RÉSUMÉ
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.
Sujet(s)
Marqueurs biologiques tumoraux , Cellules géantes , Cellules tumorales circulantes , Polyploïdie , Humains , Femelle , Mâle , Pronostic , Marqueurs biologiques tumoraux/sang , Adulte d'âge moyen , Sujet âgé , Cellules tumorales circulantes/anatomopathologie , Cellules tumorales circulantes/métabolisme , Cellules géantes/anatomopathologie , Études rétrospectives , Adulte , Tumeurs/sang , Tumeurs/anatomopathologie , Tumeurs/diagnostic , Carcinomes/sang , Carcinomes/anatomopathologie , Carcinomes/diagnostic , Sujet âgé de 80 ans ou plusRÉSUMÉ
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.
Sujet(s)
Tumeurs des glandes salivaires , Glandes salivaires mineures , Humains , Femelle , Adulte d'âge moyen , Tumeurs des glandes salivaires/anatomopathologie , Tumeurs des glandes salivaires/diagnostic , Glandes salivaires mineures/anatomopathologie , Carcinomes/anatomopathologie , TomodensitométrieRÉSUMÉ
Salivary glands' neoplasms are hard to diagnose and present a complex etiology. However, several viruses have been detected in these neoplasms, such as HCMV, which can play a role in certain cancers through oncomodulation. The co-infections between HCMV with betaherpesviruses (HHV-6 and HHV-7) and polyomaviruses (JCV and BKV) has been investigated. The aim of the current study is to describe the frequency of HCMV and co-infections in patients presenting neoplastic and non-neoplastic lesions, including in the salivary gland. Multiplex quantitative polymerase chain reaction was used for betaherpesvirus and polyomavirus quantification purposes after DNA extraction. In total, 50.7% of the 67 analyzed samples were mucocele, 40.3% were adenoma pleomorphic, and 8.9% were mucoepidermoid carcinoma. Overall, 20.9% of samples presented triple-infections with HCMV/HHV-6/HHV-7, whereas 9.0% were co-infections with HCMV/HHV-6 and HCMV/HHV-7. The largest number of co-infections was detected in pleomorphic adenoma cases. All samples tested negative for polyomaviruses, such as BKV and JCV. It was possible to conclude that HCMV can be abundant in salivary gland lesions. A high viral load can be useful to help better understand the etiological role played by viruses in these lesions. A lack of JCV and BKV in the samples analyzed herein does not rule out the involvement of these viruses in one or more salivary gland lesion subtypes.
Sujet(s)
Co-infection , Infections à cytomégalovirus , Cytomegalovirus , Tumeurs des glandes salivaires , Glandes salivaires , Humains , Co-infection/virologie , Infections à cytomégalovirus/virologie , Infections à cytomégalovirus/diagnostic , Cytomegalovirus/génétique , Cytomegalovirus/isolement et purification , Mâle , Femelle , Tumeurs des glandes salivaires/virologie , Adulte d'âge moyen , Adulte , Sujet âgé , Glandes salivaires/virologie , Glandes salivaires/anatomopathologie , Adénomes/virologie , Sujet âgé de 80 ans ou plus , Carcinomes/virologie , ADN viral/génétique , ADN viral/analyse , Jeune adulte , AdolescentRÉSUMÉ
Equine bladder neoplasms are rare. This report aimed to describe the clinical signs and treatment of urothelial carcinoma (UC) in a mule. Cystoscopy of a 20-year-old female mule with a one-week history of hematuria and anemia revealed vascular congestion in the mucosa and an intraluminal, pedunculated mass in the dorsal bladder region. Histopathological examination revealed UC. Initial therapy consisted of four weekly cystoscopic guided injections of fluorouracil. At the fourth chemotherapy session, a paler and more friable tumor mass was observed. Consequently, we opted to surgically remove it during cystoscopy. Following mass excision, patient comfort, gross appearance of urine, and the hematocrit returned to normal. Repeat cystoscopy examinations revealed no gross appearance of tumor recurrence 18 months after treatment. Bladder neoplasms clinically resemble urolithiasis and cystitis and should be considered a differential diagnosis in cases of anemia and hematuria.
Sujet(s)
Tumeurs de la vessie urinaire , Femelle , Tumeurs de la vessie urinaire/diagnostic , Tumeurs de la vessie urinaire/anatomopathologie , Tumeurs de la vessie urinaire/thérapie , Animaux , Carcinomes/diagnostic , Carcinomes/anatomopathologieRÉSUMÉ
Genomic instability is an important biomarker in the progression of cervical carcinoma. DBD-FISH (DNA breakage detection-fluorescence in situ hybridization) is a sensitive method that detects strand breaks, alkali-labile sites, and incomplete DNA excision repair in cells of the cervical epithelium. This technique integrates the microgel immersion of cells from a vaginal lesion scraping and the DNA unwinding treatment with the capacity of FISH integrated into digital image analysis. Cells captured within an agarose matrix are lysed and submerged in an alkaline unwinding solution that generates single-stranded DNA motifs at the ends of internal DNA strand breaks. After neutralization, the microgel is dehydrated and the cells are incubated with DNA-labeled probes. The quantity of a hybridized probe at a target sequence corresponds to the measure of the single-stranded DNA produced during the unwinding step, which is equivalent to the degree of local DNA breakage. DNA damage does not show uniformly throughout the entire DNA of a cell; rather, it is confined to specific chromosomal sites. In this chapter, an overview of the technique is supplied, focusing on its ability for assessing the association between DNA damage in specific sequences and in the progressive stages of cervical carcinoma.
Sujet(s)
Carcinomes , Microgels , Tumeurs du col de l'utérus , Femelle , Humains , ADN , Altération de l'ADN , Sondes d'ADN/génétique , ADN simple brin , Hybridation fluorescente in situ/méthodes , Tumeurs du col de l'utérus/génétique , Tumeurs du col de l'utérus/anatomopathologieRÉSUMÉ
Otariid gammaherpesvirus 1 (OtGHV1) is associated with high rates of urogenital carcinoma in free-ranging California sea lions (Zalophus californianus; CSL), and until recently was reported only in the Northern Hemisphere. The objective of this study was to survey free-ranging South American sea lions (Otaria byronia; SASL) and South American fur seals (Arctocephalus australis: SAFS) in Punta San Juan, Peru for OtGHV1 and to determine prevalence characteristics. Twenty-one percent (14/67) of urogenital swabs collected over three years (2011, 2014, 2015) from live pinnipeds of both species tested positive with a pan-herpesvirus conventional PCR. Sequencing of SAFS amplicons revealed 100% homology to OtGHV1 at the DNA polymerase, glycoprotein B, and viral bcl2-like genes. Sequencing of SASL amplicons revealed a novel related virus, herein called Otariid gammaherpesvirus 8 (OtGHV8). For comparison of sample sites, urogenital, conjunctival, and oropharyngeal swabs collected from 136 live pinnipeds of both species at Punta San Juan between 2011-2018 were then assayed using quantitative PCR for a segment of the OtGHV1/8 DNA polymerase gene using a qPCR assay now determined to cross-react between the two viruses. In total, across both species, 38.6% (51/132) of urogenital swabs, 5.6% (4/71) of conjunctival swabs, and 1.1% (1/90) of oropharyngeal swabs were positive for OtGHV1/8, with SASL only positive on urogenital swabs. Results from SASL were complicated by the finding of OtGHV8, necessitating further study to determine prevalence of OtGHV1 versus OtGHV8 using an alternate assay. Results from SAFS suggest a potential relationship between OtGHV1 in SAFS and CSL. Though necropsy surveillance in SAFS is very limited, geographic patterns of OtGHV1-associated urogenital carcinoma in CSL and the tendency of herpesviruses to cause more detrimental disease in aberrant hosts suggests that it is possible that SAFS may be the definitive host of OtGHV1, which gives further insight into the diversity and phyogeography of this clade of related gammaherpesviruses.
Sujet(s)
Pinnipedia , Carcinomes , Otaries à fourrure , Gammaherpesvirinae , Herpesviridae , Lions de mer , Animaux , Humains , Prévalence , Gammaherpesvirinae/génétique , Pérou/épidémiologie , DNA-directed DNA polymeraseRÉSUMÉ
OBJECTIVE: To identify the differences between early- (EOCRC) and late-onset colorectal cancer (LOCRC), and to evaluate the determinants of one-year all-cause mortality among advanced-stage patients. METHODS: A retrospective cohort study was carried out. CRC patients ≥ 18 years old were included. Chi-Square test was applied to compare both groups. Uni- and multivariate regressions were performed to evaluate the determinants of one-year all-cause mortality in all advanced-stage patients regardless of age of onset. RESULTS: A total of 416 patients were enrolled; 53.1 % were female. Ninety cases (21.6 %) had EOCRC and 326 (78.4 %) had LOCRC. EOCRC cases were predominantly sporadic (88.9 %). Histology of carcinoma other than adenocarcinoma (p= 0.044) and rectum tumors (p= 0.039) were more prevalent in EOCRC. LOCRC patients were more likely to have smoking history (p < 0.001) and right colon tumors (p = 0.039). Alcohol consumption history (odds ratio [OR]: 3.375, 95 %CI: 1.022-11.150) and stage IV (OR: 12.632, 95 %CI: 3.506-45.513) were associated with higher one-year all-cause mortality among advanced-stage patients, the opposite was noted with left colon tumors (OR: 0.045, 95 %CI: 0.003-0.588). CONCLUSION: EOCRC was predominantly sporadic and had more cases of uncommon histological subtypes and rectal tumors. LOCRC was characterized by a higher prevalence of smoking history. Multivariate regression revealed an association between higher one-year all-cause mortality and alcohol consumption history and stage IV in advanced-stage patients. CRC exhibited differences based on age of onset. The evaluated factors associated with CRC mortality provide valuable insights for healthcare professionals, emphasizing the importance of adequate clinical assessment and early CRC diagnosis.
Sujet(s)
Âge de début , Tumeurs colorectales , Tumeurs colorectales/complications , Tumeurs colorectales/épidémiologie , Tumeurs colorectales/mortalité , Tumeurs colorectales/anatomopathologie , Humains , Colombie , Études rétrospectives , Études de cohortes , Mâle , Femelle , Adulte , Adulte d'âge moyen , Sujet âgé , Stadification tumorale , Comorbidité , Carcinomes/épidémiologie , Carcinomes/mortalité , Carcinomes/anatomopathologie , Adénocarcinome/épidémiologie , Adénocarcinome/mortalité , Adénocarcinome/anatomopathologie , Fumer/épidémiologieRÉSUMÉ
BACKGROUND: Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. METHOD: A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. RESULTS: Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. CONCLUSION: Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.
Sujet(s)
Carcinomes , Lupus érythémateux disséminé , Enfant , Femelle , Humains , Mâle , Jeune adulte , Âge de début , Carcinomes/complications , Lupus érythémateux disséminé/complications , Études rétrospectivesRÉSUMÉ
BACKGROUND: Salivary gland carcinomas (SGCs) are a rare group of malignant neoplasms of the head and neck region. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been associated with the control biological process and oncogenic mechanism by the regulation of gene expression at the post-transcriptional level. Recent evidence has suggested that miRNA expression may play a role in the tumorigenesis and carcinogenesis process in SGCs. METHODS: This review provides a comprehensive literature review of the role of miRNAs expression in SGCs focusing on the diagnostic, prognostic, and therapeutic applications. RESULTS: In this review, numerous dysregulated miRNAs have demonstrated an oncogenic and suppressor role in SGCs. CONCLUSION: In the future, these miRNAs may eventually constitute useful diagnostic and prognostic biomarkers that may lead to a better understanding of SGCs oncogenesis. Additionally, the development of therapeutic agents based on miRNAs may be a promising target in SGC treatment.
Sujet(s)
Carcinomes , microARN , Tumeurs des glandes salivaires , Humains , microARN/génétique , Marqueurs biologiques , Tumeurs des glandes salivaires/anatomopathologie , Carcinogenèse/génétique , Transformation cellulaire néoplasique , Pronostic , Glandes salivaires/métabolisme , Marqueurs biologiques tumoraux/génétiqueRÉSUMÉ
NSD3 (nuclear receptor-binding SET domain protein 3) is a member of the NSD histone methyltransferase family of proteins. In recent years, it has been identified as a potential oncogene in certain types of cancer. The NSD3 gene encodes three isoforms, the long version (NSD3L), a short version (NSD3S) and the WHISTLE isoforms. Importantly, the NSD3S isoform corresponds to the N-terminal region of the full-length protein, lacking the methyltransferase domain. The chromosomal location of NSD3 is frequently amplified across cancer types, such as breast, lung, and colon, among others. Recently, this amplification has been correlated to a chromothripsis event, that could explain the different NSD3 alterations found in cancer. The fusion proteins containing NSD3 have also been reported in leukemia (NSD3-NUP98), and in NUT (nuclear protein of the testis) midline carcinoma (NSD3-NUT). Its role as an oncogene has been described by modulating different cancer pathways through its methyltransferase activity, or the short isoform of the protein, through protein interactions. Specifically, in this review we will focus on the functions that have been characterized as methyltransferase dependent, and those that have been correlated with the expression of the NSD3S isoform. There is evidence that both the NSD3L and NSD3S isoforms are relevant for cancer progression, establishing NSD3 as a therapeutic target. However, further functional studies are needed to differentiate NSD3 oncogenic activity as dependent or independent of the catalytic domain of the protein, as well as the contribution of each isoform and its clinical significance in cancer progression.
Sujet(s)
Histone-lysine N-methyltransferase , Tumeurs , Protéines nucléaires , Humains , Mâle , Carcinomes/enzymologie , Leucémies/enzymologie , Oncogènes , Isoformes de protéines/génétique , Histone-lysine N-methyltransferase/métabolisme , Protéines nucléaires/métabolisme , Tumeurs/enzymologie , Tumeurs/anatomopathologieRÉSUMÉ
OBJECTIVE: To evaluate the immunoexpression profile for CD8, CD3, CD20 and CD68 in the process and carcinogenesis of Carcinoma of the vermilion lip. METHODS: Average cell count with positive expression for CD3, CD8, CD20 and CD68. The CD8/CD3 ratio calculated in the region was based on the percentage of positive cells in a total of malignant cells. Kruska-Wallis/Dunn, Mann-Whitney and Spearman correlation tests (SPSS, pâ¯<â¯0.05) were used. RESULTS: In the Aquitic Cheilitis samples, there was an increase in intraepithelial CD8+ and CD68+. In LSCCs, there was an increase in peritumoral and intratumoral CD3+, CD8+, CD20+ and CD68+ cells. In peritumoral LSCC, CD3+ and CD8+ showed a direct correlation (pâ¯=â¯0.004), and CD68+ and CD8+ (pâ¯=â¯0.017). In the intraepithelial region, CD8+ correlated with CD20+ (pâ¯=â¯0.014) and CD68+ (pâ¯=â¯0.013). In the CAs, CD3 (pâ¯<â¯0.001) and CD8 (pâ¯=â¯0.025) correlated intraepithelial and subepithelial. In LSCC CD3+ (pâ¯=â¯0.002), CD8+ (pâ¯=â¯0.001) and CD68+ (pâ¯=â¯0.030) had intra and peritumoral correlation. CONCLUSION: CD68+ is the first interacting cell with the greatest capacity to migrate to the tumor and interact with CD3, CD8 and CD20. Apparently, CD20 affects perineural invasion. LEVEL OF EVIDENCE: Level 2.
Sujet(s)
Carcinomes , Lèvre , Humains , Lymphocytes T CD8+ , Carcinogenèse , Macrophages , PronosticRÉSUMÉ
BACKGROUND: Ameloblastoma and ameloblastic carcinoma are epithelial odontogenic tumors that can be morphologically similar. In the present study, we evaluated the DNA content and Ki-67 index in the two tumors. METHODS: The paraffin blocks of the tumors were selected to obtain sections for the immunohistochemical reactions and preparation of the cell suspension for acquisition in a flow cytometer. The Random Forest package of the R software was used to verify the contribution of each variable to classify lesions into ameloblastoma or ameloblastic carcinoma. RESULTS: Thirty-two ameloblastoma and five ameloblastic carcinoma were included in the study. In our sample, we did not find statistically significant differences in Ki-67 labeling rates. A higher fraction of cells in 2c (G1) was correlated with the diagnosis of ameloblastoma, whereas higher rates of 5c-exceeding rate (5cER) were correlated with ameloblastic carcinoma. The Random Forest model highlighted histopathological findings and parameters of DNA ploidy study as important features for distinguishing ameloblastoma from ameloblastic carcinoma. CONCLUSION: Our findings suggest that the parameters of the DNA ploidy study can be ancillary tools in the classification of ameloblastoma and ameloblastic carcinoma.
Sujet(s)
Améloblastome , Carcinomes , Tumeurs odontogènes , Humains , Améloblastome/diagnostic , Améloblastome/génétique , Améloblastome/anatomopathologie , Antigène KI-67/génétique , Tumeurs odontogènes/génétique , Carcinomes/anatomopathologie , Ploïdies , ADNRÉSUMÉ
Angiogenesis is considered one of the hallmarks of cancer, assisting tumor progression and metastasis. The mesoionic compound, MI-D, can induce cell death and provoke cytoskeletal and metabolic changes in cancer cells. Using in vitro and in vivo models, this study aimed to evaluate the effects of MI-D on the viability of human endothelial cells (EC) and its ability to inhibit tumor-induced angiogenesis induced by tumoral cells. For in vitro analysis, colon carcinoma (HT29) and endothelial (EA.hy926) cells were used as the tumoral and angiogenesis models, respectively. To evaluate cytotoxicity, methylene blue viability stain and annexin-V/7AAD tests were performed with both cell types. For the angiogenesis experiments, scratch wound healing and capillary tube-like formation assays were performed with the EC. The in vivo tests were performed with the chorioallantoic membrane (HET-CAM) methodology, wherein gelatin sponge implants containing MI-D (5, 25, and 50 µM), HT29 cells, or both were grafted in the CAM. Our data showed that MI-D induced apoptosis in both endothelial and colon carcinoma cells, with a strong cytotoxic effect on the tumoral lineage. The drug inhibited the EC's migration and capillary-like structure formation in vitro. In the HET-CAM assays, MI-D reduced the number of blood vessels in the membrane when grafted alone and accompanied by tumor cells. In this study, MI-D interfered in important steps of angiogenesis, such as maintenance of endothelial cell viability, migration, formation of capillary-like structures, as well tumor-induced neovascularization, reinforcing the hypothesis that MI-D might act as an inhibitor of angiogenesis, and a potential antitumor agent.
Sujet(s)
Antinéoplasiques , Carcinomes , Humains , Cellules endothéliales , Angiogenesis , Inhibiteurs de l'angiogenèse/pharmacologie , Inhibiteurs de l'angiogenèse/usage thérapeutique , Mouvement cellulaire , Néovascularisation pathologique/traitement médicamenteux , Néovascularisation pathologique/métabolisme , Antinéoplasiques/usage thérapeutique , Carcinomes/métabolisme , Cellules endothéliales de la veine ombilicale humaine , Prolifération cellulaireRÉSUMÉ
Warthin's tumor (WT) is a benign and frequent salivary gland tumor primarily affecting the parotid gland. In some cases, this tumor can involve the extra parotid region and affect cervical lymph nodes. Fine-needle aspiration can be the first step in the diagnostic approach to lymphadenopathy; however, specimens from intra-nodal WT can present a potential pitfall, leading to a misdiagnosis of metastasis. Here, we report an unusual case of a patient with bilateral WT in parotid lymph nodes misdiagnosed as metastases. In addition, we highlight the cytopathological aspects of WT to alert cytopathologists about this challenging diagnosis.
Sujet(s)
Adénolymphome , Carcinomes , Tumeurs de la parotide , Humains , Tumeurs de la parotide/diagnostic , Tumeurs de la parotide/anatomopathologie , Adénolymphome/diagnostic , Adénolymphome/anatomopathologie , Carcinomes/anatomopathologie , Glande parotide/anatomopathologie , Noeuds lymphatiques/anatomopathologieRÉSUMÉ
PURPOSE: Patients with clear cell renal cell carcinoma (ccRCC) might develop metastasis after surgery with curative intent. We aimed to characterize the expression levels of microRNAs in the urine (UmiRNAs) of patients before and after nephrectomy to determine the impact of UmiRNAs expression in the emergence of metastases. METHODS: We prospectively collected pre- and post-nephrectomy urine samples from 117 patients with clinically localized and locally advanced ccRCC. UmiRNAs were extracted, purified, and measured using RT-PCR. Relative quantifications (RQ) of 137 UmiRNAs were calculated through 2-∆∆ method. The post-surgery/pre-surgery RQs ratio represented the magnitude of the expression levels of the UmiRNAs. The association of UmiRNA expression and the development of distant metastases was tested with Cox regression model. RESULTS: Five UmiRNAs (miR-191-5p, miR-324-3p, miR-186-5p, miR-93-5p, miR-30b-5p) levels were upregulated before nephrectomy (p < .05). This conferred a 2- to 4-fold increased risk of metastasis, with miR-191-5p showing the most significant association with this endpoint (HR = 4.16, 95% CI = 1.38-12.58, p = .011). In a multivariate model stratified with stage and Fuhrman grade, we found that miR-191-5p, miR-324-3p, and miR-186-5p exhibited a strong association with metastasis development in patients with pathological T3 (pT3) tumors. Enrichment analysis with the most differentially expressed UmiRNAs showed that these UmiRNAs targeted genes that regulate cell survival and proliferation. CONCLUSION: Our study indicated UmiR-191-5p, UmiR-324-3p, and UmiR-186-5p are potential markers to predict the development of metastasis, particularly in pT3 patients. PATIENT SUMMARY: We compared changes of UmiRNAs expression detected pre- and postnephrectomy of patients with ccRCC. Our findings suggest that UmiRNA expression likely reflects tumor-specific changes that can be promising to predict the metastasis development, particularly in patients with non-metastatic locally advanced ccRCC. If confirmed, these findings may be useful for surveillance protocols for adjuvant therapy protocols.
Sujet(s)
Néphrocarcinome , Carcinomes , Tumeurs du rein , microARN , Humains , Néphrocarcinome/génétique , Néphrocarcinome/chirurgie , Néphrocarcinome/anatomopathologie , microARN/génétique , Tumeurs du rein/génétique , Tumeurs du rein/chirurgie , Tumeurs du rein/anatomopathologie , Néphrectomie , Modèles des risques proportionnels , Carcinomes/génétique , Régulation de l'expression des gènes tumoraux , Marqueurs biologiques tumoraux/génétiqueRÉSUMÉ
OBJECTIVES: Nasopharyngeal carcinoma (NPC) is an aggressive epithelial cancer. The expression of miR-186 is decreased in a variety of malignancies and can promote the invasion and metastasis of cancer cells. This study aimed to explore the role and possible mechanism of miR-186 in the metastasis and epithelial-mesenchymal transformation (EMT) of NPC. METHODS: The expression of miR-186 in NPC tissues and cells was detected by RT-PCR. Then, miR-186 mimic was used to transfect NPC cell lines C666-1 and CNE-2, and cell activity, invasion and migration were detected by CCK8, transwell and scratch assay, respectively. The expression of EMT-related proteins was analyzed by western blotting analysis. The binding relationship between miR-186 and target gene Zinc Finger E-Box Binding Homeobox 1 (ZEB1) was confirmed by double luciferase assay. RESULTS: The expression of miR-186 in NPC was significantly decreased, and transfection of miR-186 mimic could significantly inhibit the cell activity, invasion, and migration, and regulate the protein expressions of E-cadherin, N-cadherin and vimentin in C666-1 and CNE-2 cells. Further experiments confirmed that miR-186 could directly target ZEB1 and negatively regulate its expression. In addition, ZEB1 has been confirmed to be highly expressed in NPC, and inhibition of ZEB1 could inhibit the activity, invasion, metastasis and EMT of NPC cells. And co-transfection of miR-186 mimic and si-ZEB1 could further inhibit the proliferation and metastasis of NPC. CONCLUSION: miR-186 may inhibit the proliferation, metastasis and EMT of NPC by targeting ZEB1, and the miR-186/ZEB1 axis plays an important role in NPC.
Sujet(s)
Carcinomes , microARN , Tumeurs du rhinopharynx , Humains , Cancer du nasopharynx/anatomopathologie , microARN/génétique , microARN/métabolisme , Lignée cellulaire tumorale , Carcinomes/génétique , Carcinomes/anatomopathologie , Transition épithélio-mésenchymateuse/génétique , Tumeurs du rhinopharynx/génétique , Tumeurs du rhinopharynx/anatomopathologie , Régulation de l'expression des gènes tumoraux/génétique , Prolifération cellulaire , Invasion tumorale/génétique , Facteur de transcription Zeb1/génétique , Facteur de transcription Zeb1/métabolismeRÉSUMÉ
B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.
Sujet(s)
Tumeurs du sein , Carcinome à cellules acineuses , Carcinome adénoïde kystique , Carcinome mucoépidermoïde , Carcinomes , Tumeurs des glandes salivaires , Humains , Femelle , Carcinome adénoïde kystique/anatomopathologie , Pronostic , Carcinome à cellules acineuses/anatomopathologie , Tumeurs des glandes salivaires/anatomopathologie , Carcinome mucoépidermoïde/anatomopathologie , Carcinomes/anatomopathologie , Glandes salivaires/composition chimique , Glandes salivaires/métabolisme , Glandes salivaires/anatomopathologie , Marqueurs biologiques tumoraux/analyseRÉSUMÉ
O carcinoma mioepitelial é uma doença incomum que tem origem majoritariamente nas glândulas salivares. A sua ocorrência no pulmão é um achado extremamente raro e acredita-se ter origem nas glândulas brônquicas submucosas do trato respiratório inferior. Marcado pela sua grande diversidade citológica e arquitetônica, que recapitula as características celulares e imunofenotípicas das células mioepiteliais, é uma neoplasia tipicamente de alto grau e comportamento agressivo, sendo facilmente confundida com outras neoplasias torácicas e representando um desafio diagnóstico. Não há diretrizes estabelecidas para o tratamento a cirurgia parece ser a melhor alternativa, uma vez que o papel da quimioterapia e radioterapia é incerto. Este é um estudo observacional descritivo retrospectivo em modelo de relato de caso realizado através de avaliação do prontuário de um paciente com diagnóstico de carcinoma mioepitelial pulmonar matriculado no INCA no período de setembro a novembro de 2023. Para a discussão do tema, esse trabalho também contou com uma revisão da literatura médica utilizando os dados obtidos através das plataformas Pubmed, Scielo e Google acadêmico. Após extensa pesquisa, encontramos apenas 21 casos publicados de carcinoma mioepitelial pulmonar e acreditamos que a dificuldade técnica envolvida no diagnóstico, sobreposta as barreiras de tecnologia e conhecimento do passado, possam ter contribuído para subestimar o número de casos dessa neoplasia. Nesse contexto, o carcinoma mioepitelial pulmonar primário deve ser incluído no diagnóstico diferencial das neoplasias torácicas. Embora mais estudos sejam necessários para esclarecimento dos aspectos moleculares e estratégias terapêuticas, o tratamento individualizado é uma estratégia clínica promissora para neoplasias torácicas em geral e os eventos moleculares subjacentes devem ser investigados para encontrar os potenciais alvos terapêuticos
Myoepithelial carcinoma is an uncommon disease that originates mainly in the salivary glands. Its occurrence in the lung is an extremely rare finding and is believed to originate from the submucosal bronchial glands of the lower respiratory tract. Marked by its great histological and architectural diversity, which recapitulates the cellular and immunophenotypic characteristics of myoepithelial cells, it is a typically high-grade neoplasm with aggressive behavior, being easily confused with other thoracic neoplasms and representing a diagnostic challenge. There are no established guidelines for treatment upfront surgery appears to be the best alternative, as the role of chemotherapy and radiotherapy is uncertain. This is a retrospective descriptive observational study using a case report model carried out by evaluating the medical records of a patient diagnosed with pulmonary myoepithelial carcinoma enrolled at INCA from september to november 2023. To discuss the topic, this work also included a review of the medical literature using data obtained from Pubmed, Scielo and Google Scholar. We found Only 21 published cases of pulmonary myoepithelial carcinoma on research platforms and we believe that the technical difficulty involved in diagnosis, combined with technology and knowledge barriers from the past, may have contributed to underestimating the number of cases of this neoplasm. In this context, primary pulmonary myoepithelial carcinoma should be included in the differential diagnosis of thoracic neoplasms. Although further studies are needed to clarify the molecular aspects and therapeutic strategies, individualized treatment is a promising clinical strategy for thoracic neoplasms in general and the underlying molecular events must be investigated to find potential therapeutic targets.
Sujet(s)
Humains , Mâle , Carcinomes , Myoépithéliome , Tumeurs du poumon , Biologie moléculaireRÉSUMÉ
O Carcinoma Odontogêncio de Células Claras (COCC), é uma neoplasia rara descrita pela primeira vez por Hansen em 1985. Inicialmente categorizado como benigno, foi reclassificado como maligno no ano de 2005 pela OMS, devido ao seu comportamento localmente agressivo, alta taxa de recidiva local e potencial, metástase a distância. O presente caso relata a abordagem terapêutica aplicada ao tratamento do COCC avançado de mandíbula em uma paciente de 23 anos, do sexo feminino. A tomografia evidenciava uma volumosa massa osteodestrutiva mandibular com cerca de 10,6 x 7,2 cm, que comprometia difusamente o arco central e ramos horizontais. Foi realizada mandibulectomia de arco central estendida aos ramos horizontais bilaterais e esvaziamento cervical supraomo-hioideo bilateral associado à reconstrução microcirúrgica com retalho de fíbula esquerda, seguida de radioterapia adjuvante na dose de 66Gy. Paciente completou seis meses de seguimento, sem evidência de doença e com excelente resultado estético e funcional, alimentando-se pela via oral e com boa fonação.
Clear cell odontogenic carcinoma (COCC) is a rare neoplasm first described by Hansen in 1985. Initially categorized as benign, it was reclassified as malignant in 2005 by the WHO, due to its locally aggressive behavior and high recurrence rate. local and potential, distant metastasis. The present case reports the therapeutic approach applied to the treatment of advanced COCC of the mandible in a 23-year-old female patient. The tomography showed a large mandibular osteodestructive mass measuring approximately 10.6 x 7.2 cm, which diffusely affected the central arch and horizontal branches. A central arch mandibulectomy extended to the bilateral horizontal branches and bilateral supra omohyoid neck dissection associated with microsurgical reconstruction with a left fibula flap were performed, followed by adjuvant radiotherapy at a dose of 66 Gy. The patient completed six months of follow-up, with no evidence of disease and excellent aesthetic and functional results, eating orally and with good speech