The role of secreted frizzled-related protein 2 expression in prostate cancer

AIMS: Improved prostate cancer (PCa)-specific biomarkers are urgently required to distinguish between indolent and aggressive disease, in order to avoid overtreatment. In this study, we investigated the prostatic tissue expression of secreted frizzled-related protein (SFRP)-2.

METHODS AND RESULTS: Following immunohistochemical analysis on PCa tissue microarrays with samples from 216 patients, strong/moderate SFRP-2 expression was observed in epithelial cells of benign prostatic hyperplasia, and negative/weak SFRP-2 expression was observed in the majority of tumour epithelia. However, among Gleason grade 5 carcinomas, 40% showed strong/moderate SFRP-2 expression and 60% showed negative SFRP-2 expression in epithelial cells. Further microscopic evaluation of Gleason grade 5 tumours revealed different morphological patterns, corresponding with differential SFRP-2 expression. The first subgroup (referred to as Type A) appeared to have a morphologically solid growth pattern, whereas the second subgroup (referred to as Type B) appeared to have a more diffuse pattern. Furthermore, 100% (4/4) of Type A patients experienced biochemical recurrence, as compared with 0% (0/6) of Type B patients.

CONCLUSIONS: These results imply: (i) that there is a loss of SFRP-2 expression from benign to malignant prostate glands; and (ii) differential SFRP-2 expression among two possible subgroups of Gleason grade 5 tumours.

Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1

Breast cancer is a heterogeneous disease and several distinct subtypes exist based on differential gene expression patterns. Molecular apocrine tumours were recently identified as an additional subgroup, characterised as oestrogen receptor negative and androgen receptor positive (ER- AR+), but with an expression profile resembling ER+ luminal breast cancer. One possible explanation for the apparent incongruity is that ER gene expression programmes could be recapitulated by AR. Using a cell line model of ER- AR+ molecular apocrine tumours (termed MDA-MB-453 cells), we map global AR binding events and find a binding profile that is similar to ER binding in breast cancer cells. We find that AR binding is a near-perfect subset of FoxA1 binding regions, a level of concordance never previously seen with a nuclear receptor. AR functionality is dependent on FoxA1, since silencing of FoxA1 inhibits AR binding, expression of the majority of the molecular apocrine gene signature and growth cell growth. These findings show that AR binds and regulates ER cis-regulatory elements in molecular apocrine tumours, resulting in a transcriptional programme reminiscent of ER-mediated transcription in luminal breast cancers.

Localization of polymorphic N-acetyltransferase (NAT2) in tissues of inbred mice

Like humans, mice exhibit polymorphism in the N-acetylation of aromatic amines, many of which are toxic and/or carcinogenic. Mice have three N-acetyltransferase (Nat) genes, Nat1, Nat2 and Nat3, and Nat2 is known to be polymorphic. There is a dramatic difference in the acetylation of NAT2 substrates by blood from fast (C57BL/6J) compared with slow acetylator (A/J) mice. However, the acetylation of these substrates by liver cytosols from the two strains is very similar. In order to determine whether the expression of the NAT2 protein corresponded with the activities measured, a polyclonal antipeptide antisera was raised against the C-terminal decapeptide of NAT2 and characterized using recombinant murine NAT2 antigen. Enzyme-linked immunosorbent assays (ELISAs) demonstrated that the anti-NAT2 antiserum bound in a concentration-dependent fashion to recombinant NAT2. Immunochemical analysis of mouse liver cytosols from C57BL/6J or A/J livers indicated that the level of NAT2 protein expressed in the two strains was similar. Immunohistochemical staining of C57BL/6J liver with anti-NAT2 antiserum showed that NAT2 was expressed in hepatocytes throughout the liver although the intensity of staining in the perivenous (centrilobular) region was higher than that in the periportal region. NAT2 was also detected in epithelial cells in the lung, kidney, bladder, small intestine and skin as well as in erythrocytes and lymphocytes in the spleen and hair follicles and sebaceous glands in the skin. Characterization of the distribution of NAT2 will be of value in elucidating the role of polymorphic N-acetylation in protecting the organism from environmental insults as well as in endogenous metabolism.

Pre-Radiotherapy Dental Assessment of Head and Neck Oncology Patients: An Audit.

Objectives: Approximately 300 people are diagnosed with Head and Neck cancer annually in Northern Ireland. The management may include treatment by surgery or by chemotherapy and radiotherapy,
or a combination of modalities. Patients whose oral cavity, teeth, salivary glands and jaws that
will be affected by treatment, particularly radiotherapy should have a pre-treatment assessment. This should be done as early as possible to maximise the time available for dental management. However, this can be challenging owing to the complexities of cancer diagnosis, treatment planning and multidisciplinary management. At the Belfast Dental Hospital, a number of patients were referred post- radiotherapy with complications after not having received a pre-treatment assessment. The referrals for pre- treatment dental assessment were also late in patients’ multidisciplinary journey, limiting the time period
for dental input. The purpose of this audit was to examine the time period between dental assessment and commencement of radiotherapy and whether this was an adequate time frame for dental management. This audit will also examine the dental diseases present and the treatments required pre-radiotherapy. Methods: Data for this audit was collected over 4 months in 2012
by analysing the dental charts and referrals of new patients who were referred to and attended the dental head and neck oncology clinic. A standardised referral pro-forma was introduced from September 2013 to improve the referral process.
A re-audit was conducted over 4 months in 2014. Data was collected similarly as previous. The time period between dental assessment and commencement of radiotherapy was examined. The presence of dental disease and subsequent treatments required were also noted.
Results: 63 new patients were examined in the dental head and neck oncology clinic over 4 months in 2012. 48 (76.2%) were examined pre-radiotherapy. The average length of time between dental assessment and radiotherapy commencement was 11 days. A new standardised referral pro-forma was introduced in 2013. In the re-audit, 65 new patients were seen over 4 months in 2014.
60 (92.3%) patients were examined pre-radiotherapy. The average length of time between dental assessment and radiotherapy commencement was 18 days.
Conclusion: Given the high prevalence of pre-existing dental disease amongst head and neck cancer patients, prompt dental assessment and treatment is vital. Efforts aimed at improving the care pathway are on-going through the implementation of a mandatory referral pro-forma and a dedicated assessment clinic.

Increase in microbial contamination risk with compression of the lid margin in eyes having cataract surgery

Purpose: To assess the bacterial contamination risk in cataract surgery associated with mechanical compression of the lid margin immediately after sterilization of the ocular surface.

Setting: Department of Cataract, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Design: Prospective randomized controlled double-masked trial.

Methods: Patients with age-related cataract were randomly assigned to 1 of 2 groups. In Group A (153 eyes), the lid margin was compressed and scrubbed for 360 degrees 5 times with a dry sterile cotton-tipped applicator immediately after ocular sterilization and before povidone-iodine irrigation of the conjunctival sac. Group B (153 eyes) had identical sterilization but no lid scrubbing. Samples from the lid margin, liquid in the collecting bag, and aqueous humor were collected for bacterial culture. Primary outcome measures included the rate of positive bacterial culture for the above samples. The species of bacteria isolated were recorded.

Results: Group A and Group B each comprised 153 eyes. The positive rate of lid margin cultures was 54.24%. The positive rate of cultures for liquid in the collecting bag was significantly higher in Group A (23.53%) than in Group B (9.80%) (P=.001).The bacterial species cultured from the collecting bag in Group B were the same as those from the lid margin in Group A. The positive culture rate of aqueous humor in both groups was 0%.

Conclusion: Mechanical compression of the lid margin immediately before and during cataract surgery increased the risk for bacterial contamination of the surgical field, perhaps due to secretions from the lid margin glands.

Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.