Preferentially expressed antigen of melanoma (PRAME) is a cancer/testis antigen selectively expressed in somatic tissues and various solid malignant tumors and is associated with poor prognostic outcome. Our research aimed to comprehensively compare its expression in a large cohort of tubo-ovarian epithelial tumors and examine its correlation with our clinico-pathologic data, as well as to assess its potential use in diagnostics and therapy.We examined 485 cases of epithelial tubo-ovarian tumors including 107 clear cell carcinomas (CCC), 52 endometroid carcinomas (EC), 103 high grade serous carcinomas (HGSC), 119 low grade serous carcinomas (LGSC)/micropapillary variant of serous borderline tumors (mSBT), and 104 cases of mucinous carcinomas (MC)/mucinous borderline tumors (MBT). The immunohistochemical analysis was performed using TMAs.The highest levels of expression were seen in EC (60%), HGSC (62%), and CCC (56%), while expression in LGSC/mSBT (4%) and MC/MBT (2%) was rare. The clinico-pathologic correlations and survival analysis showed no prognostic significance.The results of our study showed that PRAME is neither prognostic nor a suitable ancillary marker in the differential diagnosis of tubo-ovarian epithelial tumors. Nevertheless, knowledge about the PRAME expression may be important concerning its potential predictive significance, because targeting PRAME as a potential therapeutic option is currently under investigation.

• Klíčová slova
• Cancer, Immunohistochemistry, Ovarian tumors, PRAME,
• MeSH
• antigeny nádorové MeSH
• karcinom * patologie   MeSH
• lidé MeSH
• melanom * MeSH
• nádorové biomarkery analýza   MeSH
• nádory cystické, mucinózní a serózní * MeSH
• nádory vaječníků * MeSH
• serózní cystadenokarcinom * patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• Martius scarlet blue trichrome MeSH Prohlížeč
• nádorové biomarkery MeSH
• PRAME protein, human MeSH Prohlížeč

• Klíčová slova
• Adaptive immunity, Immunoglobulins, Immunology,
• MeSH
• antigeny nádorové * genetika   MeSH
• B-buněčný lymfom * genetika   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• Názvy látek
• antigeny nádorové * MeSH
• PRAME protein, human MeSH Prohlížeč

Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used in pathology for the assessment of melanocytic neoplasms; however, knowledge of its expression patterns in soft tissue tumors is limited. PRAME immunohistochemistry (clone QR005) was assessed on whole tissue sections of 350 soft-tissue tumors and mimics (> 50 histotypes). PRAME immunoreactivity was evaluated as follows: 0 "negative" (0% positive cells); 1+ (1-25% positive cells); 2+ (26-50% positive cells); 3+ (51-75% positive cells), and 4+ "diffuse" (> 75% positive cells). PRAME was expressed in 111 lesions (0 benign, 6 intermediate malignancy, and 105 malignant), including fibrosarcomatous dermatofibrosarcoma protuberans (2/4, 0 diffuse), NTRK-rearranged spindle cell neoplasm (2/4, 0 diffuse), atypical fibroxanthoma (1/7, 0 diffuse), Kaposi sarcoma (1/5, 0 diffuse), myxoid liposarcoma (11/11, 9 diffuse), synovial sarcoma (11/11, 6 diffuse), intimal sarcoma (7/7, 5 diffuse), biphenotypic sinonasal sarcoma (3/3, 1 diffuse), angiosarcoma (10/15, 6 diffuse), malignant peripheral nerve sheath tumor (9/12, 4 diffuse), pleomorphic rhabdomyosarcoma (2/3, 2 diffuse), alveolar rhabdomyosarcoma (2/6, 0 diffuse), embryonal rhabdomyosarcoma (7/7, 4 diffuse), undifferentiated pleomorphic sarcoma (2/12, 1 diffuse), leiomyosarcoma (2/15, 1 diffuse), clear cell sarcoma of soft tissue (1/10, 0 diffuse), low-grade fibromyxoid sarcoma (1/5, 0 diffuse), Ewing sarcoma (2/10, 1 diffuse), CIC-rearranged sarcoma (8/8, 4 diffuse), BCOR-sarcoma (2/5, 1 diffuse), melanoma (20/20, 14 diffuse), and thoracic SMARCA4-deficient undifferentiated tumor (5/5, all diffuse). All tested cases of spindle cell lipoma, dedifferentiated/pleomorphic liposarcoma, dermatofibrosarcoma protuberans, solitary fibrous tumor, inflammatory myofibroblastic tumor, myxoinflammatory fibroblastic sarcoma, nodular fasciitis, myxofibrosarcoma, epithelioid hemangioendothelioma, atypical vascular lesion, hemangioma, lymphangioma, vascular malformation, papillary endothelial hyperplasia, GIST, gastrointestinal clear-cell sarcoma, malignant melanotic nerve sheath tumor, neurofibroma, schwannoma, granular cell tumor, alveolar soft part sarcoma, epithelioid sarcoma, extraskeletal myxoid chondrosarcoma, myoepithelioma, ossifying fibromyxoid tumor, angiomatoid fibrous histiocytoma, PEComa, dermatofibroma, pleomorphic dermal sarcoma, and chordoma were negative. PRAME shows imperfect specificity in soft-tissue pathology but may serve as a diagnostic adjunct in selected differential diagnoses that show contrasting expression patterns.

• Klíčová slova
• Differential diagnosis, Immunohistochemistry, Immunotherapy, Melanoma, PRAME, Sarcoma, Soft tissue,
• MeSH
• antigeny nádorové MeSH
• diferenciální diagnóza MeSH
• DNA-helikasy MeSH
• dospělí MeSH
• Ewingův sarkom * diagnóza   MeSH
• fibrosarkom * diagnóza   MeSH
• imunohistochemie MeSH
• jaderné proteiny MeSH
• lidé MeSH
• melanom * patologie   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory kůže * patologie   MeSH
• nádory měkkých tkání * diagnóza   patologie   MeSH
• sarkom * diagnóza   patologie   MeSH
• transkripční faktory MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• DNA-helikasy MeSH
• jaderné proteiny MeSH
• nádorové biomarkery MeSH
• PRAME protein, human MeSH Prohlížeč
• SMARCA4 protein, human MeSH Prohlížeč
• transkripční faktory MeSH

• Klíčová slova
• array CGH, chronic lymphocytic leukaemia, deletion, lambda light chain, loss of 22q11,
• MeSH
• antigeny nádorové genetika   MeSH
• chromozomální delece * MeSH
• chronická lymfatická leukemie diagnóza   genetika   MeSH
• genetické lokusy * MeSH
• imunoglobuliny - lambda-řetězce genetika   MeSH
• lehké řetězce imunoglobulinů genetika   MeSH
• lidé MeSH
• lidské chromozomy, pár 22 * MeSH
• nádorové biomarkery MeSH
• represorové proteiny genetika   MeSH
• srovnávací genomová hybridizace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny nádorové MeSH
• imunoglobuliny - lambda-řetězce MeSH
• lehké řetězce imunoglobulinů MeSH
• nádorové biomarkery MeSH
• PRAME protein, human MeSH Prohlížeč
• represorové proteiny MeSH
• ZNF280B protein, human MeSH Prohlížeč

We report a very unusual case of melanocytic neoplasm appearing clinically as a 0.5-cm dome-shaped pigmented papule on the chest of a 63-year-old man. Microscopically, it was an asymmetric, entirely dermally based neoplasm characterized by a multinodular, vaguely plexiform architecture composed of moderately pleomorphic spindled melanocytes with ample, dusty pigmented cytoplasm and scattered multinucleated cells. The tumor cells were strongly positive for Melan-A, HMB45, S100, and PRAME, whereas p16 showed diffuse nuclear loss. β-catenin presented a strong and diffuse cytoplasmic staining, while nuclei were negative. Despite an increased cellularity, mitotic count was low (1/mm 2 ). Fluorescence in situ hybridization revealed no copy number alteration in melanoma-related genes ( CDKN2A, MYB, MYC, CCND1 and RREB1 ). DNA and RNA sequencing identified KIT c.2458G>T and APC c.6709C>T mutations. No further genetic alteration was detected including TERT-promoter (TERT-p ) hot-spot mutation. A re-excision was performed. A sentinel lymph node biopsy was negative. Clinical investigations revealed no extracutaneous involvement. The patient is disease-free after a follow-up period of 8 months. Given the peculiar morphologic and molecular findings, we hypothesize the lesion may represent a novel subtype of an intermediate grade melanocytic tumor (melanocytoma).

• MeSH
• antigeny nádorové MeSH
• biopsie sentinelové lymfatické uzliny MeSH
• hybridizace in situ fluorescenční MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanocyty patologie   MeSH
• melanom * patologie   MeSH
• mutace MeSH
• nádory kůže * patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antigeny nádorové MeSH
• PRAME protein, human MeSH Prohlížeč

Allogeneic cancer cell lines serve as universal source of tumor-associated antigens in cancer vaccines. Immunogenic high hydrostatic pressure-killed cancer cells derived from cell lines can be used for the generation of dendritic cell (DC)-based active cellular immunotherapy of non-small cell lung cancer (NSCLC). We investigated the expression of 12 known NSCLC tumor-associated antigens (TAA) (CEA, MAGE-A1, MAGE-A3, MAGE-A4, PRAME, hTERT, HER2, MUC1, Survivin, STEAP1, SOX2 and NY-ESO-1) in 6 NSCLC cell lines as candidates for the generation of DC-based lung cancer vaccine. We showed that the selected antigenic profile of these cell lines overlaps to various degrees with that of primary NSCLC tumors (n = 52), indicating that 4 out of 6 NSCLC cell lines would be suitable for DC-based vaccine generation. We further investigated the presence of TAA-specific T cells in blood of NSCLC patients (n = 32) using commercially available peptide mixes in an in vitro stimulation assay. IFN-γ+CD8+ and IFN-γ+CD4+ T cell responses to all antigens were detected in NSCLC patients. Interestingly, despite higher TAA expression in squamous cell carcinoma (SCC) the responsiveness of patients' T cells to stimulation was significantly lower in SCC patients than in adenocarcinoma (AC) patients. This suggests qualitative differences in T cell functionality between NSCLC subtypes. Based on this study, and in order to maximize the amount of treatable patients, we selected a mix of H520 and H522 NSCLC cell lines for DC-based vaccine preparation. We also established a minimal panel of antigenic peptide mixes (CEA, hTERT, PRAME, HER2) for immunomonitoring of T cell responses during the DC-based lung cancer immunotherapy in Phase I lung cancer clinical trial (NCT02470468).

• Klíčová slova
• Cancer cell lines, Dendritic cell-based immunotherapy, Immunomonitoring, Non-small cell lung cancer, T cells, Tumor antigens,
• MeSH
• antigenní specifita receptorů T-buněk * MeSH
• antigeny nádorové imunologie   MeSH
• cytotoxické T-lymfocyty imunologie   metabolismus   MeSH
• dendritické buňky imunologie   metabolismus   MeSH
• imunoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory plic imunologie   metabolismus   patologie   terapie   MeSH
• nemalobuněčný karcinom plic imunologie   metabolismus   patologie   terapie   MeSH
• protinádorové vakcíny MeSH
• senioři MeSH
• staging nádorů MeSH
• T-lymfocyty imunologie   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny nádorové MeSH
• protinádorové vakcíny MeSH

In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelial ovarian cancer tissue. More than 90% of tumor samples expressed very high levels of CA125, FOLR1, EPCAM and MUC-1 and elevated levels of Her-2/neu, similarly to OVCAR-3 cell line. The combination of OV-90 and OVCAR-3 cell lines showed the highest overlap with patients' samples in the TAA expression profile.

• Klíčová slova
• cancer cell lines, high-grade serous epithelial ovarian cancer, immunotherapy, tumor-associated antigens,
• MeSH
• antigeny nádorové analýza   MeSH
• dospělí MeSH
• epiteliální ovariální karcinom MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádorové buněčné linie MeSH
• nádorové buňky kultivované MeSH
• nádory glandulární a epitelové imunologie   MeSH
• nádory vaječníků imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• transkriptom * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• nádorové biomarkery MeSH

The technology of array comparative genomic hybridization (array-CGH/aCGH) enabled the identification of novel genomic aberrations in chronic lymphocytic leukemia (CLL) including the monoallelic and biallelic deletions affecting 22q11 locus. In contrast to previous publications, we hypothesized that the described 22q11 deletions are a consequence of the rearrangement of immunoglobulin lambda light chain locus (IGL) segments surrounding several protein-coding genes located in this region. Indeed, using array-CGH and PCR analysis we show that all deletions (n=7) affecting the 22q11 locus in our cohort (n=40) are based on the physiological mechanism of IGL rearrangement. This demonstrates that this loss of genetic material is likely not pathogenic and in fact is merely a marker of IGL rearrangement.

• MeSH
• antigeny nádorové genetika   MeSH
• chromozomální delece * MeSH
• chronická lymfatická leukemie genetika   MeSH
• dospělí MeSH
• genová přestavba * MeSH
• hybridizace in situ fluorescenční MeSH
• imunoglobuliny - lambda-řetězce genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 22 genetika   MeSH
• následné studie MeSH
• polymerázová řetězová reakce MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srovnávací genomová hybridizace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé 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
• antigeny nádorové MeSH
• imunoglobuliny - lambda-řetězce MeSH
• PRAME protein, human MeSH Prohlížeč

AIMS: This study aimed to examine changes in the repertoire of functional T-cells specific for six leukemia-associated antigens (LAA), including WT1, PRAME, MUC1, CCNA1, NPM1, and NPM1c, during immune reconstitution following allogeneic transplantation of hematopoietic stem cells (HSCT) in patients with acute myeloid leukemia. PATIENTS & METHODS: LAA-specific T cell response was measured by ELISPOT- IFNγ and intracellular cytokine staining in 47 patients before starting conditioning therapy (baseline) and 7 months after HSCT. RESULTS: The positive cumulative LAA-specific T cell response before HSCT was associated with a decreased risk of relapse after HSCT. The prevalent genetic aberration - an internal tandem duplication of Fms 3 - related receptor tyrosine kinase, which has been previously implicated in immune escape mechanisms, is presented here for the first time as a factor associated with the absence of an adaptive T cell response against multiple LAAs. T-cell specific responses against wild-type and mutated NPM1 antigens were less frequent in the study cohort and did not correlate with mutations in the NPM1 gene. CONCLUSIONS: Our results showed that the T-cell response to LAA can be reconstituted after HSCT. Measurement of functional pre-transplant T-cell responses against multiple LAAs could help to find patients with an increased risk of relapse.

• Klíčová slova
• ELISPOT-interferon gamma, Flt3-ITD, Leukemia associated antigen, T cell response, acute myeloid leukemia, hematopoietic stem cell transplantation, relapse,
• MeSH
• akutní myeloidní leukemie * terapie   imunologie   genetika   MeSH
• antigeny nádorové imunologie   MeSH
• dospělí MeSH
• homologní transplantace MeSH
• jaderné proteiny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mucin 1 genetika   imunologie   MeSH
• mutace * MeSH
• nukleofosmin * MeSH
• proteiny WT1 imunologie   genetika   MeSH
• recidiva MeSH
• senioři MeSH
• T-lymfocyty * imunologie   MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• tyrosinkinasa 3 podobná fms * genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• FLT3 protein, human MeSH Prohlížeč
• jaderné proteiny MeSH
• MUC1 protein, human MeSH Prohlížeč
• mucin 1 MeSH
• NPM1 protein, human MeSH Prohlížeč
• nukleofosmin * MeSH
• proteiny WT1 MeSH
• tyrosinkinasa 3 podobná fms * MeSH
• WT1 protein, human MeSH Prohlížeč