Barry Powell

Revised U.K. guidelines for the management of cutaneous melanoma 2010.

These guidelines reflect the best published data available at the time the report was prepared. Caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations in this report. It may be necessary or even desirable to depart from the guidelines in the interests of specific patients and special circumstances. Just as adherence to the guidelines may not constitute defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent.

The development of optimal pathological assessment of sentinel lymph nodes for melanoma

1158 sentinel lymph nodes (SLNs), excised from patients with primary cutaneous melanoma, were assessed pathologically using histology with immunohistochemistry (IHC) on all nodes, and RT‐PCR for Mart‐1 and tyrosinase on 55 nodes. RT‐PCR was compared with the histology and IHC assessed on the same nodes. The evaluation of progressively more detailed protocols for histology and IHC modulated by the RT‐PCR results led to a procedure that consistently detects metastases in 34% of patients submitted to SLN biopsy for cutaneous melanomas with a vertical growth phase and a mean thickness of 2.02 mm (range 0.25, with regression, to 19 mm). As this technique is virtually free of false positives and produces only a marginally lower detection rate than RT‐PCR, which was subject to false positives of 7% in our study, it is suggested that this extended protocol should be the basis on which further evaluation of the place of RT‐PCR in SLN assessment takes place. The evolved protocol described here has been adopted by the EORTC as the standard procedure for pathological handling of sentinel lymph nodes for melanoma when SLN status is a criterion in their clinical trials or studies. Copyright

Sentinel node biopsy and standard of care for melanoma

An international panel was convened by the organizing committee of the International Sentinel Node (SN) Society (ISNS) at their meeting in Sydney, Australia, on February 21, 2008, to address questions about SN biopsy (SNB) for melanoma. The panelists subsequently wrote this consensus statement, based on their interpretation of current evidence, as a guide to clinical treatment of patients with clinically localized melanoma. The panel comprised a cross section of expert melanoma surgeons who have contributed data and leadership to investigations of SNB.

Revised UK guidelines for the management of cutaneous melanoma 2010

These guidelines for the management of cutaneous melanoma present an evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiology, diagnosis, investigation, and follow-up.

Gene Expression Profiling of Paraffin-Embedded Primary Melanoma Using the DASL Assay Identifies Increased Osteopontin Expression as Predictive of Reduced Relapse-Free Survival

Purpose: Gene expression studies in melanoma have been few because tumors are small and cryopreservation is rarely possible. The purpose of this study was to evaluate the Illumina DASL Array Human Cancer Panel for gene expression studies in formalin-fixed melanoma primary tumors and to identify prognostic biomarkers. Experimental Design: Primary tumors from two studies were sampled using a tissue microarray needle. Study 1: 254 tumors from a melanoma cohort recruited from 2000 to 2006. Study 2: 218 tumors from a case-control study of patients undergoing sentinel node biopsy. Results: RNA was obtained from 76 of blocks; 1.4 of samples failed analysis (transcripts from <250 of the 502 genes on the DASL chip detected). Increasing age of the block and increased melanin in the tumor were associated with reduced number of genes detected. The gene whose expression was most differentially expressed in association with relapse-free survival in study 1 was osteopontin (SPP1; P = 2.11 106) and supportive evidence for this was obtained in study 2 used as a validation set (P = 0.006; unadjusted data). Osteopontin level in study 1 remained a significant predictor of relapse-free survival when data were adjusted for age, sex, tumor site, and histologic predictors of relapse. Genes whose expression correlated most strongly with osteopontin were PBX1, BIRC5 (survivin), and HLF. Conclusion: Expression data were obtained from 74 of primary melanomas and provided confirmatory evidence that osteopontin expression is a prognostic biomarker. These results suggest that predictive biomarker studies may be possible using stored blocks from mature clinical trials. (Clin Cancer Res 2009;15(22):693946)

The correlation of regression in primary melanoma with sentinel lymph node status

Background: The significance of regression in primary melanoma has been disputed for many years. Some have suggested regression as a marker for poor prognosis while others have reported a negligible or even a favourable effect, on prognosis. Aim: To understand the significance of regression in melanoma and provide further information on whether patients should be subjected to sentinel lymph node biopsy (SLNB) on the basis of regression. Methods: 146 melanoma cases who had undergone SLNB were included in the study. The histological criteria for offering SLNB were melanoma >1 mm in thickness, Clark’s level IV or those with regression. Results: A statistically significant greater proportion of individuals without regression showed sentinel lymph node (SLN) positivity (p = 0.028) compared with those which do show regression. Metastatic disease correlated with growth phase of the primary lesion. All the node positive cases were in the vertical growth phase; none of the cases in radial growth phase and showing regression were associated with nodal metastasis (p = 0.029). 62 cases had melanomas with thickness <1 mm and were in radial growth phase, yet were offered SLNB because of regression. Of these, 44 showed features of regression and all were node negative. The remaining 16 cases of thin melanomas did not show regression; 2 of these had sentinel node metastasis. Conclusion: Results suggest that regression is usually a favourable process, particularly in thin melanomas and that metastasis in “thin melanomas showing regression” is real but rare. Variant vertical growth phase, mitoses and other prognostically significant variables may be more important predictors of metastatic potential in thin melanomas.

Patterns of Expression of DNA Repair Genes and Relapse From Melanoma

Purpose: To use gene expression profiling of formalin-fixed primary melanoma samples to detect expression patterns that are predictive of relapse and response to chemotherapy. Experimental Design: Gene expression profiles were identified in samples from two studies (472 tumors). Gene expression data for 502 cancer-related genes from these studies were combined for analysis. Results: Increased expression of DNA repair genes most strongly predicted relapse and was associated with thicker tumors. Increased expression of RAD51 was the most predictive of relapse-free survival in unadjusted analysis (hazard ratio, 2.98; P = 8.80 × 10−6). RAD52 (hazard ratio, 4.73; P = 0.0004) and TOP2A (hazard ratio, 3.06; P = 0.009) were independent predictors of relapse-free survival in multivariable analysis. These associations persisted when the analysis was further adjusted for demographic and histologic features of prognostic importance (RAD52 P = 0.01; TOP2A P = 0.02). Using principal component analysis, expression of DNA repair genes was summarized into one variable. Genes whose expression correlated with this variable were predominantly associated with the cell cycle and DNA repair. In 42 patients treated with chemotherapy, DNA repair gene expression was greater in tumors from patients who progressed on treatment. Further data supportive of a role for increased expression of DNA repair genes as predictive biomarkers are reported, which were generated using multiplex PCR. Conclusions: Overexpression of DNA repair genes (predominantly those involved in double-strand break repair) was associated with relapse. These data support the hypothesis that melanoma progression requires maintenance of genetic stability and give insight into mechanisms of melanoma drug resistance and potential therapies. Clin Cancer Res; 16(21); 5211–21. ©2010 AACR.

Melanoma sentinel node biopsy and prediction models for relapse and overall survival

Background:To optimise predictive models for sentinal node biopsy (SNB) positivity, relapse and survival, using clinico-pathological characteristics and osteopontin gene expression in primary melanomas.Methods:A comparison of the clinico-pathological characteristics of SNB positive and negative cases was carried out in 561 melanoma patients. In 199 patients, gene expression in formalin-fixed primary tumours was studied using Illuminas DASL assay. A cross validation approach was used to test prognostic predictive models and receiver operating characteristic curves were produced.Results:Independent predictors of SNB positivity were Breslow thickness, mitotic count and tumour site. Osteopontin expression best predicted SNB positivity (P=2.4 × 10−7), remaining significant in multivariable analysis. Osteopontin expression, combined with thickness, mitotic count and site, gave the best area under the curve (AUC) to predict SNB positivity (72.6%). Independent predictors of relapse-free survival were SNB status, thickness, site, ulceration and vessel invasion, whereas only SNB status and thickness predicted overall survival. Using clinico-pathological features (thickness, mitotic count, ulceration, vessel invasion, site, age and sex) gave a better AUC to predict relapse (71.0%) and survival (70.0%) than SNB status alone (57.0, 55.0%). In patients with gene expression data, the SNB status combined with the clinico-pathological features produced the best prediction of relapse (72.7%) and survival (69.0%), which was not increased further with osteopontin expression (72.7, 68.0%).Conclusion:Use of these models should be tested in other data sets in order to improve predictive and prognostic data for patients.

Atrophy of the intrinsic musculature of the hands associated with the use of botulinum toxin-A injections for hyperhidrosis: a case report and review of the literature.

Botulinum toxin type A (BTX-A) has been used therapeutically for the treatment of spastic disorders for many years. More recently, the therapeutic utility of BTX-A in the treatment of hyperhidrosis has been recognised. While studies have reported on the efficacy of BTX-A in managing hyperhidrosis, long term data are required in order for the treatment implications to be fully appreciated. We report on a case of severe atrophy of the intrinsic muscles of the hands in a patient treated with intra-palmar BTX-A (Dysport, Speywood, UK) injections for hyperhidrosis. To our knowledge this has not been described in the literature before.

Should Extraocular Sebaceous Carcinoma Be Investigated Using Sentinel Node Biospy

&NA; The authors have indicated no significant interest with commercial supporters.