RESUMO
AIMS: Identifying molecular alterations in the adenoma and carcinoma components within the same tumor would greatly contribute to understanding the neoplastic progression of early colorectal cancer. METHODS AND RESULTS: We examined somatic copy number alterations (SCNAs) and mutations involved in the adenoma and carcinoma components obtained from the same tumor in 46 cases of microsatellite-stable carcinoma in adenoma, using a genome-wide SNP array and gene mutation panel. In addition, we also performed hierarchical clustering to determine the SCNA frequencies in the tumors, resulting in stratification of the samples into two subgroups according to SCNA frequency. Subgroup 1 was characterized by multiple SCNAs and carcinoma components exclusively, while Subgroup 2 was characterized by a low frequency of SCNAs and both the adenoma and carcinoma components. The numbers of total genes and genes with gains were higher in the carcinoma than adenoma components. The three most frequent gains in both components were located at 1p36.33-1q44, 2p25.3-2q37.3, and 3p26.3-3q29. However, no candidate genes mapped to these regions. APC and KRAS mutations were common in both components, whereas the frequency of TP53 mutations was statistically higher in the carcinoma than adenoma component. However, TP53 mutations were not correlated with SCNA frequency. CONCLUSIONS: We suggest that considerable SCNAs and TP53 mutations are required for progression from adenoma to carcinoma within the same intramucosal neoplastic lesion.
Assuntos
Adenoma , Neoplasias Colorretais , Variações do Número de Cópias de DNA , Mutação , Humanos , Adenoma/genética , Adenoma/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Polimorfismo de Nucleotídeo Único , Carcinoma/genética , Carcinoma/patologia , Adulto , Dosagem de Genes , Proteína Supressora de Tumor p53/genéticaRESUMO
Secretory carcinoma is a rare, low-grade, special histological type of invasive breast carcinoma. Although it is the most common primary breast cancer in the pediatric population, most cases are diagnosed in adults, with a median age of 48 years (range 3 to 91 years). It most often presents as a painless and slowly growing palpable lump. Imaging findings are nonspecific. Secretory carcinomas have abundant periodic acid-Schiff positive intracytoplasmic and extracellular secretions on histopathology. Nearly all secretory carcinomas have mild to moderate nuclear pleomorphism with low mitotic activity. Over 80% (86/102) of secretory carcinomas display the translocation of t(12;15)(p13;q25), resulting in ETV6::NTRK3 gene fusion. Secretory carcinoma generally has an indolent course and has a better prognosis and overall survival than invasive breast carcinoma of no special type. A good prognosis is associated with age <20 years, tumor size <2 cm, and ≤3 axillary lymph node metastases. Metastases beyond the ipsilateral axillary lymph nodes are rare, with the most common sites involving the lung and liver. Except for the potential addition of targeted drug therapy for NTRK fusion-positive tumors, the treatment approach is otherwise similar to invasive breast carcinomas of similar receptor status.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico por imagem , Carcinoma/genética , Carcinoma/patologia , Carcinoma/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Mamografia , Idoso de 80 Anos ou mais , Mama/patologia , Mama/diagnóstico por imagem , Idoso , Prognóstico , AdolescenteRESUMO
Nasopharyngeal carcinoma (NPC) is often diagnosed at a very advanced stage due to its location and non-specific initial symptoms. Moreover, no clinically useful serological marker has been established so far for early detection of NPC. In this study, we have investigated the clinical significance of plasma Epstein-Barr virus DNA load along with interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) levels to evaluate if these three all together can be useful as a strong serological marker for early detection and prediction of treatment response in patients with NPC. Plasma EBV DNA load, IL-6 level, VEGF expressions were measured in 24 patients with NPC at presentation and various time points during and after treatment. There was a positive correlation between high plasma EBV DNA load with higher IL-6 and VEGF expression, which was closely associated with therapeutic response as well. Persistent or recurrent plasma EBV load with higher IL-6 and VEGF levels can potentially predict disease progression and may be useful to select patients for additional therapy and longer follow-up.
Assuntos
Carcinoma , DNA Viral , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Interleucina-6 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Fator A de Crescimento do Endotélio Vascular , Carga Viral , Humanos , Interleucina-6/sangue , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/diagnóstico , Herpesvirus Humano 4/genética , Feminino , Masculino , DNA Viral/sangue , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/sangue , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/diagnóstico , Adulto , Prognóstico , Carcinoma/virologia , Carcinoma/sangue , Carcinoma/diagnóstico , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/diagnóstico , Biomarcadores/sangue , Idoso , Plasma/virologiaRESUMO
Primary secretory carcinoma (SC) of the thyroid gland is a rare neoplasm, characterized by the presence of oncogenic ETV6::NTRK3 fusions, which are amenable to tropomyosin receptor kinase (TRK) inhibitor therapy. Despite its morphologic, immunophenotypic, and genetic similarities to SC of the salivary and mammary glands, diagnostic pitfalls may arise in differentiating from papillary thyroid carcinoma due to overlapping features such as papillary growth, nuclear irregularity, and variable expression of PAX8. Tumor misclassification may lead to delayed consideration of molecular testing and targeted therapy. A total of 13 cases of thyroid SC have been documented in the literature, indicating a tendency for advanced clinical presentation followed by a protracted clinical course, with most patients surviving until the end of the study period despite some experiencing recurrences. However, tumor-related mortality occurred in around 30% of cases, with the overall survival ranging from days to years, underscoring the variability in tumor behavior and the need for further research efforts. Among documented cases of thyroid SC, prognostic factors established for salivary SC have shown broad distributions, including a mitotic activity ranging from < 1 to 10 per 10 high-power fields and variable presence of necrosis, awaiting additional case experience to better elucidate their relevance in thyroid SC. We hereby present a 61-year-old female patient with widely metastatic thyroid SC treated with larotrectinib and provide an updated review of the literature on the molecular pathogenesis and clinicopathologic characteristics of this rare entity.
Assuntos
Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Feminino , Pessoa de Meia-Idade , Carcinoma/patologia , Carcinoma/genética , Proteínas de Fusão Oncogênica/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Variante 6 da Proteína do Fator de Translocação ETS , Receptor trkCRESUMO
BACKGROUND: Malignant neoplasms of the paranasal sinuses and nasal cavity are rare, comprising only 3% of all head and neck malignancies. Sinonasal undifferentiated carcinoma is a rare malignancy and an aggressive neoplasm that was clinic-pathologically distinct from other poorly differentiated malignancies of the nasal cavity and sinuses. The lesion is thought to originate from the epithelium, grows rapidly and invades nearby structures, often resulting in bony destruction while rapid progression of symptoms over weeks to months is characteristic. CASE DESCRIPTION: A 75-year-old man initially presented to ophthalmologist due to blurry vision and diplopia for 2 months. There was also progressive right eye swelling and pain for the past 12 months. Further image study revealed a right superomedial orbital mass with frontal/ethmoid sinus and frontal base extension, causing significant right eye gaze limitation, visual loss, ptosis, chemosis and exophthalmos. He was then transferred to neurosurgical clinic for further treatment where combined surgery was advocated to relieve the mass effect and also for pathology proof. Orbital roof/medial wall and frontal skull base were invaded and destroyed by the tumor. A bicoronal craniotomy was performed and extensive tumor removal was achieved except the orbital fossa due to difficult separation from the ocular muscle and optic nerve. Frontal base was reconstructed in a layered fashion to avoid cerebrospinal fluid (CSF) leakage and infection. He was sent to intensive care unit (ICU) for overnight observation where no further neurologic deterioration occurred. Instant orbital pain relief was noted with significantly decreased proptosis and improving visual acuity. Detailed pathological staining and molecular tests revealed a sinonasal undifferentiated carcinoma, adjuvant chemotherapy was arranged, followed by 30 cycles of radiotherapy. Slight disease progression was noted 12 months after the surgery, chemotherapy regimen was adjusted according to clinical response and he is still currently under regular adjuvant treatment. CONCLUSIONS: Sinonasal undifferentiated carcinoma typically carries a poor prognosis despite aggressive medical and surgical treatment, as it always presents at an advanced stage. Different combinations of chemotherapy, radiotherapy, radical surgical resection have been used to improve the outcome yet there is still not a universal treatment strategy. Early diagnosis, prompt treatment, and comprehensive medical care are crucial to achieve the best possible outcome for affected patients.
Assuntos
Carcinoma , Neoplasias dos Seios Paranasais , Humanos , Masculino , Idoso , Neoplasias dos Seios Paranasais/patologia , Prognóstico , Estesioneuroblastoma Olfatório , Neoplasias Orbitárias/patologia , Neoplasias do Seio MaxilarRESUMO
Zic family member ZIC4 is a transcription factor that has been shown to be silenced in several cancers. However, understanding the regulation and function of ZIC4 in pediatric choroid plexus tumors (CPTs) remained limited. This study employed data mining and bioinformatics analysis to investigate the DNA methylation status of ZIC4 in CPTs and its correlation with patient survival. Our results unveiled ZIC4 methylation as a segregating factor, dividing CPT cohorts into two clusters, with hyper-methylation linked to adverse prognosis. Hyper-methylation of ZIC4 was confirmed in a choroid plexus carcinoma-derived cell line (CCHE-45) by bisulfite sequencing. Furthermore, our study demonstrated that demethylating agent and a histone methyltransferase inhibitor could reverse ZIC4 silencing. RNA sequencing and proteomic analysis showed that ZIC4 over-expression influenced genes and proteins involved in immune response, antigen processing and presentation, endoplasmic reticulum stress, and metabolism. Functionally, re-expressing ZIC4 negatively impacted cell proliferation and migration. Ultimately, these findings underscore ZIC4 hyper-methylation as a prognostic marker in CPTs and shed light on potential mechanisms underlying its tumor suppressor role in CPC. This insight paves the way for novel therapeutic targets in treating aggressive CPTs.
Assuntos
Neoplasias do Plexo Corióideo , Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição , Humanos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Neoplasias do Plexo Corióideo/genética , Neoplasias do Plexo Corióideo/metabolismo , Neoplasias do Plexo Corióideo/patologia , Linhagem Celular Tumoral , Inativação Gênica , Carcinoma/genética , Carcinoma/metabolismo , Feminino , Masculino , Proliferação de Células/genética , Prognóstico , Criança , Lactente , Pré-Escolar , Genes Supressores de Tumor , Movimento Celular/genética , Proteínas do Tecido NervosoRESUMO
Polyploid Giant Cancer Cells (PGCCs) have been recognized as tumor cells that are resistant to anticancer therapies. However, it remains unclear whether their presence in the bloodstream can be consistently detected and utilized as a clinical marker to guide therapeutic anticancer regimens. To address these questions, we conducted a retrospective study involving 228 patients diagnosed with six different types of carcinomas (colon, gastric, NSCLC, breast, anal canal, kidney), with the majority of them (70%) being non-metastatic. Employing a highly sensitive liquid biopsy approach, ISET®, and cytopathological readout, we isolated and detected circulating PGCCs in the patients' blood samples. PGCCs were identified in 46 (20.18%) out of 228 patients, including in 14.47% of 152 non-metastatic and 29.85% of 67 metastatic cases. Patients were subsequently monitored for a mean follow up period of 44.74 months (95%CI: 33.39-55.79 months). Remarkably, the presence of circulating PGCCs emerged as a statistically significant indicator of poor overall survival. Our findings suggest that circulating PGCCs hold promise as a reliable prognostic indicator. They underscore the importance of further extensive investigations into the role of circulating PGCCs as a prognostic marker and the development of anti-PGCC therapeutic strategies to improve cancer management and patient survival.
Assuntos
Biomarcadores Tumorais , Células Gigantes , Células Neoplásicas Circulantes , Poliploidia , Humanos , Feminino , Masculino , Prognóstico , Biomarcadores Tumorais/sangue , Pessoa de Meia-Idade , Idoso , Células Neoplásicas Circulantes/patologia , Células Neoplásicas Circulantes/metabolismo , Células Gigantes/patologia , Estudos Retrospectivos , Adulto , Neoplasias/sangue , Neoplasias/patologia , Neoplasias/diagnóstico , Carcinoma/sangue , Carcinoma/patologia , Carcinoma/diagnóstico , Idoso de 80 Anos ou maisRESUMO
Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is a rare histological subtype of pancreatic ductal adenocarcinoma according to the World Health Organization classification of digestive system tumors. This subtype is exceptionally uncommon, accounting for less than 1% of pancreatic malignant tumors. This paper presents a rare case of a 62-year-old female patient diagnosed with UC-OGC. The patient initially presented with symptoms, including epigastric pain and the presence of an abdominal mass, which led to further investigation and the eventual diagnosis of this unusual and challenging form of pancreatic cancer.
Assuntos
Células Gigantes , Osteoclastos , Neoplasias Pancreáticas , Tomografia Computadorizada por Raios X , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Células Gigantes/patologia , Osteoclastos/patologia , Carcinoma/diagnóstico , Carcinoma/patologia , Imageamento por Ressonância MagnéticaRESUMO
Immunoproteasome is a specialized form of proteasome which plays a crucial role in antigen processing and presentation, and enhances immune responses against malignant cells. This review explores the role of immunoproteasome in the anti-tumor immune responses, including immune surveillance and modulation of the tumor microenvironment, as well as its potential as a target for cancer immunotherapy. Furthermore, we have also discussed the therapeutic potential of immunoproteasome inhibitors, strategies to enhance antigen presentation and combination therapies. The ongoing trials and case studies in urology, melanoma, lung, colorectal, and breast cancers have also been summarized. Finally, the challenges facing clinical translation of immunoproteasome-targeted therapies, such as toxicity and resistance mechanisms, and the future research directions have been addressed. This review underscores the significance of targeting the immunoproteasome in combination with other immunotherapies for solid tumors and its potential broader applications in other diseases.
Assuntos
Imunoterapia , Neoplasias , Complexo de Endopeptidases do Proteassoma , Microambiente Tumoral , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Imunoterapia/métodos , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/imunologia , Microambiente Tumoral/imunologia , Animais , Inibidores de Proteassoma/uso terapêutico , Inibidores de Proteassoma/farmacologia , Carcinoma/imunologia , Carcinoma/terapiaRESUMO
A 56-year-old female was referred to our service for management of a malignant salivary gland neoplasm with compromised margins that had been biopsied previously at another service. The patient reported a twenty-year history of a lesion in the oral cavity with progressive and exuberant growth over the past two years, associated with local pain and dyspnea. Physical examination revealed an erythematous, ulcerated, and hemorrhagic lesion measuring approximately 3 cm on the left soft palate and tonsillar pillar. Computed tomography revealed an expansile lesion in the topography of the left soft palate, growing predominantly toward the lumen of the nasopharynx and partially invading the left wall of this region. The patient underwent surgery and histopathologic examination revealed an infiltrative and aggressive epithelial neoplasia with large vacuolated and eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. The neoplastic cells were arranged in a solid, microcystic, tubular, and follicular pattern with eosinophilic luminal secretion. Mitotic figures were frequent and all margins were affected by the neoplasia. Morphologic and immunohistochemical features supported the diagnosis of secretory carcinoma, and the patient is currently being followed for further therapeutic intervention.
Assuntos
Neoplasias das Glândulas Salivares , Glândulas Salivares Menores , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Glândulas Salivares Menores/patologia , Carcinoma/patologia , Tomografia Computadorizada por Raios XRESUMO
Compared with re-radiotherapy or open surgery, endoscopic surgery for recurrent nasopharyngeal carcinoma has a better effect, which not only improves the overall survival rate, but also reduces serious complications, improves the quality of life and saves medical costs. With the advancement of modern surgical equipment and instruments, the deepening of anatomical research in the field of skull base, the improvement of surgical techniques and the development of multidisciplinary teamwork, the safety of endoscopic surgery and the rate of complete tumor resection will also increase. The indications for surgery are further expanded, and more patients with recurrent nasopharyngeal carcinoma benefit from endoscopic minimally invasive surgery. This article reviews the efficacy of endoscopic surgery for recurrent nasopharyngeal carcinoma, and then provides insights for the selection of clinical treatment strategies for recurrent nasopharyngeal carcinoma.
Assuntos
Carcinoma , Endoscopia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Humanos , Neoplasias Nasofaríngeas/cirurgia , Carcinoma Nasofaríngeo/cirurgia , Endoscopia/métodos , Recidiva Local de Neoplasia/cirurgia , Carcinoma/cirurgia , Resultado do Tratamento , Qualidade de VidaAssuntos
Herpesvirus Humano 4 , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/complicações , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/genética , Carcinoma/virologia , Carcinoma/genéticaRESUMO
OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) are complementary in staging of nasopharyngeal carcinoma (NPC). The combination of MRI and functional imaging from PET in PET/MR is promising in NPC management. Diagnostic performance of PET/CT and PET/MR was compared in 46 patients with histologically confirmed NPC under different disease scenarios, including primary non-metastatic cases, primary metastatic cases, recurrence and/or metastasis after treatment, and post-treatment follow-up cases. SUBJECTS AND METHODS: Forty-six patients underwent both PET/CT and PET/MR in the same day. Primary tumor extension into risk-stratified anatomic structures, retropharyngeal and cervical lymph node metastasis, distant metastasis and post-treatment follow-up results, were compared. RESULTS: For high-risk structures, PET/MR detected two more sides of tensor/levator veli palatine muscle involvement, one more case of clivus involvement, and ruled out 12 false-positive sides of prevertebral muscle involvement by PET/CT. For medium-risk structures, PET/MR detected four more sides of medial pterygoid muscle involvement. For low-risk structures, abnormal signal on massa lateralis atlantis was detected by PET/MR. PET/MR detected 14 more positive retropharyngeal lymph nodes and more liver micrometastases than PET/CT. Overall, PET/MR changed two patients' T staging. CONCLUSION: Positron emission tomography/MR outperforms PET/CT in delineating muscle, skull-base bone, and nodal involvement, and identifying liver micrometastases, may serve as a single-step staging modality for NPC.
Assuntos
Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/patologia , Adulto , Idoso , Compostos Radiofarmacêuticos , Carcinoma/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVE: We aimed to compare the clinical and endoscopic characteristics of sessile serrated lesions (SSLs) with dysplasia/carcinoma (SSLD/Cs) and SSLs without dysplasia in this systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and Cochrane Library databases and Clinicaltrials.gov were searched for relevant studies published up to August 28, 2023. The primary outcome was lesion size in SSLD/Cs and SSLs without dysplasia. The secondary outcomes included risk of dysplasia/carcinoma, morphology (classified based on the Paris classification), and lesion features such as mucus cap and nodules/protrusions in the two groups. RESULTS: Thirteen studies with 14 381 patients were included. The proportion of SSLD/Cs ≥10 mm was significantly higher than that of SSLs without dysplasia (odds ratio [OR] 3.82, 95% confidence interval [CI] 1.21-12.02, p = 0.02). There was no significant difference in the risk of dysplasia/carcinoma between the proximal (OR 0.80, 95% CI 0.57-1.14) and distal colon (OR 1.25, 95% CI 0.88-1.77, p = 0.21). The 0-Ip (OR 2.47, 95% CI 1.50-4.09) and 0-IIa + Is (OR 10.38, 95% CI 3.08-34.98) morphologies were more prevalent among SSLD/Cs, whereas the 0-IIa morphology (OR 0.38, 95% CI 0.22-0.65) was more prevalent among SSLs without dysplasia (all p < 0.001). Furthermore, mucus cap (OR 0.61, 95% CI 0.42-0.89, p = 0.01) was more common among SSLs without dysplasia, whereas nodules/protrusions (OR 7.80, 95% CI 3.07-19.85, p < 0.001) were more common in SSLD/Cs. CONCLUSION: SSLs >10 mm, 0-Ip or 0-IIa + Is morphologies, and those with nodules/protrusions are significantly associated with dysplasia/carcinoma.
Assuntos
Pólipos do Colo , Colonoscopia , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/patologia , Pólipos do Colo/patologia , Carcinoma/patologia , FemininoRESUMO
BACKGROUND: ETV6 gene rearrangement is the molecular hallmark of secretory carcinoma (SC), however; the nature, frequency, and clinical implications of atypical ETV6 signal patterns by fluorescence in situ hybridization (FISH) has not yet been systematically evaluated in salivary gland neoplasms. METHODS: The clinical, histopathologic, immunohistochemical and molecular features of seven salivary SCs, including four cases with atypical ETV6 FISH patterns, were retrospectively analyzed along with a critical appraisal of the literature on unbalanced ETV6 break-apart in SCs. RESULTS: The patients were four males and three females (31-70 years-old). Five presented with a painless neck mass and two patients with recurrent disease had a history of a previously diagnosed acinic cell carcinoma of the buccal mucosa. Histologically, there were varied combinations of microcystic, papillary, tubular, and solid patterns. All tumors were diffusely positive for S100 and/or SOX10, while 2 cases also showed luminal DOG1 staining. Rearrangement of the ETV6 locus was confirmed in 5/7 cases, of which 3 cases showed classic break-apart signals, 1 case further demonstrated duplication of the ETV6 5`end and the other loss of one copy of ETV6. Two cases harbored ETV6 deletion without rearrangement. Two of the 4 cases with atypical ETV6 FISH patterns represented recurrent tumors, one with widespread skeletal muscle involvement, bone and lymphovascular invasion. Surgical treatment resulted in gross-total resection in all 7 cases, with a median follow up of 9.5 months post-surgery for primary (n = 3) and recurrent disease (n = 1). CONCLUSION: Duplication of the distal/telomeric ETV6 probe represented the most common (26/40; 65%) variant ETV6 break-apart FISH pattern in salivary SC reported in the literature and appears indicative of an aggressive clinical course.
Assuntos
Variante 6 da Proteína do Fator de Translocação ETS , Proteínas Proto-Oncogênicas c-ets , Proteínas Repressoras , Neoplasias das Glândulas Salivares , Humanos , Masculino , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Proteínas Proto-Oncogênicas c-ets/genética , Feminino , Adulto , Idoso , Pessoa de Meia-Idade , Proteínas Repressoras/genética , Hibridização in Situ Fluorescente , Rearranjo Gênico , Carcinoma/genética , Carcinoma/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análiseRESUMO
Approximately 70% of treatment failures in nasopharyngeal carcinoma (NPC) patients are attributed to distant metastasis, yet the underlying mechanisms remain unclear. RNA 5-methylcytosine (m5C) is an emerging regulatory modification that controls gene expression and plays a critical role in tumor progression. However, there is little information on the potential roles of RNA m5C modification in NPC metastasis. In this study, we found that the m5C reader Aly/REF export factor (ALYREF) is significantly upregulated in NPC, whereby its high expression is associated with metastasis and poor prognosis. ALYREF overexpression was found to promote tumor metastasis of NPC cells in vitro and in vivo. Mechanistically, m5C-modified NOTCH1 mRNA was identified as a target of ALYREF. Moreover, ALYREF was found to upregulate NOTCH1 expression by enhancing its RNA stability in an m5C modification-dependent manner, thereby promoting the activation of the NOTCH signaling pathway and facilitating NPC metastasis. Overall, our data reveal the crucial role of ALYREF in NPC metastasis and provide a potential therapeutic target for NPC.
Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Metástase Neoplásica , Estabilidade de RNA , RNA Mensageiro , Receptor Notch1 , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Carcinoma/metabolismo , Carcinoma/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/metabolismo , Receptor Notch1/metabolismo , Receptor Notch1/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Transdução de Sinais , Regulação para Cima/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
This article describes a case of a man in his early 40s who was diagnosed with pulmonary pleomorphic carcinoma (PPC). PPCs are rare and aggressive forms of lung cancer. Chemotherapy is of limited efficacy. We present a case that has seemingly recurred shortly after adjuvant chemotherapy and immunotherapy following an R0 resection for localised disease. Biopsy however was negative for recurrence. PPCs may bear actionable mutations and tyrosine kinase inhibitors may be used when appropriate. Immunotherapy with or without chemotherapy is emerging as the mainstay for metastatic disease despite a lack of evidence from randomised clinical trials.
Assuntos
Neoplasias Pulmonares , Humanos , Masculino , Neoplasias Pulmonares/patologia , Adulto , Recidiva Local de Neoplasia , Quimioterapia Adjuvante , Carcinoma/patologia , Carcinoma/terapia , Imunoterapia/métodosRESUMO
Mouse orthotopic xenograft tumor models are commonly employed in studies investigating the mechanisms underlying the development and progression of tumors and their preclinical treatment. However, the unavailability of mature and visualized orthotopic xenograft models of nasopharyngeal carcinoma limits the development of treatment strategies for this cancer. The aim of this study was to provide a simple and reliable method for building an orthotopic xenograft model of nasopharyngeal carcinoma. Human nasopharyngeal carcinoma (C666-1-luc) cells, stably expressing the firefly luciferase gene, were injected subcutaneously into the right axilla of BALB/C nude mice. Four weeks later, the resulting subcutaneous tumors were cut into small blocks and grafted into the nasopharynx of immunodeficient BALB/C nude mice to induce tumor formation. Tumor growth was monitored by bioluminescence imaging and small animal magnetic resonance imaging (MRI). The expression of histological and immunological antigens associated with orthotopic xenograft nasopharyngeal carcinoma was analyzed by tissue section analysis and immunohistochemistry (IHC). A visualized orthotopic xenograft nasopharyngeal carcinoma model was successfully developed in this study. Luminescence signal detection, micro-MRI, and hematoxylin and eosin staining revealed the successful growth of tumors in the nasopharynx of the nude mice. Moreover, IHC analysis detected cytokeratin (CK), CK5/6, P40, and P63 expression in the orthotopic tumors, consistent with the reported expression of these antigens in human nasopharyngeal tumors. This study established a reproducible, visual, and less lethal orthotopic xenograft model of nasopharyngeal carcinoma, providing a platform for preclinical research.