑free survival and overall survival, without statistically significant results (P=0.232, P=0.268 and P=0.311, respectively). MSH2 protein expression may be a useful marker for predicting TNM stage and prognosis and, thus, MSH2 may be a prognostic factor in clear cell RCC.

Son HS, et al. Korean J Urol. 2013 Nov;54(11):744-749. http://dx.doi.org/10.4111/kju.2013.54.11.744

DNA hypomethylation is associated with carcinogenesis due to its involvement in cancer initiation and progression. In this study we analyzed the hypomethylation status of candidate genes in clear cell renal cell carcinoma (CCRCC) using a large-scale, high-throughput DNA methylation profiling technique. Results revealed that hypomethylated interleukin 8 (IL8) gene was the most prominent of the candidate genes, with a beta value difference of 0.406 (cancer tissue mean beta value, 0.346; normal tissue mean beta value, 0.752). Validation results using sequencing analysis demonstrated that the methylation rate was 2.4% in cancer tissue and 14.7% in normal tissue, whilst the non-methylation rate was 82.9% in cancer tissue and 52.9% in normal tissue. However, the hypomethylation status of IL8 had no significant relationship with Fuhrman's nuclear grade, tumor node metastasis (TNM) stage or survival (P>0.05). We revealed that the IL8 gene is maximally hypomethylated in cancer tissue compared to normal tissue.

Intravesical bacillus Calmette-Guérin (BCG) therapy is the standard prophylaxis for recurrence of non-muscle-invasive bladder cancer (NMIBC). The aim of this study was to confirm the recurrence- and progression-preventing efficacy and safety of 12 times monthly BCG maintenance therapy for NMIBC. This study included 126 patients diagnosed with Ta, T1 and carcinoma in situ bladder cancer between January 2000 and December 2009. Thirty-four patients in the no maintenance group received a single 6-week course of intravesical immunotherapy after transurethral resection of the bladder tumor (TUR-BT). Ninety-two patients in the maintenance group received a 12-month course after a single 6-week course of intravesical immunotherapy. Recurrence, progression and side effects were assessed. End-points were recurrence-free survival (RFS), progression-free survival (PFS) and disease-specific survival (DSS). The estimated median RFS was 87 months (95% CI 53.0–120.9) in the maintenance group and 48 months (95% CI 0–96.8) in the no maintenance group (log-rank test; P=0.002). The 2-year cumulative RFS rates were 77.3% in the maintenance group and 52.6% in the no maintenance group. Median PFS and DSS were not estimable in both groups. The 2-year cumulative PFS rates were 91.1% in the maintenance group and 80.5% in the no maintenance group (log-rank test; P=0.178). The 2-year cumulative DSS rates were 97.7% in the maintenance group and 91.4% in the no maintenance group (log-rank test; P=0.111). The overall side effects were 40.2% in the maintenance group and 44.1% in the no maintenance group. Monthly maintenance immunotherapy appears to increase RFS rates in high-risk NMIBC. Further study is required to evaluate the efficacy of BCG monthly maintenence for increasing the PFS rate.

Yoo KH, et al. J Korean Med Sci. 2011 May;26(5):659-664. http://dx.doi.org/10.3346/jkms.2011.26.5.659

The high‐throughput method using microarray is an easy and fast way to analyze the methylation status of hundreds of preselected genes and to screen them for signatures in methylation. The aim of our study is to detect hypermethylated genes and to analyze the association between methylation status and clinicopathological parameters of clear cell renal cell carcinoma. The genetic substrate included 62 cancer tissues and 62 matched adjacent normal kidney tissues. We adapted the GoldenGate genotyping assay to determine the methylation state of 1505 specific CpG sites in 807 genes. We identified two genes (HOXA5 and MSH2) with β‐value differences of more than 0.3 between cancer and normal tissues. The high methylation group in HOXA5 had high Fuhrman's nuclear grade (P= 0.041). Other data in HOXA5 and MSH2 were not significant with methylation status (P > 0.05). Survival curve of the high methylation group in HOXA5 was slightly lower than that of the low methylation group. However, the statistical significances of overall survival in HOXA5 and MSH2 were low (P > 0.05). We report the hypermethylation of two genes in clear cell renal cell carcinoma. The data we obtained could provide the basis for a diagnostic test pathological assessment, or prognosis in clear cell renal cell carcinoma.

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