A mini-symposium was held in Montreal, Canada, at the International Surgical Week for the Breast Surgical International in 2007 addressing the question whether breast cancer is the same disease in ...Asian and Western countries. Numerous investigators from Asian and Western countries presented the epidemiologic and clinical outcome data of women with breast cancer. Although there are significant similarities, the striking difference is that the peak age for breast cancer is between 40 and 50 years in the Asian countries, whereas the peak age in the Western countries is between 60 and 70 years. Also, the incidence of breast cancer in Asia is rising and is associated with increased mortality. In the West, although the incidence is increasing, the mortality rate is definitely decreasing. Future prospective data collection from Asian and Western countries may provide further interesting epidemiologic and outcome data regarding the outcome of women with breast cancer from Asian and Western countries.
Background
Whether breast cancer is the same disease in Asian and Western countries was the topic of a 2007 Breast Surgery International symposium at International Surgical Week.
Methods
Participating investigators from China, Taiwan, India, Japan, South Korea, Sweden, Canada, and the United States were asked beforehand to provide data on the epidemiology and treatment outcome of women in their countries.
Results
Comparisons of the epidemiologic and clinical outcome data of women with breast cancer showed significant similarities, but the striking difference is that the peak age is between 40 and 50 years in Asian countries, but is between 60 and 70 years in Western countries. The incidence of breast cancer in Asia is rising and is associated with increased mortality. In the West, although the incidence is also increasing, the mortality rate is definitely decreasing.
Discussion
Future prospective data collection from Asian and Western countries may provide further interesting epidemiologic and outcome data regarding the outcome of women with breast cancer from Asian and Western countries.
The Gene Expression Signatures of Melanoma Progression Haqq, Christopher; Nosrati, Mehdi; Sudilovsky, Daniel ...
Proceedings of the National Academy of Sciences - PNAS,
04/2005, Letnik:
102, Številka:
17
Journal Article
Recenzirano
Odprti dostop
Because of the paucity of available tissue, little information has previously been available regarding the gene expression profiles of primary melanomas. To understand the molecular basis of melanoma ...progression, we compared the gene expression profiles of a series of nevi, primary melanomas, and melanoma metastases. We found that metastatic melanomas exhibit two dichotomous patterns of gene expression, which unexpectedly reflect gene expression differences already apparent in comparing laser-capture microdissected radial and vertical phases of a large primary melanoma. Unsupervised hierarchical clustering accurately separated nevi and primary melanomas. Multiclass significance analysis of microarrays comparing normal skin, nevi, primary melanomas, and the two types of metastatic melanoma identified 2,602 transcripts that significantly correlated with sample class. These results suggest that melanoma pathogenesis can be understood as a series of distinct molecular events. The gene expression signatures identified here provide the basis for developing new diagnostics and targeting therapies for patients with malignant melanoma.
Background
99m
TcTilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared
99m
...Tctilmanocept to vital blue dye.
Methods
Patients received
99m
Tctilmanocept and blue dye. SLNs identified intraoperatively as radioactive and/or blue were excised and histologically examined. The primary end point, concordance, was the proportion of blue nodes detected by
99m
Tctilmanocept; 90 % concordance was the prespecified minimum concordance level. Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated. The prospective statistical plan combined the data from both trials.
Results
Fifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated. Intraoperatively, 232 of 235 blue nodes were detected by
99m
Tctilmanocept, for 98.7 % concordance (
p
< 0.001).
99m
TcTilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes).
99m
TcTilmanocept detected at least one node in more patients (
n
= 150) than blue dye (
n
= 138,
p
= 0.002). In 135 of 138 patients with at least one blue node, all blue nodes were radioactive. Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by
99m
Tctilmanocept, whereas blue dye detected only 36 (80 %) of 45 (
p
= 0.004). No positive SLNs were detected exclusively by blue dye. Four of 34 node-positive patients were identified only by
99m
Tctilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by
99m
Tctilmanocept. No serious adverse events were attributed to
99m
Tctilmanocept.
Conclusions
99m
TcTilmanocept met the prespecified concordance primary end point, identifying 98.7 % of blue nodes. It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye.
Bromodomain PHD finger transcription factor (BPTF) plays an important role in chromatin remodeling, but its functional role in tumor progression is incompletely understood. Here we explore the ...oncogenic effects of BPTF in melanoma.
The consequences of differential expression of BPTF were explored using shRNA-mediated knockdown in several melanoma cell lines. Immunoblotting was used to assess the expression of various proteins regulated by BPTF. The functional role of BPTF in melanoma progression was investigated using assays of colony formation, invasion, cell cycle, sensitivity to selective BRAF inhibitors, and in xenograft models of melanoma progression (n = 12 mice per group). The biomarker role of BPTF in melanoma progression was assessed using fluorescence in situ hybridization and immunohistochemical analyses. All statistical tests were two-sided.
shRNA-mediated BPTF silencing suppressed the proliferative capacity (by 65.5%) and metastatic potential (by 66.4%) of melanoma cells. Elevated BPTF copy number (mean ≥ 3) was observed in 28 of 77 (36.4%) melanomas. BPTF overexpression predicted poor survival in a cohort of 311 melanoma patients (distant metastasis-free survival P = .03, and disease-specific survival P = .008), and promoted resistance to BRAF inhibitors in melanoma cell lines. Metastatic melanoma tumors progressing on BRAF inhibitors contained low BPTF-expressing, apoptotic tumor cell subclones, indicating the continued presence of drug-responsive subclones within tumors demonstrating overall resistance to anti-BRAF agents.
These studies demonstrate multiple protumorigenic functions for BPTF and identify it as a novel target for anticancer therapy. They also suggest the combination of BPTF targeting with BRAF inhibitors as a novel therapeutic strategy for melanomas with mutant BRAF.
Guidelines for melanoma recommend sentinel lymph node biopsy (SLNB) in patients with melanomas ≥1 mm thickness. Recent single institution studies have found tumors <1.5 mm a low-risk group for ...positive SLNB.
A retrospective review of the Sentinel Lymph Node Working Group multicenter database identified patients with intermediate thickness melanoma (1.01–4.00 mm) who had SLNB, and assessed predictors for positive SLNB.
3460 patients were analyzed, 584 (17%) had a positive SLNB. Univariate factors associated with a positive SLNB included age <60 (p < .001), tumor on the trunk/lower extremity (p < .001), Breslow depth ≥2 mm (p < .001), ulceration (p < .001), mitotic rate ≥1/mm2 (p = .01), and microsatellitosis (p < .001). Multivariate analysis revealed age, location, and Breslow depth as significant predictors. Patients ≥75 with lesions 1.01–1.49 mm on the head/neck/upper extremity and 1.5–1.99 mm without high-risk features had <5% risk of SLN positivity.
Intermediate thickness melanoma has significant heterogeneity of SLNB positivity. Low-risk subgroups can be found among older patients in the absence of high-risk features.
•Intermediate thickness melanoma has heterogeneous risk for nodal metastases.•Groups that are low risk for nodal metastases may be spared a sentinel lymph node biopsy.•Elderly patients in particular may have low risk of nodal metastases.
Sentinel lymph nodes (SLNs), being the first nodes to receive lymph from a primary tumour and the preferential site of initial tumour metastases, are intensively exposed to the bioactive products of ...tumour cells and other associated cells. This makes them ideal for studies of the factors that determine selective tissue susceptibility to metastases. We postulate that tumour-induced immune modulation of SLNs facilitates lymph-node metastases by inhibiting the generation of tumour-specific cytotoxic T cells that are active against tumour cells of primary and metastatic melanomas. Immune modulation of the lymph nodes can be reversed by granulocyte/macrophage colony-stimulating factor (GM-CSF), a finding that has implications for the future therapy of lymph-node metastases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
Previous studies showed conflicting and inconsistent results regarding the effect of anatomic location of the melanoma on sentinel lymph node (SLN) positivity and/or survival. This study ...was conducted to evaluate and compare the effect of the anatomic locations of primary melanoma on long-term clinical outcomes.
Methods
All consecutive cutaneous melanoma patients (
n
= 2,079) who underwent selective SLN dissection (SLND) from 1993 to 2009 in a single academic tertiary-care medical center were included. SLN positive rate, disease-free survival (DFS), and overall survival (OS) were determined. Kaplan-Meier survival, univariate, and multivariate analyses were performed to determine predictive factors for SLN status, DFS, and OS.
Results
Head and neck melanoma (HNM) had the lowest SLN-positive rate at 10.8 % (16.8 % for extremity and 19.3 % for trunk;
P
= 0.002) but had the worst 5-year DFS (
P
< 0.0001) and 5-year OS (
P
< 0.0001) compared with other sites. Tumor thickness (
P
< 0.001), ulceration (
P
< 0.001), HNM location (
P
= 0.001), mitotic rate (
P
< 0.001), and decreasing age (
P
< 0.001) were independent predictive factors for SLN-positivity. HNM with T3 or T4 thickness had significantly lower SLN positive rate compared with other locations (
P
≤ 0.05). Also, on multivariate analysis, HNM location versus other anatomic sites was independently predictive of decreased DFS and OS (
P
< 0.001). By Kaplan-Meier analysis, HNM was associated significantly with the worst DFS and OS.
Conclusions
Primary melanoma anatomic location is an independent predictor of SLN status and survival. Although HNM has a decreased SLN-positivity rate, it shows a significantly increased risk of recurrence and death as compared with other sites.
To validate the prognostic impact of combined expression levels of three markers (SPP1, RGS1, and NCOA3) in melanoma specimens from patients enrolled in the E1690 clinical trial of high-dose or ...low-dose IFNα-2b versus observation.
Tissue was available from 248 patients. Marker expression was determined by digital imaging of immunohistochemically stained slides. The prognostic impact of each marker was first assessed by recording its expression value relative to the median. A multimarker index was then developed to combine marker expression levels by counting for each patient the number of markers with high expression. The impact of the multimarker index on relapse-free survival (RFS) and overall survival (OS) was assessed using Kaplan-Meier analysis, and both univariate and multivariate Cox regression analyses.
By Kaplan-Meier analysis, high multimarker expression scores were significantly predictive of RFS (
< 0.001) and OS (
< 0.001). Stepwise multivariate Cox regression analysis with backward elimination that included routine clinical and histologic prognostic factors revealed high multimarker expression scores and tumor thickness as the only factors significantly and independently predicting RFS and OS. Stepwise multivariate Cox regression analyses that also included treatment type and number of positive lymph nodes generated identical results for both RFS and OS. In the molecularly defined low-risk subgroup, patients treated with high-dose IFN had a significantly improved RFS compared with patients in the other two subgroups (
< 0.05).
These results validate the independent impact of combined expression levels of SPP1, RGS1, and NCOA3 on survival of melanoma in a prospectively collected cohort.
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