Immunocytochemical detection of ERG expression in exfoliated urinary cells identifies with high specificity patients with prostate cancer.

OBJECTIVES: To evaluate the immunocytochemical detection of ERG protein in exfoliated cells as a means of identifying patients with prostate cancer (PCa) before prostate biopsy. MATERIALS AND METHODS: Urine samples (30 mL) were collected after digital rectal examination (DRE) from 159 patients with an elevated age-specific prostate-specific antigen (PSA) and/or an abnormal DRE who underwent prostate biopsy. In all cases, exfoliated urinary cells from half of the urine sample underwent immunocytochemical assessment for ERG protein expression. Exfoliated cells in the remaining half underwent assessment of TMPRSS2:ERG status using either nested reverse-transcriptase (RT)-PCR (151 cases) or fluorescence in situ hybridization (FISH; eight cases). Corresponding tissue samples were evaluated using FISH to determine chromosomal gene fusion tissue status and immunohistochemistry (IHC) to determine ERG protein expression. Results were correlated with clinicopathological variables. RESULTS: The sensitivity and specificity of urinary ERG immunocytochemistry (ICC) for PCa were 22.7 and 100%, respectively. ERG ICC results correlated with advanced tumour grade, stage and higher serum PSA. In comparison, urine TMPRSS2:ERG transcript analysis had 27% sensitivity and 98% specificity for PCa detection. On tissue IHC, ERG staining was highly specific for PCa. In all, 52% of cancers harboured foci of ERG staining; however, only 46% of cancers that were found to have ERG overexpression were positive on urine ICC. The ERG ICC results showed strong concordance with urinary RT-PCR and FISH, and tissue IHC and FISH. CONCLUSION: This is the first study to show that cytological gene fusion detection using ICC is feasible and identifies patients with adverse disease markers. ERG ICC was highly specific, but this technique was less sensitive than RT-PCR.

Could triaging family history of cancer during palliative care enable earlier genetic counseling intervention?

BACKGROUND: Patients are commonly referred to cancer genetics services when all affected family members are deceased. This makes genetic testing and risk assessment more difficult, reducing the benefit from screening and prophylactic treatment. METHODS: Observational, retrospective, cohort study of 508 randomly selected patients referred to a regional cancer genetics unit, using review of case notes to explore whether a simple clinical "3, 2, 1" family history rule could have been used to improve timely and appropriate referrals for genetic assessment. The 3, 2, 1 criteria are: three affected relatives with the same/associated cancers, across two generations, with at least one person affected age <50 years. RESULTS: Most (71% [362]) genetic risk assessment referrals were in unaffected individuals and 22% (80) of these were referred after all affected family members had died, including 24% (19) who lost their last remaining affected relative in the previous year. Most (59% [301]) referrals met all 3, 2, 1 criteria, and 67% of these could have been made earlier in clinical practice. A further 23% (115) met two of the three criteria. CONCLUSION: Using a simple "3, 2, 1" family rule in cancer care and particularly in palliative care could enable earlier cancer genetic risk assessment for unaffected relatives, improving the potential to benefit from targeted screening and intervention.

Association between single nucleotide polymorphisms in the DNA repair gene LIG3 and acute adverse skin reactions following radiotherapy.

Many genes have been associated with radiotherapy toxicity, but most have only been found in a single study. Using our cohort of 480 breast cancer patients, we provide replicated evidence that a polymorphism near the LIG3 gene is associated with acute skin toxicity following radiotherapy.