The objective of our study was to compare the five different scoring methods of tumor-infiltrating lymphocytes (TILs) assessment in a group of 213 cases of superficial spreading and nodular melanoma. The scoring methods include (a) Clark scoring; (b) Melanoma Institute Australia system; (c) scoring system used in the study of Saldanha et al.; (d) scoring system used in the TCGA study and modified by Park et al.; and (e) the system recently proposed by the "International Immuno-Oncology Biomarker Working Group" for TILs scoring in all solid tumors. Prediction of survival with three main outcomes-disease-specific-free survival, local recurrence-free survival, and distant metastasis-free survival-was evaluated. The prognostic value of TILs showed statistical significance in univariate analysis regarding all three of the outcomes only for three of the five evaluated methods; the Clark scoring, the Melanoma Institute Australia system, and the system proposed by the "International Immuno-Oncology Biomarker Working Group". However, in multivariate analysis with covariants including Breslow thickness, type of melanoma, location, sex, and age, we did not find TILs to be an independent prognostic factor.

• Klíčová slova
• nodular melanoma, prognosis, superficial spreading melanoma, tumor-infiltrating lymphocytes,
• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom klasifikace   imunologie   patologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory kůže imunologie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tumor infiltrující lymfocyty imunologie   MeSH
• výzkumný projekt MeSH
• zánět imunologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In certain primary and metastatic malignant melanomas diagnostic problems may arise due to their cytologic features and/or absence of synthesis of melanin. As the "classic" combination of S-100 protein and HMB-45 may occasionally fail to stain cells of malignant melanoma, we have tested a series of commercially accessible antibodies which were so far not compared by other authors in the three most frequent subtypes of this tumor. In surgical specimens from 104 cutaneous malignant melanomas (40 nodular melanomas, 46 superficially spreading malignant melanomas and 18 lentigo maligna melanomas) the staining intensity and the proportion of neoplastic cells stained with antibodies to S-100 protein, HMB-45, NKI/C3, NKI/beteb, MART 1 (Melan A), KBA 62 and Mitf was semiquantitatively analysed. The use of this group of antibodies against melanoma-associated antigens revealed it to be a favourable supplement for the bioptical or cytological diagnosis of malignant melanoma in case the traditional/conventional combination of S-100 protein and HMB-45 antibody fails. According to the authors' experience the antibody against KBA 62 has shown to be the most effective antibody followed by the antibodies against MART-1 (Melan A) and NKI/C3.

• MeSH
• antigeny nádorové analýza   MeSH
• diferenciační antigeny analýza   MeSH
• imunohistochemie MeSH
• lentigo maligna kůže imunologie   MeSH
• lidé MeSH
• melanom imunologie   patologie   MeSH
• monoklonální protilátky * MeSH
• nádorové biomarkery analýza   MeSH
• nádory kůže imunologie   patologie   MeSH
• specificita protilátek MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antigeny nádorové MeSH
• diferenciační antigeny MeSH
• monoklonální protilátky * MeSH
• nádorové biomarkery MeSH

Dermatological investigation offers a more precise clinical diagnosis of malignant melanoma in 20-30% of cases. It gives a correct visualization of melanocytic structures up to dermatoepidermal junction in ten fold magnification. A less distinct picture can be obtained from medium corial structures. Lentigo maligna melanoma and superficially spreading melanoma can be well distinguished from other pigmented lesions. Dermatoscopy offers an inspirative view between a clinical and microscopical picture plane.

• MeSH
• dermatoskopie * MeSH
• lentigo maligna kůže diagnóza   patologie   MeSH
• lidé MeSH
• melanom diagnóza   patologie   MeSH
• nádory kůže diagnóza   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

BACKGROUND: Cutaneous melanoma frequently develops on the lower limbs, but rarely on the feet, in people with light skin. By contrast, the feet are one of the most frequently affected sites in people with dark skin. This study assessed the prevalence and clinico-pathological findings of biopsy-proven skin melanomas that were diagnosed over 11 years. MATERIALS AND METHODS: The study group comprised 217 primary melanomas from 210 patients. RESULTS: Eight (3.7%) melanomas were located on the feet. These were all invasive and obtained from 8 patients (5 females and 3 males) aged 56-85 years (mean age 72 years). In general, the lesions were large (mean diameter 3.5cm) and had a high Breslow index (mean thickness 5.6mm). They were all ulcerated, and some invaded deep into the subcutaneous tissue. Histologic analyses demonstrated that three tumors exhibited features of acral lentiginous melanoma, two were nodular melanomas, and one was a superficial spreading melanoma. Two cases could not be histologically classified. CONCLUSION: Although skin melanomas arising on the feet are relatively rare in our ethnicity, they are usually bioptically diagnosed at an advanced stage. Such melanomas may initially imitate other pathologic entities. Therefore, this location should not be overlooked during the medical workup, and melanoma should be suspected when patients present with non-healing defects or local pigmented changes on the soles of the feet or toes. Key words: malignant melanoma - anatomic distribution - foot The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 9. 2. 2018 Accepted: 16. 5. 2018.

• Klíčová slova
• malignant melanoma - anatomic distribution - foot The authors declare they have no potential confl icts of interest concerning drugs, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 9. 2. 2018 Accepted: 16. 5. 2018, products,
• MeSH
• lidé středního věku MeSH
• lidé MeSH
• maligní melanom kůže MeSH
• melanom diagnóza   patologie   MeSH
• nádory kůže diagnóza   patologie   MeSH
• noha (od hlezna dolů) * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The incidence of malignant melanoma of the skin in the white population worldwide is rising and the mortality from this tumour is also rising. It is assumed that this trend will proceed also in coming years. While in 1970 in the Czech Republic 3.2 new cases of malignant melanoma per 100,000 population were reported, in 1990 the rate was already 8.1 and at present the number of notified cases is close to 10/100,000 population. An important risk factor for the development of malignant melanoma is solar radiation, in particular its UV component. Specially intermittent exposure of the skin to intense, even brief exposure to solar radiation with subsequent sunburn is very dangerous, in particular during childhood. People with type I and II skin are particularly threatened. The increased risk of development of malignant melanoma correlates also with the increased number of acquired melanocytic naevi. Investigation and evaluation of risk factor analyses facilitates screening of people at risk and their early treatment. In the clinical diagnosis four types of malignant melanoma of the skin are differentiated: lentigo maligna melanoma (LMM), superficially spreading melanoma (SSM), nodular melanoma (NM) and acrolentiginous melanoma (ALM). The author mentions the characteristics of different forms and signs which facilitate their early detection.

• MeSH
• lidé MeSH
• melanom * diagnóza   epidemiologie   etiologie   MeSH
• nádory kůže * diagnóza   epidemiologie   etiologie   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

UNLABELLED: Nestin is one of intermedial filaments exprimed in proliferating progenitor cells of the CNS and PNS (central and peripheral nervous system). Postnatal reexpression of the protein occures mainly in CNS tumors and correlates with a high grade of malignancy. The aim of our study is assessment of the nestin expression in benign and malignant skin melanocytic lesions with respect to presume a prognostic role of this protein. We examined 127 bioptic specimens, including 42 nodular melanomas (NM), 32 superficial spreading melanomas (SSM), 10 dysplastic nevi and 43 common intradermal or dermoepidermal nevi. We proved significant increase in nestin expression in melanoma groups, especially in nodular melanomas, where nestin was localized mainly in the peripheral, invasive areas of the tumor mass. CONCLUSION: Detection of nestin expression might be used as an additional melanocytic tumour marker.

• MeSH
• imunohistochemie MeSH
• lidé MeSH
• melanom chemie   patologie   MeSH
• nádory kůže chemie   patologie   MeSH
• nestin MeSH
• pigmentový névus chemie   patologie   MeSH
• progrese nemoci MeSH
• proteiny intermediálních filament analýza   MeSH
• proteiny nervové tkáně analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• NES protein, human MeSH Prohlížeč
• nestin MeSH
• proteiny intermediálních filament MeSH
• proteiny nervové tkáně MeSH

The most common histological subtypes of cutaneous melanoma include superficial spreading and nodular melanoma. However, the spectrum of somatic mutations developed in those lesions and all potential druggable targets have not yet been fully elucidated. We present the results of a sequence capture NGS analysis of 114 primary nodular and superficial spreading melanomas identifying driver mutations using biostatistical, immunohistochemical and/or functional approach. The spectrum and frequency of pathogenic or likely pathogenic variants were identified across 54 evaluated genes, including 59 novel mutations, and the newly identified TP53 loss-of-function mutations p.(L194P) and p.(R280K). Frequently mutated genes most commonly affected the MAPK pathway, followed by chromatin remodeling, and cell cycle regulation. Frequent aberrations were also detected in the genes coding for proteins involved in DNA repair and the regulation and modification of cellular tight junctions. Furthermore, relatively frequent mutations were described in KDR and MET, which represent potential clinically important targets. Those results suggest that with the development of new therapeutic possibilities, not only BRAF testing, but complex molecular testing of cutaneous melanoma may become an integral part of the decision process concerning the treatment of patients with melanoma.

• MeSH
• buněčný cyklus genetika   MeSH
• dospělí MeSH
• frekvence genu genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• maligní melanom kůže MeSH
• MAP kinasový signální systém genetika   MeSH
• melanom genetika   patologie   MeSH
• mladý dospělý MeSH
• mutace ztráty funkce genetika   MeSH
• nádorové biomarkery genetika   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory kůže genetika   patologie   MeSH
• oprava DNA genetika   MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• restrukturace chromatinu genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• těsný spoj genetika   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorové biomarkery MeSH
• nádorový supresorový protein p53 MeSH
• protoonkogenní proteiny B-Raf MeSH
• TP53 protein, human MeSH Prohlížeč

BACKGROUND: Nestin is one of the intermediate filaments that are expressed in proliferating neural progenitor cells during development of the central nervous system (CNS) and peripheral nervous system. Postnatal re-expression of the protein occurs mainly under pathological conditions, including injury and neoplasia. In this study, nestin expression was detected in both benign and malignant melanocytic skin lesions and its diagnostic relevance was then evaluated. METHODS: Altogether 139 bioptic tissue samples consisting of 42 nodular melanomas, 32 superficial spreading melanomas, 12 metastatic melanomas, 10 dysplastic nevi and 43 common melanocytic intradermal and dermoepidermal nevi were analysed using indirect immunohistochemical staining. RESULTS: We demonstrated that nestin immunostaining was significantly increased in melanomas where it correlated with more advanced stages of the disease. CONCLUSION: We conclude that expression of the intermediate filament protein nestin might be an indicator of tumor dedifferentiation and more aggressive behaviour. Furthermore, we suggest that nestin might be a relevant marker of tumorous and non-tumorous angiogenesis.

• MeSH
• imunohistochemie MeSH
• lidé MeSH
• melanom krevní zásobení   metabolismus   MeSH
• nádorové biomarkery analýza   MeSH
• nádory kůže krevní zásobení   metabolismus   MeSH
• nestin MeSH
• patologická angiogeneze metabolismus   MeSH
• pigmentový névus krevní zásobení   metabolismus   MeSH
• proteiny intermediálních filament biosyntéza   MeSH
• proteiny nervové tkáně biosyntéza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorové biomarkery MeSH
• NES protein, human MeSH Prohlížeč
• nestin MeSH
• proteiny intermediálních filament MeSH
• proteiny nervové tkáně MeSH

BACKGROUNDS: The principle behind the treatment of nephroblastoma has been similar for at least 4 decades, based on vincristine and dactinomycine, radiotherapy in selected stages. The last three decades have been characterised by the aim to reduce the intensity and length of treatment. DESIGN: To retrospectively compare survival rates and treatment success in a cohort of patients aged under 19 years, treated from 1980 to 2004 at a single centre by five consecutive treatment protocols. MATERIALS AND METHODS: The outcome was evaluated in patients treated consecutively by two protocols established at the centre before 1980 and modified in 1986, and from 1988 consecutively by three accepted protocols, SIOP9, SIOP93 and SIOP2001. RESULTS: Overall survival as well as event-free survival rates were evaluated by Kaplan-Meier functions in 315 patients (52.7% women). The average age at diagnosis was 3.9 +/- 2.9 years, median 3.3, range 0.01-17.2 years. Age over 12 years in 2.2% patients. The average follow-up time was 13.1 +/- 7.8, median 13.6, range 0.2-27.8 years. The original 104 weeks of protocol KDO86 treatment had a 10-year overall survival rate of 91.9 +/- 3.2%. Overall survival significantly fell with radiotherapy reduction in lower clinical stages and treatment diversification in protocols with substantial treatment length reduction. Overall survival returned to the original value of KDO86 only in 1994, when SIOP93 was accepted with a 10-year overall survival rate of 92.47 +/- 3.0% and event-free survival 85%, with similar trends in the latest protocol, SIOP2001. In the entire cohort two coincident malignancies (tumour duplicities) were found: one B-lymphoma, one neuroblastoma. A second malignancy occurred in one patient--superficial spreading melanoma. CONCLUSION: from the retrospective view the accepted SIOP9 protocol has a significantly worse outcome in both the overall survival and in event-free survival rate compared with the original therapy. Only the SIOP93 and SIOP2001 protocols accepted after 2003 have an acceptable 10-year overall survival rate (around 92%) as well as event-free survival (85%) with substantially reduced length and intensity of treatment, lowering the risk of late effects.

• MeSH
• dítě MeSH
• kojenec MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• míra přežití MeSH
• mladiství MeSH
• nádory ledvin mortalita   terapie   MeSH
• předškolní dítě MeSH
• přežití po terapii bez příznaků nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• Wilmsův nádor mortalita   terapie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH