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1.
Cytopathology ; 35(3): 344-349, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38351503

RESUMEN

Cytological specimens play a pivotal role in head and neck nodule/mass work up and diagnoses. The specimens´ importance has grown with the onset of personalized medicine and the routine use of molecular markers in the diagnostic work up. The Updates in Head and Neck Cytopathology Short Course ran during the 35th European Congress of Pathology held in Dublin, Ireland, in 2023 and brought together experts in cytopathology, pathology, and related fields to share their expertise and experience in the field of head and neck cytopathology and its future directions. Topics such as a one-stop clinic, the Milan System for Reporting Salivary Gland Cytopathology, next generation sequencing, and human papilloma virus detection in the head and neck area were covered during the short course. These topics are briefly summarized in the present review.


Asunto(s)
Neoplasias de las Glándulas Salivales , Glándulas Salivales , Humanos , Biopsia con Aguja Fina , Glándulas Salivales/patología , Cabeza/patología , Cuello/patología , Irlanda , Neoplasias de las Glándulas Salivales/patología , Estudios Retrospectivos
2.
Int J Mol Sci ; 19(6)2018 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-29890775

RESUMEN

Signal transducers and activator of transcription (STAT)-3 is activated in cancers, where it promotes growth, inflammation, angiogenesis, and inhibits apoptosis. Tissue microarrays were generated using tissues from 154 patients, with oesophageal adenocarcinoma (OAC) (n = 116) or squamous cell carcinoma (SCC) (n = 38) tumours. The tissues were stained for pSTAT3 and IL-6R using immunohistochemistry. The OE33 (OAC) and OE21 (SCC) cell lines were treated with the STAT3 inhibitor, STATTIC. The Univariate cox regression analysis revealed that a positive pSTAT3 in SCC was adversely associated with survival (Hazard ratio (HR) 6.382, 95% CI 1.266⁻32.184), while a protective effect was demonstrated with the higher pSTAT3 levels in OAC epithelium (HR 0.74, 95% CI 0.574⁻0.953). The IL-6R intensity levels were higher in the SCC tumours compared with the OAC tumours for the core and leading edge tumour tissue. The pSTAT3 levels correlated positively with the IL-6R levels in both the OAC and SCC. The treatment of OE21 and OE33 cells with the STAT3 inhibitor STATTIC in vitro resulted in decreased survival, proliferation, migration, and increased apoptosis. The pSTAT3 expression was associated with adverse survival in SCC, but not in the OAC patients. The inhibition of STAT3 in both of the tumour subtypes resulted in alterations in the survival, proliferation, migration, and apoptosis, suggesting a potential role for therapeutically targeting STAT3.


Asunto(s)
Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Factor de Transcripción STAT3/metabolismo , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Apoptosis , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Movimiento Celular , Proliferación Celular , Supervivencia Celular , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Humanos , Fosforilación , Modelos de Riesgos Proporcionales , Receptores de Interleucina-6/metabolismo , Análisis de Supervivencia , Análisis de Matrices Tisulares
3.
Am J Surg Pathol ; 47(6): 661-677, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37070739

RESUMEN

Salivary gland secretory carcinoma (SC), previously mammary analog SC, is a low-grade malignancy characterized by well-defined morphology and an immunohistochemical and genetic profile identical to SC of the breast. Translocation t(12;15)(p13;q25) resulting in the ETV6 :: NTRK3 gene fusion is a characteristic feature of SC along with S100 protein and mammaglobin immunopositivity. The spectrum of genetic alterations for SC continues to evolve. The aim of this retrospective study was to collect data of salivary gland SCs and to correlate their histologic, immunohistochemical, and molecular genetic data with clinical behavior and long-term follow-up. In this large retrospective study, we aimed to establish a histologic grading scheme and scoring system. A total of 215 cases of salivary gland SCs diagnosed between 1994 and 2021 were obtained from the tumor registries of the authors. Eighty cases were originally diagnosed as something other than SC, most frequently acinic cell carcinoma. Lymph node metastases were identified in 17.1% (20/117 cases with available data), with distant metastasis in 5.1% (6/117). Disease recurrence was seen in 15% (n=17/113 cases with available data). The molecular genetic profile showed ETV6 :: NTRK3 gene fusion in 95.4%, including 1 case with a dual fusion of ETV6 :: NTRK3 and MYB :: SMR3B . Less frequent fusion transcripts included ETV6 :: RET (n=12) and VIM :: RET (n=1). A 3-tiered grading scheme using 6 pathologic parameters (prevailing architecture, pleomorphism, tumor necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), and mitotic count and/or Ki-67 labeling index) was applied. Grade 1 histology was observed in 44.7% (n=96), grade 2 in 41.9% (n=90), and grade 3 in 13.5% (n=29) of cases. Compared with low-grade and intermediate-grade SC, high-grade tumors were associated with a solid architecture, more prominent hyalinization, infiltrative tumor borders, nuclear pleomorphism, presence of PNI and/or LVI, and Ki-67 proliferative index >30%. High-grade transformation, a subset of grade 2 or 3 tumors, seen in 8.8% (n=19), was defined as an abrupt transformation of conventional SC into high-grade morphology, sheet-like growth, and a tumor lacking distinctive features of SC. Both overall survival and disease-free survival (5 and 10 y) were negatively affected by tumor grade, stage, and TNM status (each P <0.0001). SC is a low-grade malignancy with predominantly solid-microcystic growth patterns, driven by a gene fusion, most commonly ETV6 :: NTRK3 . There is a low risk for local recurrence and a good overall long-term survival, with a low risk for distant metastasis but a higher risk for locoregional lymph node metastasis. The presence of tumor necrosis, hyalinization, PNI and/or LVI, and positive resection margins correlate with higher tumor grade, less favorable prognosis, and increased mortality. The statistical results allowed us to design a 3-tiered grading system for salivary SC.


Asunto(s)
Carcinoma Secretor Análogo al Mamario , Neoplasias de las Glándulas Salivales , Humanos , Estudios Retrospectivos , Antígeno Ki-67 , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Recurrencia Local de Neoplasia/genética , Neoplasias de las Glándulas Salivales/patología , Carcinoma Secretor Análogo al Mamario/genética , Glándulas Salivales/metabolismo , Glándulas Salivales/patología , Necrosis
4.
Cancers (Basel) ; 14(17)2022 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-36077856

RESUMEN

Human papillomavirus (HPV) infection has been identified as a significant etiological agent in the development of head and neck squamous cell carcinoma (HNSCC). HPV's involvement has alluded to better survival and prognosis in patients and suggests that different treatment strategies may be appropriate for them. Only some data on the epidemiology of HPV infection in the oropharyngeal, oral cavity, and laryngeal SCC exists in Europe. Thus, this study was carried out to investigate HPV's impact on HNSCC patient outcomes in the Irish population, one of the largest studies of its kind using consistent HPV testing techniques. A total of 861 primary oropharyngeal, oral cavity, and laryngeal SCC (OPSCC, OSCC, LSCC) cases diagnosed between 1994 and 2013, identified through the National Cancer Registry of Ireland (NCRI), were obtained from hospitals across Ireland and tested for HPV DNA using Multiplex PCR Luminex technology based in and sanctioned by the International Agency for Research on Cancer (IARC). Both overall and cancer-specific survival were significantly improved amongst all HPV-positive patients together, though HPV status was only a significant predictor of survival in the oropharynx. Amongst HPV-positive patients in the oropharynx, surgery alone was associated with prolonged survival, alluding to the potential for de-escalation of treatment in HPV-related OPSCC in particular. Cumulatively, these findings highlight the need for continued investigation into treatment pathways for HPV-related OPSCC, the relevance of introducing boys into national HPV vaccination programs, and the relevance of the nona-valent Gardasil-9 vaccine to HNSCC prevention.

5.
Front Mol Biosci ; 8: 677900, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34250016

RESUMEN

The Human Papilloma Virus (HPV) is an oncogenic virus which is associated with the development of head and neck squamous cell carcinoma (HNSCC), predominantly within the oropharynx. Approximately 25% of oropharyngeal squamous cell carcinoma (OPSCC) cases worldwide are attributable to HPV infection, with an estimated 65% in the United States. Transmission is via exposure during sexual contact, with distinctive anatomical features of the tonsils providing this organ with a predilection for infection by HPV. No premalignant lesion is identifiable on clinical examination, thus no comparative histological features to denote the stages of carcinogenesis for HPV driven HNSCC are identifiable. This is in contrast to HPV-driven cervical carcinoma, making screening a challenge for the head and neck region. However, HPV proffers a favorable prognosis in the head and neck region, with better overall survival rates in contrast to its HPV negative counterparts. This has resulted in extensive research into de-intensifying therapies aiming to minimize the morbidity induced by standard concurrent chemo-radiotherapy without compromising efficacy. Despite the favorable prognosis, cases of recurrence and/or metastasis of HPV positive HNSCC do occur, and are linked with poor outcomes. HPV 16 is the most frequent genotype identified in HNSCC, yet there is limited research to date studying the impact of other HPV genotype with respect to overall survival. A similar situation pertains to genetic aberrations associated in those with HPV positive HNSCC who recur, with only four published studies to date. Somatic mutations in TSC2, BRIP1, NBN, TACC3, NFE2l2, STK11, HRAS, PIK3R1, TP63, and FAT1 have been identified in recurrent HPV positive OPSCC. Finding alternative therapeutic strategies for this young cohort may depend on upfront identification of HPV genotypes and mutations which are linked with worse outcomes, thus ensuring appropriate stratification of treatment regimens.

6.
Head Neck Pathol ; 15(2): 461-468, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32918712

RESUMEN

We set out to record the frequency of recognised adverse pathologic features in early oral squamous cell carcinoma (OSCC) and correlate with neck disease, in particular in small and thin carcinomas, a group that might be assumed to behave less aggressively. We also examined the possibility of a biopsy site interfering with assessment of WPOI5 in small tumors. We reviewed all OSCCs ≤ 20 mm size and ≤ 10 mm depth reported at our institution over a 5-year period. Tumor maximum dimension, depth, perineural invasion (PNI), lymphovascular invasion (LVI), worst pattern of invasion (WPOI), and nodal status were recorded. Out of 95 cases, there were 44 (46.3%) small and 78 (82.1%) thin OSCCs. Depth and WPOI were significant factors in predicting nodal disease. There were 41 (43.2%) OSCC that were small and thin, of which 9.8% had PNI, none had LVI, and 61% had WPOI 4 or 5. Their rate of PNI and of nodal disease was similar to the other early OSCC. Assessment of WPOI5 at a biopsy site was only a problem in 2/38 cases. In early OSCC, depth and WPOI are important factors in predicting nodal disease. The very earliest OSCC (small and thin) have a similar rate of PNI and of nodal disease to other early OSCC, suggesting that while there may be a tendency to de-escalate treatment, these small tumours should be managed in the same way as for all early OSCC. In addition, the presence of scarring due to a biopsy in very small carcinomas rarely affects assessment of WPOI5.


Asunto(s)
Neoplasias de la Boca/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
7.
Int J Surg Pathol ; 17(3): 187-97, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19147513

RESUMEN

RET/PTC rearrangements are initiating events in the development of a significant proportion of papillary thyroid carcinomas. Activated RET/PTC mutations are thought to be restricted to thyroid disease, but this study proposes that these events may also occur in nonthyroid tumors. A total of 57 nonthyroid papillary tumors were examined for RET/PTC rearrangements using interphase fluorescence in situ hybridization, Taqman reverse transcriptase polymerase chain reaction, and immunohistochemistry. Taqman single nucleotide polymorphism detection was used to analyze for expression of mutated BRAF T1799A. In all, 20% (3/15) of primary peritoneal carcinoma had detectable RET/PTC1 rearrangements by all 3 methodologies. A further case of similar histotype had an alternate RET/ PTC rearrangement. No RET/PTC1 rearrangements were detected in the remaining tumor cohort. All 57 tumors were homozygous for wild-type BRAF. The results indicate that RET/PTC rearrangements occur in a small subset of nonthyroid papillary tumors. These rearrangements may not be directly implicated in tumor growth; rather representing "passenger" mutations reflecting RET instability in secondary tumor subclones.


Asunto(s)
Biomarcadores/análisis , Carcinoma Papilar/genética , Carcinoma/genética , Reordenamiento Génico , Neoplasias Peritoneales/genética , Proteínas Proto-Oncogénicas c-ret/genética , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas B-raf/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
8.
BMJ Case Rep ; 12(2)2019 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-30737321

RESUMEN

We report an extremely rare case of a hybrid tumour of the maxillary sinus. A 51-year-old man presented with a 6-week history of nasal congestion and epiphora. Radiological imaging demonstrated a maxillary sinus tumour, with extensive local invasion. Surgical excision included maxillectomy, left eye exenteration and free flap closure. Histology of the excised specimen showed a rare hybrid tumour containing adenoid cystic carcinoma, salivary duct carcinoma, epithelial-myoepithelial carcinoma and basal cell adenoma. Hybrid tumours are very rare tumour entities which are composed of at least two distinct tumour types. Each tumour entity conforms with a defined tumour type. The tumour entities of a hybrid tumour are not separated but have an identical origin within a definite topographical area. Diagnosis and appropriate management requires high index of suspicion, pathological endeavour to look for a more aggressive accompanying tumour and adequate oncological treatment according to the highest grade of tumour.


Asunto(s)
Carcinoma Adenoide Quístico/patología , Imagen por Resonancia Magnética , Neoplasias del Seno Maxilar/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Orbitales/patología , Senos Paranasales/patología , Neoplasias de las Glándulas Salivales/patología , Carcinoma Adenoide Quístico/diagnóstico por imagen , Carcinoma Adenoide Quístico/terapia , Hueso Etmoides/patología , Hueso Etmoides/cirugía , Humanos , Obstrucción del Conducto Lagrimal/diagnóstico por imagen , Masculino , Neoplasias del Seno Maxilar/diagnóstico por imagen , Neoplasias del Seno Maxilar/terapia , Persona de Mediana Edad , Obstrucción Nasal/diagnóstico por imagen , Neoplasias Primarias Múltiples/diagnóstico por imagen , Neoplasias Primarias Múltiples/terapia , Neoplasias Orbitales/diagnóstico por imagen , Neoplasias Orbitales/terapia , Procedimientos Quirúrgicos Ortognáticos , Radioterapia Adyuvante , Procedimientos de Cirugía Plástica/métodos , Neoplasias de las Glándulas Salivales/diagnóstico por imagen , Neoplasias de las Glándulas Salivales/terapia , Resultado del Tratamiento
9.
Hum Pathol ; 39(3): 452-8, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18261630

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) typically affects male smokers older than 55 years. Recently, an increase in the incidence of HNSCC in young adults has been recognized, many of them nonsmokers and females. Functional inactivation of p16 is known to be a common event in HNSCC, mainly by either deletion or methylation. A previous study by this group has shown that p16 deletions in HNSCC are significantly associated with age. The primary objective of this study was to evaluate additional molecular alterations of p16 in HNSCC, specifically in relation to age, site, and human papillomavirus (HPV) status. Patients ranging in age from 22 to 76 years with HNSCC were prospectively identified (n = 24). Methylation-specific polymerase chain reaction and immunohistochemistry were used to evaluate p16 gene inactivation and p16 protein expression, respectively. HPV 16 status was determined for each case. Overall, p16 inactivation was a frequent event detected in 46% of cases. Methylation of p16 was more often detected in females than males (P = .05). All cases showing p16 methylation were from the anterior tongue, and 75% of them were young patients. The results indicate that p16 methylation is a more common event in those younger than 40 years in contrast to p16 deletions, which are more common in those older than 40 years. Consequently, it appears that specific modes of inactivation of p16 in HNSCC are related to specific patient risk profiles. Interestingly, HPV 16 messenger RNA was detected exclusively in HNSCC from the base of tongue lesions and was only found in males. This differs from the patient profile of HNSCC in the young, which affects the anterior tongue and commonly females, thus, making it highly unlikely that this virus is a primary causative agent of HNSCC in these young adults.


Asunto(s)
Carcinoma de Células Escamosas/genética , Epigénesis Genética , Genes p16 , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Adulto , Factores de Edad , Anciano , Carcinoma de Células Escamosas/patología , ADN Viral/aislamiento & purificación , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/epidemiología , ARN Mensajero/análisis , Factores Sexuales , Fumar/efectos adversos
10.
Int J Surg Pathol ; 15(2): 116-20, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17478764

RESUMEN

Struma ovarii is an extremely rare tumor that occasionally undergoes malignant transformation. Because struma ovarii is composed of thyroid tissue, it is conceivable that the pathogenetic events involved in thyroid follicular transformation may take place also in struma ovarii. The authors describe a case of a classical variant of papillary thyroid carcinoma arising in a struma ovarii of a 22-year-old female. The tumor was heterozygous for BRAF T1799A mutation. No ret/ PTC-1 or ret/PTC-3 rearrangements were detected. This finding would suggest that malignant struma ovarii is similar histologically and genetically to primary papillary thyroid carcinoma.


Asunto(s)
Carcinoma Papilar Folicular/genética , Mutación , Neoplasias Ováricas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Estruma Ovárico/genética , Neoplasias de la Tiroides/genética , Adulto , Carcinoma Papilar Folicular/patología , Carcinoma Papilar Folicular/cirugía , ADN de Neoplasias/análisis , Femenino , Heterocigoto , Humanos , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Proteínas Proto-Oncogénicas B-raf/metabolismo , ARN Neoplásico/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estruma Ovárico/patología , Estruma Ovárico/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Resultado del Tratamiento
12.
Cancer Epidemiol Biomarkers Prev ; 26(5): 702-710, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28082347

RESUMEN

Background: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) represents a distinct subgroup of head and neck tumors. We analyze the expression of cytokeratin 7, a junctional biomarker with a SEQIKA fragment, which stabilizes HPV-16 E7 transcripts, in oropharyngeal SCCs.Methods: Archived tumor specimens and epidemiologic data were collected from patients with oropharyngeal SCCs over 10 years. Briefly, DNA was extracted from tissue blocks, and HPV testing was carried out using SPF10 HPV PCR and INNO-LiPA HPV Genotyping. Immunohistochemical staining for CK7 and p16ink4a was performed on the Ventana BenchMark Ultra Immunostainer. Analysis was by light microscopy using the H-score. CK7 expression was correlated with epidemiologic data, p16ink4a positivity, and HPV status using SPSS.Results: CK7 expression was observed specifically and uniformly in the tonsillar crypt epithelium of normal tonsils and tumor specimens. There were 226 cases of oropharyngeal SCCs, with 70 demonstrating both HPV and p16 positivity. Of 216 cases evaluated for CK7, 106 demonstrated some positivity, whereas H-score > 60 was seen in 55 of these. CK7 H-score > 60 was significantly associated with tonsillar subsite and HPV and p16 positivity.Conclusions: An association between CK7 and HPV has been demonstrated. CK7-expressing tonsillar crypt cells potentially represent an oropharyngeal subsite susceptible to HPV-related SCC.Impact: Along with the cervix and anorectum, specific oropharyngeal expression of CK7 in a site predisposed to HPV-related tumors may suggest a role for CK7 in the pathogenesis of this subgroup of tumors. Further research is warranted to characterize the association between CK7 and HPV-related head and neck SCC. Cancer Epidemiol Biomarkers Prev; 26(5); 702-10. ©2017 AACR.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/virología , Neoplasias de Cabeza y Cuello/virología , Queratina-7/biosíntesis , Neoplasias Orofaríngeas/virología , Adulto , Anciano , Femenino , Papillomavirus Humano 16 , Humanos , Queratina-7/análisis , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello
13.
Mol Cancer ; 5: 70, 2006 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-17156473

RESUMEN

BACKGROUND: microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nt in length that have been found to control cell growth, differentiation and apoptosis. miRNAs negatively regulate their target genes and recently have been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. ret/PTC 1 is an oncogene with constitutive kinase activity implicated in the development of papillary thyroid carcinoma (PTC). This rearrangement leads to aberrant MAPK activation that is implicated in PTC tumourigenesis. AIM: The aim of this study was to identify the effect that ret/PTC 1 has on transcription and post-transcriptional regulation in PTC by using DNA microarray and microRNA analysis. RESULTS: DNA microarray analysis revealed a group of genes differentially expressed between normal thyroid cell lines and those harbouring a ret/PTC 1 rearrangement.Furthermore, a unique miRNA expression signature differentiated between PTC cell lines with ret/PTC 1 and a normal thyroid cell line. 21 miRNAs showed significant overexpression and 14 miRNAs showed underexpression in these cell lines when compared to normal thyroid. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Papilar/metabolismo , MicroARNs/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteínas Tirosina Quinasas/genética , Procesamiento Postranscripcional del ARN , Neoplasias de la Tiroides/metabolismo , Transcripción Genética , Biomarcadores de Tumor/genética , Carcinoma Papilar/genética , Línea Celular Tumoral , Perfilación de la Expresión Génica , Reordenamiento Génico , Humanos , MicroARNs/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de la Tiroides/genética
14.
Artículo en Inglés | MEDLINE | ID: mdl-27544398

RESUMEN

Circumorificial plasmacytosis is a rare plasma cell proliferative disorder of the orificial mucous membranes. The etiology is unknown, and there are no reported effective treatments to date. We report three cases of idiopathic circumorificial plasmacytosis with varying clinical presentations and responses to treatment, including a first reported case of resolution with adalimumab therapy.


Asunto(s)
Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Mucosa Bucal/patología , Mucositis/diagnóstico , Mucositis/tratamiento farmacológico , Células Plasmáticas/patología , Anciano , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad
15.
Virchows Arch ; 445(4): 396-404, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15258756

RESUMEN

The susceptibility of thyroid epithelium to radiation-induced carcinogenesis is well recognised. In this context, thyroid carcinogenesis is associated with specific somatic ret/papillary thyroid carcinoma (PTC) rearrangements and morphologically with the papillary phenotype. Previous studies have demonstrated the possibility of inducing ret rearrangements in vitro using X-rays. The purpose of our study was to assess whether gamma (gamma) radiation using a Caesium 137 source can induce specific ret rearrangements in a human thyroid epithelial cell culture model. We further hypothesised that if radiation-induced thyroid carcinogenesis is associated with non-random rearrangement events, then DNA copy gain and loss induced by irradiation may also occur in a non-random manner. We irradiated SV40-immortalised human thyroid epithelial cells with incremental doses of gamma-radiation and, using TaqMan reverse-transcription polymerase chain reaction, looked for the presence of the common ret rearrangements. Cohorts showing evidence of ret/PTC chimeric transcripts were further analysed using microarray comparative genomic hybridisation (CGH) to detect copy gain and loss associated with radiation. Four Grays of gamma-radiation was sufficient to induce ret/PTC-3. In this model, transcripts of ret/PTC-1 were not detected, and we suggest that the type of radiation may influence the resulting rearrangement that occurs. Using array CGH, we have demonstrated a predominant pattern of subtelomeric deletions occurring in association with this radiation cohort and raise the possibility that chromosome 10 may be a hotspot for radiation-induced damage for as yet unknown reasons.


Asunto(s)
Carcinoma Papilar/genética , Neoplasias Inducidas por Radiación/genética , Proteínas Oncogénicas/genética , Glándula Tiroides/efectos de la radiación , Neoplasias de la Tiroides/genética , Línea Celular , Rayos gamma , Reordenamiento Génico , Humanos , Hibridación de Ácido Nucleico , Proteínas de Fusión Oncogénica , Proteínas Tirosina Quinasas , Glándula Tiroides/patología
16.
Arch Otolaryngol Head Neck Surg ; 130(4): 469-72, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15096433

RESUMEN

Linear IgA disease is a subepidermal blistering disorder of unknown cause. Along with dermatologic blistering, other manifestations include oral ulceration and desquamative gingivitis. We present a case of linear IgA disease that manifested simply as oropharyngeal ulceration and desquamative gingivitis, resulting in considerable delay in diagnosis and treatment. This article (1) highlights the difficulties of diagnosing linear IgA disease when the predominant presenting features are mucosal and (2) reviews the current literature regarding linear IgA disease.


Asunto(s)
Enfermedades Autoinmunes/patología , Gingivitis/patología , Inmunoglobulina A/metabolismo , Úlceras Bucales/patología , Enfermedades Autoinmunes/inmunología , Membrana Basal/inmunología , Membrana Basal/patología , Biopsia , Diagnóstico Diferencial , Técnica del Anticuerpo Fluorescente Indirecta , Encía/patología , Gingivitis/inmunología , Humanos , Masculino , Persona de Mediana Edad , Mucosa Bucal/inmunología , Mucosa Bucal/patología , Úlceras Bucales/inmunología
17.
World J Clin Cases ; 2(6): 172-93, 2014 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-24945004

RESUMEN

Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities.

18.
PLoS One ; 9(7): e102112, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25019640

RESUMEN

BACKGROUND: Induction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins. METHODS: Expression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry. RESULTS: We found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy. CONCLUSIONS: We identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated.


Asunto(s)
Biomarcadores/metabolismo , Reparación del ADN/fisiología , Proteínas de Unión al ADN/metabolismo , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Quimioterapia de Inducción/normas , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de Unión al ADN/genética , Perfilación de la Expresión Génica , Técnicas de Inactivación de Genes , Células HeLa , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Immunoblotting , Inmunohistoquímica , Quimioterapia de Inducción/métodos , Medicina de Precisión/métodos , Análisis de Supervivencia , Resultado del Tratamiento
19.
Urol Oncol ; 30(6): 900-5, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-21396847

RESUMEN

OBJECTIVE: To examine the role of RET in renal malignancy, in particular papillary renal cell carcinoma (RCC). MATERIALS AND METHODS: A cohort of 111 archival renal samples was used consisting of 94 renal cancers (66 papillary RCC, 18 conventional clear cell carcinoma, 10 chromophobe RCC), 4 benign oncocytomas, and 13 normal kidney tissues. RET protein expression was examined by immunohistochemistry and expression levels were correlated with clinicopathologic and patient survival data. RESULTS: Positive RET staining was seen in 34/66 (52%) papillary RCCs, 4/10 (40%) chromophobe carcinomas, 4/4 (100%) oncocytomas, and 11/13 (85%) normal kidney samples. All 18 cases of conventional clear cell carcinoma had negative RET staining. RET expression was associated with low Fuhrman nuclear grade. CONCLUSIONS: RET protein may be contributing in part to an adaptation of a papillary growth pattern in certain renal malignancies. Given the possible therapeutic benefit of small molecule inhibitors of RET activation, further work needs to be done to highlight the functional relevance of RET protein expression in papillary RCC.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/metabolismo , Proteínas Proto-Oncogénicas c-ret/biosíntesis , Carcinoma de Células Renales/patología , Femenino , Humanos , Inmunohistoquímica , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas c-ret/análisis
20.
PLoS One ; 4(6): e5877, 2009 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-19517019

RESUMEN

There is increasing evidence that p63, and specifically DeltaNp63, plays a central role in both development and tumorigenesis by promoting epithelial cell survival. However, few studies have addressed the molecular mechanisms through which such important function is exerted. Fatty acid synthase (FASN), a key enzyme that synthesizes long-chain fatty acids and is involved in both embryogenesis and cancer, has been recently proposed as a direct target of p53 family members, including p63 and p73. Here we show that knockdown of either total or DeltaN-specific p63 isoforms in squamous cell carcinoma (SCC9) or immortalized prostate epithelial (iPrEC) cells caused a decrease in cell viability by inducing apoptosis without affecting the cell cycle. p63 silencing significantly reduced both the expression and the activity of FASN. Importantly, stable overexpression of either FASN or myristoylated AKT (myr-AKT) was able to partially rescue cells from cell death induced by p63 silencing. FASN induced AKT phosphorylation and a significant reduction in cell viability was observed when FASN-overexpressing SCC9 cells were treated with an AKT inhibitor after p63 knockdown, indicating that AKT plays a major role in FASN-mediated survival. Activated AKT did not cause any alteration in the FASN protein levels but induced its activity, suggesting that the rescue from apoptosis documented in the p63-silenced cells expressing myr-AKT cells may be partially mediated by FASN. Finally, we demonstrated that p63 and FASN expression are positively associated in clinical squamous cell carcinoma samples as well as in the developing prostate. Taken together, our findings demonstrate that FASN is a functionally relevant target of p63 and is required for mediating its pro-survival effects.


Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Ácido Graso Sintasas/metabolismo , Proteínas de la Membrana/fisiología , Apoptosis , Ciclo Celular , Línea Celular Tumoral , Supervivencia Celular , Proteínas de Unión al ADN/metabolismo , Células Epiteliales , Silenciador del Gen , Humanos , Proteínas de la Membrana/metabolismo , Modelos Biológicos , Ácidos Mirísticos/metabolismo , Proteínas Nucleares/metabolismo , Fosforilación , Isoformas de Proteínas , Proteína Tumoral p73 , Proteínas Supresoras de Tumor/metabolismo
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