Circulating microRNA biomarkers in melanoma: tools and challenges in personalised medicine

Effective management of melanoma depends heavily on early diagnosis. When detected in early non-metastatic stages, melanoma is almost 100% curable by surgical resection, however when detected in late metastatic stages III and IV, 5-year survival rates drop to ~50% and 10–25%, respectively, due to limited efficacy of current treatment options. This presents a pressing need to identify biomarkers that can detect patients at high risk of recurrence and progression to metastatic disease, which will allow for early intervention and survival benefit. Accumulating evidence over the past few decades has highlighted the potential use of circulating molecular biomarkers for melanoma diagnosis and prognosis, including lactate dehydrogenase (LDH), S100 calcium-binding protein B (S100B) and circulating tumor DNA (ctDNA) fragments. Since 2010, circulating microRNAs (miRNAs) have been increasingly recognised as more robust non-invasive biomarkers for melanoma due to their structural stability under the harsh conditions of the blood and different conditions of sample processing and isolation. Several pre-analytical and analytical variables challenge the accurate quantification of relative miRNA levels between serum samples or plasma samples, leading to conflicting findings between studies on circulating miRNA biomarkers for melanoma. In this review, we provide a critical summary of the circulating miRNA biomarkers for melanoma published to date

The significance of the Van Nuys prognostic index in the management of ductal carcinoma in situ

<p>Abstract</p> <p>Background</p> <p>Debate regarding the benefit of radiotherapy after local excision of ductal carcinoma <it>in situ </it>(DCIS) continues. The Van Nuys Prognostic Index (VNPI) is thought to be a useful aid in deciding which patients are at increased risk of local recurrence and who may benefit from adjuvant radiotherapy (RT). Recently published interim data from the Sloane project has showed that the VNPI score did significantly affect the chances of getting planned radiotherapy in the UK, suggesting that British clinicians may already be using this scoring system to assist in decision making. This paper independently assesses the prognostic validity of the VNPI in a British population.</p> <p>Patients and methods</p> <p>A retrospective review was conducted of all patients (n = 215) who underwent breast conserving surgery for DCIS at a single institution between 1997 – 2006. No patients included in the study received additional radiotherapy or hormonal treatment. Kaplan Meier survival curves were calculated, to determine disease free survival, for the total sample and a series of univariate analyses were performed to examine the value of various prognostic factors including the VNPI. The log-rank test was used to determine statistical significance of differential survival rates. Multivariate Cox regression analysis was performed to analyze the significance of the individual components of the VNPI. All analyses were conducted using SPSS software, version 14.5.</p> <p>Results</p> <p>The mean follow-up period was 53 months (range 12–97, SD19.9). Ninety five tumours were high grade (44%) and 84 tumours exhibited comedo necrosis (39%). The closest mean initial excision margin was 2.4 mm (range 0–22 mm, standard deviation 2.8) and a total of 72 tumours (33%) underwent further re-excision. The observed and the actuarial 8 year disease-free survival rates in this study were 91% and 83% respectively. The VNPI score and the presence of comedo necrosis were the only statistically significant prognostic indicators (P < 0.05).</p> <p>Conclusion</p> <p>This follow-up study of 215 patients with DCIS treated with local excision and observation alone is one of the largest series in which rates of recurrence are unaffected by radiation therapy, hormone manipulation or chemotherapy. It has afforded us the opportunity to assess the prognostic impact of patient and tumour characteristics free of any potentially confounding treatment related influences. The results suggest that the VNPI can be used to identify a subset of patients who are at risk of local recurrence and who may potentially benefit from RT.</p