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- Eriksson, Hanna, et al.
(författare)
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Interobserver Variability of Histopathological Prognostic Parameters in Cutaneous Malignant Melanoma : Impact on Patient Management
- 2013
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 93:4, s. 411-416
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Tidskriftsartikel (refereegranskat)abstract
- Clinical management of primary cutaneous melanomas is based on histopathological staging of the tumour. The aim of this study was to investigate, in a non-selected population in clinical practice, the agreement rate between general pathologists and pathologists experienced in melanoma in terms of the evaluation of histopathological prognostic parameters in cutaneous malignant melanomas, and to what extent the putative variability affected clinical management. A total of 234 cases of invasive cutaneous malignant melanoma were included in the study from the Stockholm-Gotland Healthcare Region in Sweden. Overall interobserver variability between a general pathologist and an expert review was 68.8-84.8%. Approximately 15.5% of melanomas <= 1 mm were re-classified either as melanoma in situ or melanomas >1 mm after review. In conclusion, review by a pathologist experienced in melanoma resulted in a change in recommendations about surgical excision margins and/or sentinel node biopsy in subgroups of Ti melanomas.
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| 2. |
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| 3. |
- Eriksson, Hanna, et al.
(författare)
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Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma : A nationwide population-based study in Sweden
- 2013
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Ingår i: European Journal of Cancer. - Oxford : Elsevier. - 0959-8049 .- 1879-0852. ; 49:12, s. 2705-2716
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden.METHODS:We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010.RESULTS:The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I=1.6; 95% confidence interval (CI)=1.5-1.7. OR stage III-IV versus I=2.3; 95% CI=1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high=2.02; 95% CI=1.80-2.26; p<0.0001) and intermediate (HR intermediate versus high=1.35; 95% CI=1.20-1.51; p<0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR=1.13; 95% CI=1.01-1.27; p=0.04) but not for intermediate versus high (HR=1.11; 95% CI=0.99-1.24; p=0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55years, patients with truncal tumours and during the first 5years after diagnosis.CONCLUSION:Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies.
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| 4. |
- Frohm Nilsson, Margareta
(författare)
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The human antimicrobial peptide hCAP18 in epithelial defense
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gene-encoded antimicrobial peptides serve a protective role in host defense. They are multifunctional effector molecules in innate immunity - the nonadaptive immune system -with the capacity to kill a broad spectrum of microorganisms. In contrast to adaptive immunity, which is highly specific, the innate immune system provides a rapid and nonspecific response, thereby contributing to the first line of defense. Cathelecidins constitute a family of antibacterial peptides. hCAP1 8, the precursor of the LL-37 antimicrobial peptide, is the only cathelecidin in humans while there are several in other species. We first analyzed fluid from wounds with different etiology for antibacterial and biochemical factors. We showed that wound fluid can be analyzed reproducibly and characterized biochemically. Separation and identification of such fluids yielded peptide components likely to reflect necrosis and to function as antibacterial and possible wound healing factors (Paper 1). We studied the role of hCAP1 8 in normal wound healing and in chronic non-healing ulcers. Using skin biopsies from healthy volunteers and from patients, we determined the level and expression pattern of hCAP1 8. Our results demonstrate the presence of hCAP1 8 in both types of wounds. Maximal levels of hCAP 18 were attained at 12h-2days post-wounding in surgical wounds. Total hCAP 18 protein levels in the chronic ulcers were below 20% of the maxima detected in the surgical wounds. Processed active LL-37 peptide was demonstrated in normal wound healing but was barely detectable in the chronic ulcers (Paper 2). In addition to providing a mechanical barrier between the body and the environment epithelia function as an immunological organ. Investigating the expression of hCAP 18 in inflammatory skin disorders we found up- regulation of the hCAP 18 gene in the keratinocytes of inflammatory dermatoses such as lesional psoriasis, nickel allergy and atopic dermatitis, but not in normal quiescent epidermis (Paper3). Further investigation of hCAP1 8 in squamous epithelia demonstrated that hCAP1 8 was constantly expressed at both RNA and protein levels in epithelia of tongue, esophagus, cervix and vagina. Expression of IL- 6 co-localized with hCAP 18 in these tissues. The hCAP 18 gene contains promotor elements that are potentially regulated by IL-6, and our findings suggest a potential local mechanism for the up-regulation of hCAP 18 on epithelial surfaces (Paper 4). To assess the potential role of hCAP 18 in tumor host defense, we investigated its expression in human breast cancer of varying types and malignancy. hCAP 18 was strongly up-regulated in the tumor cells compared to the low constitutive expression in normal benign mammary epithelia. Further, the highest levels of hCAP 18 protein were detected in the most malignant tumors, and immunoblotting revealed processed active LL-37 only in these tumors. Thus our results do not support a protective role for hCAP 18 in tumor host defense, but rather suggest that hCAP 18 may provide a survival advantage for the tumor (Paper 5). In summary our studies reveal a role for the innate immunity effector hCAP 18 in epithelial defense.
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| 6. |
- Mohr, Peter, et al.
(författare)
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Electrical impedance spectroscopy as a potential adjunct diagnostic tool for cutaneous melanoma
- 2013
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Ingår i: Skin research and technology. - : Wiley. - 0909-752X .- 1600-0846. ; 19:2, s. 75-83
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Tidskriftsartikel (refereegranskat)abstract
- Background Previous studies have shown statistically significant differences in electrical impedance between various cutaneous lesions. Electrical impedance spectroscopy (EIS) may therefore be able to aid clinicians in differentiating between benign and malignant skin lesions. Objectives The aim of the study was to develop a classification algorithm to distinguish between melanoma and benign lesions of the skin with a sensitivity of at least 98% and a specificity approximately 20 per cent higher than the diagnostic accuracy of dermatologists. Patients/Methods A total of 1300 lesions were collected in a multicentre, prospective, non-randomized clinical trial from 19 centres around Europe. All lesions were excised and subsequently evaluated independently by a panel of three expert dermatopathologists. From the data two classification algorithms were developed and verified. Results For the first classification algorithm, approximately 40% of the data were used for calibration and 60% for testing. The observed sensitivity for melanoma was 98.1% (101/103), non-melanoma skin cancer 100% (25/25) and dysplastic nevus with severe atypia 84.2% (32/38). The overall observed specificity was 23.6% (66/280). For the second classification algorithm, approximately 55% of the data were used for calibration. The observed sensitivity for melanoma was 99.4% (161/162), for non-melanoma skin cancer was 98.0% (49/50) and dysplastic nevus with severe atypia was 93.8% (60/64). The overall observed specificity was 24.5% (116/474). Conclusion EIS has the potential to be an adjunct diagnostic tool to help clinicians differentiate between benign and malignant (melanocytic and non-melanocytic) skin lesions. Further studies are needed to confirm the validity of the automatic assessment algorithm.
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| 7. |
- Simberg-Danell, Caroline, et al.
(författare)
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Prognostic factors and disease-specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden
- 2016
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Ingår i: International Journal of Cancer. - : WILEY-BLACKWELL. - 0020-7136 .- 1097-0215. ; 139:3, s. 543-553
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease-specific survival among first-and second-generation immigrants in Sweden. This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM, 1990-2007. Data were linked to nationwide, population-based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status, stage and CMM prognosis, respectively. After adjustments for confounders, first generation immigrants from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish-born patients [Stage II vs. I: Odds ratio (OR) = 2.37, 95% CI = 1.61-3.50. Stage III-IV vs I: OR=2.40, 95% CI = 1.08-5.37]. The ORs of stage II-IV versus stage I disease were increased among men (OR = 1.9; 95% CI = 1.1-3.3; p = 0.020), and women (OR = 4.8; 95% CI = 2.6-9.1; pamp;lt;0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-horn patients. The CMM-specific survival was significantly decreased among women from former Yugoslavia versus Swedish-born women [hazard ratio (HR)=2.2; 95 h CI = 1.1-4.2; p = 0.043]. After additional adjustments including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish-born patients were observed. In conclusion, a worse CMM-specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve the CMM prognosis.
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