Salivary duct carcinoma Dotaz Zobrazit nápovědu
Salivary duct carcinoma (SDC) is one of the most aggressive salivary gland tumors, and prognosis remains poor for most patients. The aim of this study was to investigate the prognostic implications of biomarker immunoprofile in a cohort of SDC and to identify molecular characteristics through next-generation sequencing (NGS) in a subset of cases. Clinicopathological and follow-up information of 25 cases diagnosed as SDC was collected. Immunoexpression of AR, HER-2/neu, GATA3, CK5/6, and MIB1 was analyzed, and ERBB2 (HER-2/Neu) gene amplification was investigated by fluorescence in situ hybridization. Cases were classified under the "SDC revised classification system." Eight SDC cases were analyzed by targeted NGS for detection of gene fusions and variants. Overall survival and disease-free survival were analyzed with Kaplan-Meier curves and Cox regression. Most cases expressed AR (100%), GATA3 (73%), and CK5/6 (76.5%), and 42% expressed HER-2/neu. ERBB2 gene amplification was proven by fluorescence in situ hybridization in 7 of 15 (46%) cases. Apocrine HER2 (AR+/HER2+) subtype was significantly associated with lower overall survival (P = .05). NGS analysis revealed 9 pathogenic mutations in 7 SDC cases, and the most frequently mutated gene was HRAS (4/9) followed by PIK3CA (2/9) and TP53 (2/9). One case (1/9) presented homozygous deletion of locus 9p21 (CDKN2A), and another case (1/9) showed MDM2 amplification. In conclusion, we demonstrated that Apocrine HER2 (AR+/HER2+) is a potential biomarker of poor outcome in SDC. Furthermore, NGS analysis revealed recurrent mutations in SDC.
- Klíčová slova
- Immunoprofile, NGS, Prognosis, Salivary duct carcinoma, Salivary gland neoplasm,
- MeSH
- dospělí MeSH
- duktální karcinom diagnóza patologie MeSH
- homozygot MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace genetika MeSH
- nádorové biomarkery analýza MeSH
- nádory slinných žláz diagnóza genetika patologie MeSH
- sekvenční delece genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- vývody slinných žláz patologie 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
- nádorové biomarkery MeSH
AIMS: The aim of this study was to devise a molecular classification for salivary duct carcinomas (SDCs) based on the similarities between SDCs and breast carcinomas and on characteristics of the microarray-based gene expression profiling-defined molecular subtypes of breast cancer. METHODS AND RESULTS: Forty-two pure salivary duct carcinomas, 35 of which contained an in-situ component as defined by histological review and/or immunohistochemical analysis, were stained with antibodies for oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6. Based on these markers, tumours were classified into HER2, luminal androgen receptor-positive, basal-like, luminal and indeterminate phenotype. Analysis revealed that 16.7%, 69%, 4.8%, 9.5% and 0% were of HER2, luminal androgen receptor-positive, basal-like, indeterminate and luminal phenotype, respectively. The in-situ and invasive components displayed the same molecular subtype in all but one case. CONCLUSION: Salivary duct carcinomas can be classified into molecular subgroups approximately equivalent to those in the breast. We also report on the existence of a subgroup of bona fide pure salivary duct carcinomas that have a 'basal-like' phenotype. Understanding the phenotypic complexity of SDCs may help to expedite the identification of novel therapeutic targets for these aggressive tumours.
- Klíčová slova
- HER2, androgen receptor, basal cytokeratins, basal-like phenotype, molecular subtypes, salivary duct carcinoma,
- MeSH
- androgenní receptory analýza biosyntéza genetika MeSH
- čipová analýza tkání MeSH
- dospělí MeSH
- duktální karcinom klasifikace genetika patologie MeSH
- fenotyp MeSH
- hybridizace in situ MeSH
- imunohistochemie MeSH
- karcinom in situ klasifikace genetika patologie MeSH
- karcinom klasifikace genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory slinných žláz klasifikace genetika patologie MeSH
- receptor erbB-2 analýza biosyntéza genetika MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transkriptom MeSH
- vývody slinných žláz patologie 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
- androgenní receptory MeSH
- AR protein, human MeSH Prohlížeč
- ERBB2 protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
- receptor erbB-2 MeSH
Salivary duct carcinoma (SDC) is a highly malignant salivary gland tumor with aggressive clinical behavior, and is characterized by its histological resemblance to invasive ductal carcinoma of the breast. Overexpression and/or amplification of proto-oncogene Her2/neu has been shown to influence both prognosis and treatment of breast cancer. Since salivary duct carcinoma and ductal breast carcinoma share many common characteristics, HER2/neu overexpression might also be important in SDC. However, data on the expression of c-erbB2/HER2/neu in salivary gland tumors are still scarce. Therefore, we have evaluated 15 cases of salivary duct carcinomas (SDC) for HER2/neu overexpression using immunohistochemistry with the HercepTest. Overexpression, identified as strong or moderate membrane immunostaining, was observed in all but one case of SDC in most neoplastic cells. Thus, our study suggests that anti-HER2/neu therapy with Herceptin is beneficial for patients with aggressive salivary duct carcinoma.
- MeSH
- antigeny jaderné MeSH
- antitumorózní látky terapeutické užití MeSH
- dospělí MeSH
- humanizované monoklonální protilátky MeSH
- imunoenzymatické techniky MeSH
- jaderné proteiny analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- lymfatické uzliny patologie MeSH
- monoklonální protilátky terapeutické užití MeSH
- nádorové biomarkery analýza MeSH
- nádory slinných žláz metabolismus patologie terapie MeSH
- počet buněk MeSH
- protoonkogen Mas MeSH
- reagenční diagnostické soupravy MeSH
- receptor erbB-2 analýza biosyntéza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- trastuzumab 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
- Názvy látek
- antigeny jaderné MeSH
- antitumorózní látky MeSH
- humanizované monoklonální protilátky MeSH
- jaderné proteiny MeSH
- MAS1 protein, human MeSH Prohlížeč
- monoklonální protilátky MeSH
- nádorové biomarkery MeSH
- protoonkogen Mas MeSH
- reagenční diagnostické soupravy MeSH
- receptor erbB-2 MeSH
- trastuzumab MeSH
Low-grade cribriform cystadenocarcinoma of salivary glands is a recently described rare tumor with favorable prognosis. This study reports the case of 50-year-old woman with swelling lasting for 9 months in the right parotideomasseteric area. Grossly, the tumor was well circumscribed and dominated by cystic space. Microscopically, the neoplasm consisted of well-demarcated islets, some of them cystically dilated. The architecture of islets varied from solid to cribriform and micropapillary without comedo-type necroses. The tumor cells featured no significant cytologic atypia. Immunohistochemically, luminal cells showed expression of cytokeratins (CK), CK7, CK18, and S100 protein. In addition, immunostains for CK5/6, CK14, p63 protein, and smooth muscle actin displayed a continuous rim of myoepithelial cells around all tumor nests. In contrast, detection of CK20, hormonal receptors (androgen, estrogen, and progesterone), epidermal growth factor receptor and Her-2/neu oncoprotein was negative. The patient is free of disease for 2 years. The relationship between low-grade cribriform cystadenocarcinoma and salivary duct carcinoma is discussed.
- MeSH
- cystadenokarcinom metabolismus patologie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádory příušní žlázy metabolismus patologie chirurgie MeSH
- nádory slinných žláz patologie MeSH
- přežití po terapii bez příznaků nemoci MeSH
- prognóza MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- nádorové biomarkery MeSH
AIMS: Secretory carcinoma (SC) (synonym: mammary analogue secretory carcinoma) is a low-grade salivary gland tumour that occurs in both major and minor salivary glands. SC is known for its wide morphological, architectural and immunohistochemical spectrum, which overlaps with those of several salivary gland neoplasms, including acinic cell carcinoma (AciCC) and intercalated duct-type intraductal carcinoma (IDC) in major salivary glands, and polymorphous adenocarcinoma (PAC) in minor salivary glands. These tumours share with SC some morphological features and SOX10 immunoreactivity; also, with the exception of AciCC, they all coexpress S100 and mammaglobin. METHODS AND RESULTS: We compared MUC4 and mammaglobin expression in 125 salivary gland carcinomas (54 genetically confirmed SCs, 20 AciCCs, 21 PACs, and 30 IDCs) to evaluate the potential of these two markers to differentiate these entities. Moderate to strong diffuse MUC4 positivity was detected in 49 SCs (90.7%), as compared with none of the IDCs and PACs. In contrast, mammaglobin was frequently expressed in SCs (30 of 36 cases; 83.3%), IDCs (24/28; 85.7%), and PACs (7/19; 36.8%). Two of three high-grade SCs lost MUC4 expression in the high-grade tumour component. No significant correlation was found between MUC4 expression and the fusion variant in SC (ETV6-NTRK versus non-ETV6-NTRK). CONCLUSION: The results of our study identify MUC4 as a sensitive (90.7%) and specific (100%) marker for SC, with high positive (100%) and negative (93.4%) predictive values. Thus, MUC4 may be used as a surrogate for SC in limited biopsy material and in cases with equivocal morphology.
- Klíčová slova
- MUC4, acinic cell carcinoma, immunohistochemistry, intraductal carcinoma, mammaglobin, polymorphous adenocarcinoma, secretory carcinoma,
- MeSH
- acinární karcinom diagnóza patologie MeSH
- diferenciální diagnóza * MeSH
- karcinom diagnóza patologie MeSH
- lidé MeSH
- mammaglobin A metabolismus MeSH
- mucin 4 analýza MeSH
- nádorové biomarkery analýza MeSH
- nádory slinných žláz * diagnóza metabolismus patologie MeSH
- sekreční karcinom mamárního typu diagnóza metabolismus patologie MeSH
- slinné žlázy patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mammaglobin A MeSH
- MUC4 protein, human MeSH Prohlížeč
- mucin 4 MeSH
- nádorové biomarkery MeSH
AIMS: Salivary duct carcinoma is a highly malignant salivary gland tumour with aggressive clinical behaviour, characterized by histological resemblance to invasive ductal carcinoma of the breast. Amplification of HER-2/neu oncogene and over-expression of its gene product have both prognostic and therapeutic implications in breast cancer. Recent report on salivary duct carcinomas for HER-2/neu using immunohistochemistry (IHC) has shown over-expression in most cases. However, correlation between IHC and molecular genetic analysis of HER-2/neu in salivary duct carcinoma has not yet been performed. METHODS AND RESULTS: We have now evaluated 11 cases of salivary duct carcinomas for HER-2/neu status using IHC and fluorescent in-situ hybridization (FISH). To our knowledge, this is the first molecular genetic analysis of HER-2/neu in salivary duct carcinoma. CONCLUSIONS: In immunohistochemistry, over-expression of HER-2/neu protein was identified as distinct membrane staining in most carcinoma cells in all our salivary duct carcinoma cases, while only four cases revealed an amplification of HER-2/neu gene by means of FISH analysis. Both amplified and non-amplified salivary duct carcinomas with strong immunohistochemical staining for HER-2/neu protein were associated with poor clinical outcome for the patients. Apparently, HER-2/neu protein over-expression could also be controlled by mechanisms other than gene amplification. In the group of salivary gland tumours other than salivary duct carcinoma, strong over-expression was detected only in three cases of carcinoma ex pleomorphic adenoma. Thus, over-expression of HER-2/neu protein is also a useful marker of malignant transformation in pleomorphic adenomas.
- MeSH
- amplifikace genu MeSH
- dospělí MeSH
- exprese genu genetika MeSH
- geny erbB-2 * MeSH
- hybridizace in situ fluorescenční MeSH
- imunoenzymatické techniky MeSH
- karcinom genetika metabolismus sekundární MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory příušní žlázy genetika metabolismus patologie MeSH
- receptor erbB-2 * genetika metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vývody slinných žláz * patologie 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
- Názvy látek
- receptor erbB-2 * MeSH
The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours features a description and inclusion of several new entities, including sclerosing polycystic adenoma, keratocystoma, intercalated duct adenoma, and striated duct adenoma among the benign neoplasms; and microsecretory adenocarcinoma and sclerosing microcystic adenocarcinoma as the new malignant entities. The new entry also includes mucinous adenocarcinoma subdivided into papillary, colloid, signet ring, and mixed subtypes with recurrent AKT1 E17K mutations across patterns suggesting that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that may be related to salivary intraductal papillary mucinous neoplasm (IPMN). Importantly, the number of entities in the salivary chapter has been reduced by omitting tumors or lesions if they do not occur exclusively or predominantly in salivary glands, including hemangioma, lipoma, nodular fasciitis and hematolymphoid tumors. They are now discussed in detail elsewhere in the book. Cribriform adenocarcinoma of salivary gland origin (CASG) now represents a distinctive subtype of polymorphous adenocarcinoma (PAC). PAC is defined as a clinically, histologically and molecularly heterogeneous disease group. Whether CASG is a different diagnostic category or a variant of PAC is still controversial. Poorly differentiated carcinomas and oncocytic carcinomas are discussed in the category "Salivary carcinoma not otherwise specified (NOS) and emerging entities". New defining genomic alterations have been characterized in many salivary gland tumors. In particular, they include gene fusions, which have shown to be tightly tumor-type specific, and thus valuable for use in diagnostically challenging cases. The recurrent molecular alterations were included in the definition of mucoepidermoid carcinoma, adenoid cystic carcinoma, secretory carcinoma, polymorphous adenocarcinoma, hyalinizing clear cell carcinoma, mucinous adenocarcinoma, and microsecretory adenocarcinoma.
- Klíčová slova
- Classification, Gene fusion, Neoplasm, Salivary gland, WHO, World Health Organization,
- MeSH
- adenokarcinom * patologie MeSH
- adenom * genetika patologie MeSH
- lidé MeSH
- mucinózní adenokarcinom * MeSH
- nádorové biomarkery genetika MeSH
- nádory slinných žláz * genetika patologie MeSH
- slinné žlázy patologie MeSH
- Světová zdravotnická organizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery MeSH
Salivary duct carcinoma (SDC) is highly malignant salivary gland tumour with aggressive clinical behaviour, characterised by its histological resemblance to invasive ductal carcinoma of the breast. Amplification of gene HER-2/neu and overexpression of its gene product have been shown to have both prognostic and treatment implications in breast cancer. The reports concerning the expression of c-erbB2/HER-2/neu in salivary gland tumours are few and controversial. Thus, eleven cases of SDC were evaluated for HER-2/neu status using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). To the best of our knowledge, this is the first molecular genetic analysis of SDCs using FISH. HER-2/neu overexpression, identified as strong membrane staining, was observed in all but one case of SDC in majority of neoplastic cells while only four tumours, of nine cases analysed, revealed HER-2/neu gene amplification by means of FISH analysis. SDCs were associated with poor clinical outcome, 6 patients (55%) died of disseminated carcinoma within 4 to 44 months after therapy. There was no difference in outcome of patients with IHC positive-nonamplified and IHC positive-amplified tumours.
- MeSH
- amplifikace genu * MeSH
- dospělí MeSH
- geny erbB-2 genetika MeSH
- hybridizace in situ fluorescenční MeSH
- imunohistochemie MeSH
- karcinom chemie genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory příušní žlázy chemie genetika MeSH
- receptor erbB-2 analýza MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vývody slinných žláz * 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
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- receptor erbB-2 MeSH
Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.
- MeSH
- biopsie MeSH
- diagnostické techniky molekulární * MeSH
- diferenciální diagnóza MeSH
- fenotyp MeSH
- fúze genů MeSH
- genetická predispozice k nemoci MeSH
- karcinom genetika patologie terapie MeSH
- lidé MeSH
- mutace MeSH
- nádorové biomarkery genetika MeSH
- nádory slinných žláz genetika patologie terapie MeSH
- prediktivní hodnota testů MeSH
- stupeň nádoru MeSH
- translokace genetická MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- nádorové biomarkery MeSH
Intraductal carcinoma (IC) is the new WHO designation for tumors previously encompassed by "low-grade cribriform cystadenocarcinoma" and "low-grade salivary duct carcinoma." The relationship of IC to salivary duct carcinoma (SDC) is controversial, even though they are considered to be distinct entities. IC is a rare low-grade malignant salivary gland neoplasm with histopathological features reminiscent of atypical ductal hyperplasia or ductal carcinoma in situ of the breast, showing diffuse S100 protein and mammaglobin positivity, while it is partially defined genetically. Recently, RET rearrangements including NCOA4-RET and TRIM27-RET have been described in IC. Here, we genetically characterize the largest cohort of IC to date (33 cases) including 8 cases with focal or widespread invasive growth and 1 case with lymph node metastasis. Thirty-three cases of IC were analyzed by next-generation sequencing (NGS) using the FusionPlex Solid Tumor kit (ArcherDX). Identified gene fusions were confirmed using fluorescence in situ hybridization break-apart and fusion probes and an reverse transcription polymerase chain reaction designed specifically for the detected breakpoints. Ten cases of SDC were analyzed for comparison using NGS panels that detect mutations and fusion transcripts. NGS analysis detected an NCOA4-RET fusion transcript in 11 cases of intercalated duct-type IC joining exon 7 or 8 of NCOA4 gene and exon 12 of the RET gene. Eight cases of IC had an invasive growth pattern, including one with widespread invasion and lymph node metastasis. Three invasive ICs harbored an NCOA4-RET fusion transcript, while 1 case was negative, and 2 cases were not analyzable. In addition, a novel TRIM27-RET fusion transcript between exon 3 of TRIM27 and exon 12 of RET was identified in 2 cases of IC with apocrine features, and one of them displayed invasive growth. Two IC cases with invasive growth harbored novel fusions TUT1-ETV5 and KIAA1217-RET, respectively. A total of 42.4% of the cases in this series of IC harbored fusions involving RET. Such fusion transcripts were not detected in any of the 10 SDC cases. We have confirmed NCOA4-RET as a predominant fusion in intercalated duct-type IC, including 3 cases with invasive growth pattern. A novel finding in our series was a case of widely invasive intercalated duct-type IC, with a single lymph node metastasis that revealed an NCOA4-RET fusion transcript. We also demonstrated that a subset of apocrine ICs harbored a TRIM27-RET gene fusion, including one case with invasive growth. In contrast, neither NCOA4-RET nor TRIM27-RET fusions were detected in any tested SDCs. Thus, the distinct molecular findings in IC and SDC support that the tumors are separate malignant salivary tumor entities. The presence of tumor-type-specific NCOA4-RET or TRIM27-RET translocations in a subset of widely invasive carcinomas with intercalated duct-like immunoprofiles suggests that a recharacterization of IC including its redesignation as "intercalated duct carcinoma, invasive or noninvasive" may be appropriate.
- MeSH
- DNA vazebné proteiny genetika MeSH
- dospělí MeSH
- fúze genů * MeSH
- genetická predispozice k nemoci MeSH
- hybridizace in situ fluorescenční MeSH
- intraduktální neinfiltrující karcinom klasifikace genetika sekundární MeSH
- invazivní růst nádoru MeSH
- jaderné proteiny genetika MeSH
- koaktivátory jaderných receptorů genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- mladiství MeSH
- nádorové biomarkery genetika MeSH
- nádory slinných žláz klasifikace genetika patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- protoonkogenní proteiny c-ret genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- terminologie jako téma * MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství 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
- DNA vazebné proteiny MeSH
- jaderné proteiny MeSH
- koaktivátory jaderných receptorů MeSH
- nádorové biomarkery MeSH
- NCOA4 protein, human MeSH Prohlížeč
- protoonkogenní proteiny c-ret MeSH
- RET protein, human MeSH Prohlížeč
- TRIM27 protein, human MeSH Prohlížeč