| 2. |
- Harbst, Katja, et al.
(författare)
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Molecular profiling reveals low- and high-grade forms of primary melanoma.
- 2012
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 18:15, s. 4026-4036
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Tidskriftsartikel (refereegranskat)abstract
- For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome.We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data.Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets.We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease.
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| 3. |
- Tufvesson, Ellen, et al.
(författare)
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Levels of cysteinyl-leukotrienes in exhaled breath condensate are not due to saliva contamination
- 2010
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Ingår i: Clinical Respiratory Journal. - 1752-6981. ; 4:2, s. 83-88
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Saliva contamination has been suggested to be a major contributor to levels of cysteinyl leukotrienes in exhaled breath condensate (EBC). The aim of this study was to compare the levels of cysteinyl-leukotrienes (CysLT) and alpha-amylase activity in EBC to induced sputum and saliva collected from the same subjects (asthmatics and control). We thereby aimed to find out whether saliva contamination could be a plausible explanation to the levels found in EBC or not. Methods: EBC, saliva and induced sputum were collected from 11 asthmatic and 19 healthy adults. These samples were analyzed for CysLT concentration and alpha-amylase activity. Results: No significant correlation was found between CysLT concentration and alpha-amylase activity in EBC, saliva or sputum. In addition, we show that the saliva contamination (measured as alpha-amylase activity) was negligible, as the relative amount of saliva CysLT was only 0.6% of that found in EBC. The amount of CysLT correlated between all three compartments (EBC, saliva and sputum), but no similar correlation was seen for the alpha-amylase activity in EBC compared to saliva and sputum. The levels of CysLT were higher in asthmatic patients compared to healthy controls in EBC, saliva and sputum. Conclusion: We conclude that the amount of CysLT in EBC cannot be explained by saliva contamination. Please cite this paper as: Tufvesson E, van Weele LJ, Ekedahl H and Bjermer L. Levels of cysteinyl-leukotrienes in exhaled breath condensate are not due to saliva contamination. The Clinical Respiratory Journal 2010; 4: 83-88.
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