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1.
Cancers (Basel) ; 16(1)2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38201653

RESUMEN

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers. Archived tumor tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010-2020. The HPV-positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016-2020 vs. 40.4% (19/47) in 2010-2015, p = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, p = 0.006), but no significant difference was observed between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers.

2.
Virchows Arch ; 484(1): 119-125, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38063896

RESUMEN

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a novel entity characterized by its unique translocation and malignant clinical course. In this study, AFF immunohistochemistry (IHC) was performed in recurrent sinonasal papillomas for reviewing the prevalence of undiagnosed DEK::AFF2 carcinomas and to investigate the performance of AFF IHC in diagnosis of DEK::AFF2 carcinomas. Recurrent sinonasal papillomas after surgical excision in a two-decade period were retrieved. Histologic slides were reviewed for features of DEK::AFF2 carcinoma. AFF IHC was performed, and cases with any (> 1%) nuclear positivity were validated by DEK break apart fluorescence in situ hybridization. Totally 43 cases were included, comprising 28 inverted, 6 exophytic, one oncocytic, and 8 non-specified sinonasal papillomas. Five (11.6%) cases exhibited positivity to AFF IHC. Three cases exhibited patchy weak to moderate staining intensity predominantly in a granular cytoplasmic pattern. Two cases exhibited strong and diffuse (> 90%) nuclear staining. Cases showing weak staining were negative for DEK rearrangement, while those with strong staining were positive. Both cases of DEK::AFF2 carcinoma showed aggressive behavior with extensive local invasion and nodal metastasis. Background stromal plasma cells, when present, consistently showed strong and diffuse staining. AFF IHC was further performed in plasmacytoma samples as control and showed strong and diffuse immunoreactivity. A significant minority of recurrent sinonasal papillomas represent DEK::AFF2 carcinomas. Granular, cytoplasmic, or incomplete AFF staining should be considered as negative. In view of the rarity of DEK::AFF2 carcinomas, plasma cells and plasma cell neoplasms are potential for internal and surrogate external controls.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Papiloma , Humanos , Estudios Retrospectivos , Prevalencia , Hibridación Fluorescente in Situ , Papiloma/patología , Carcinoma de Células Escamosas/patología , Proteínas Nucleares
3.
Head Neck Pathol ; 17(4): 1058-1063, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37938508

RESUMEN

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a recently characterized sinonasal malignancy defined by its unique translocation. DEK::AFF2 carcinomas may be deceptively monotonous and lack keratinization, resembling transitional epithelium. The lack of traditional cytological atypia presents diagnostic challenges. Our case describes the first report of fine-needle aspiration cytology of a lymph node involved by DEK::AFF2 carcinoma in a patient with previously resected sinonasal inverted papilloma with carcinomatous transformation six years prior to presentation. This aspirate consisted of a lymphoid-rich background admixed with a moderate amount of epithelial cells arranged in cohesive structures of variable size, including large sheets. The tumor cells resembled those of the corresponding biopsy, featuring mildly hyperchromatic nuclei with fine to vesicular chromatin. Lesional cells lacked keratinization, mitoses, or hyperchromasia. Our finding suggests that in nodal aspirates of patients with a history of sinonasal-type papillomas, especially those with prior malignant transformation or atypia, there should be consideration for the possibility of DEK::AFF2-related primary. When in doubt, DEK FISH of AFF2 immunohistochemistry should be performed for confirmation.


Asunto(s)
Carcinoma Papilar , Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Papiloma , Humanos , Biopsia con Aguja Fina , Carcinoma Papilar/patología , Neoplasias de Cabeza y Cuello/patología , Citodiagnóstico , Carcinoma de Células Escamosas/patología , Papiloma/patología , Proteínas Nucleares
4.
Head Neck Pathol ; 16(3): 934-941, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35257325

RESUMEN

SMARCB1 (INI1)-deficient carcinoma of the sinonasal tract is a rare and distinct entity characterized by the loss of INI1 immunostain expression. These tumors are morphologically diverse, with isolated cases of yolk sac differentiation reported. We report the first case of SMARCB1-deficient sinonasal carcinoma that demonstrated co-loss of SMARCA4 immunostain, and reduced SMARCA2 and ARID1A staining, with the entire tumor showing histological and immunohistochemical evidence of yolk sac differentiation. The clinical, histological, immunohistochemical and molecular features were discussed and compared against SMARCB1-deficient sinonasal carcinomas with yolk sac differentiation and SMARCA4-deficeint sinonasal carcinomas reported in the literature. With a highly aggressive clinical course leading to mortality two months after presentation, the behavior of this tumor appears to be more comparable to that of SMARCA4-deficient sinonasal carcinomas. A comprehensive immunopanel including SMARCB1, SMARCA4, SMARCA2 and ARID1A may be advisable for assessment and prognostication of SWI/SNF-deficient tumors.


Asunto(s)
Carcinoma , Neoplasias de los Senos Paranasales , Biomarcadores de Tumor , ADN Helicasas , Humanos , Inmunohistoquímica , Proteínas Nucleares , Proteína SMARCB1 , Factores de Transcripción , Saco Vitelino
5.
Diagn Cytopathol ; 50(2): 64-74, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34927804

RESUMEN

OBJECTIVE: Squamous metaplasia is not uncommonly observed in salivary gland neoplasms, including pleomorphic adenomas (PAs). It poses as a diagnostic pitfall with cytomorphologic features overlapping with low-grade epithelial malignances and carcinoma ex-PA. We report series of aspirates of PAs with squamous metaplasia and review the literature for the clinicopathological and cytologic features of this diagnostically challenging entity. METHODS: Three cases including index aspiration cytology, post-aspiration specimen cytology, cell block immunohistochemistry (IHC), histologic correlation, and clinical data were reviewed. Literature search was performed for cases of PAs with squamous metaplasia, yielding 22 case reports including 11 with aspiration cytology performed. RESULTS: Metaplastic squamous components were seen in all index aspirations, but foreign body reaction and cystic changes were observed only after aspiration or in irritated lesions. PLAG1 IHC demonstrated reliable immunoreactivity in cell block preparations. Summarizing cases in this series and in the literature, cytologic features reported were variable and no consistent diagnostic feature was identified. Most reported cases were initially diagnosed as suspicious or malignant, but all ran a benign clinical course. Significant morbidity was reported only in one case due extensive surgery based on a malignant diagnosis. CONCLUSIONS: Squamous metaplasia in PAs is not associated with adverse outcomes, but may induce reactive changes upon aspiration/irritation, resulting in worrisome cytologic features. PLAG1 IHC is a useful adjunct when characteristic cytologic features for PAs are absent or obscured. Prudent use of the diagnostic category salivary gland neoplasm of uncertain malignant potential (SUMP) in the Milan system can avoid overtreatment.


Asunto(s)
Adenoma Pleomórfico/diagnóstico , Adenoma Pleomórfico/patología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/patología , Adenoma Pleomórfico/diagnóstico por imagen , Adulto , Anciano , Biopsia con Aguja Fina , Carcinoma de Células Escamosas/diagnóstico por imagen , Proteínas de Unión al ADN/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Metaplasia , Persona de Mediana Edad , Neoplasias de las Glándulas Salivales/diagnóstico por imagen
6.
Cancers (Basel) ; 13(23)2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34885177

RESUMEN

Early diagnosis and treatment do not prevent the high morbidity and poor prognosis of oral tongue squamous cell carcinoma (TSCC). Earlier studies have shown that ARG1 signaling is deregulated in TSCC. Here, we investigated the complexity of ARG1 metabolism in this cancer subsite to appreciate the therapeutic potential of this potential biological vulnerability. Various functional studies show that ARG1 overexpression in oral cancer cells inhibits cell proliferation and invasion compared with controls. Further, RNA-sequencing revealed numerous differentially expressed genes (DEGs) and associated networks were dysregulated by ARG1 overexpression, including hypoxia-inducible factor (HIFα) signaling, the natural killer cell signaling pathway and interferon signaling. Our work provides a foundation for understanding the mechanism of action of disrupted arginine metabolism in oral tongue squamous cell carcinoma. This may impact the community for developing further therapeutic approaches.

7.
Cancers (Basel) ; 12(11)2020 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-33218162

RESUMEN

The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of Fusobacterium and Peptostreptococcus in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, Fusobacterium nucleatum abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of F. nucleatum was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes LXN and SMARCA2, for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host-microbe interactions between F. nucleatum enrichment and clinical outcomes or host gene methylation imply a potential role of F. nucleatum as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.

8.
Pathology ; 51(6): 600-604, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31445809

RESUMEN

Oncocytic metaplastic lesions of the nasopharynx are rare benign entities which are divided into melanotic and non-melanotic forms. Less than 40 non-melanotic and 30 melanotic cases have been reported in the literature. We present the largest known case series to date of melanotic oncocytic metaplasia and more than 20 cases of non-melanotic oncocytic metaplasia. Clinical, endoscopic, histological and immunohistochemical features were reviewed. Most cases presented in males starting from their late adulthood. Compared to its non-melanotic counterpart, all cases of melanotic oncocytic metaplasia had a smoking history (p=0.041). All cases of melanotic oncocytic metaplasia were negative to melanocytic markers (S100, HMB-45, Melan-A and MiTF). Although no disease-related mortality was recorded, concurrent melanoma and nasopharyngeal carcinoma were seen in two cases.


Asunto(s)
Melanocitos/patología , Nasofaringe/patología , Células Oxífilas/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Metaplasia/patología , Persona de Mediana Edad
9.
Mol Ther ; 26(9): 2295-2303, 2018 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-30005868

RESUMEN

Thyroid cancer is rapidly increasing in incidence worldwide. Although most thyroid cancer can be cured with surgery, radioactive iodine, and/or chemotherapy, thyroid cancers still recur and may become chemoresistant. Autophagy is a complex self-degradative process that plays a dual role in cancer development and progression. In this study, we found that miR-125b was downregulated in tissue samples of thyroid cancer as well as in thyroid cancer cell lines, and the expression of Foxp3 was upregulated. Further, we demonstrated that miR-125b could directly act on Foxp3 by binding to its 3' UTR and inhibit the expression of Foxp3. A negative relationship between miR-125b and Foxp3 was thus revealed. Overexpression of miR-125b markedly sensitized thyroid cancer cells to cisplatin treatment by inducing autophagy through an Atg7 pathway in vitro and in vivo. Taken together, our findings demonstrate a novel mechanism by which miR-125b has the potential to negatively regulate Foxp3 to promote autophagy and enhance the efficacy of cisplatin in thyroid cancer. miR-125 may be of therapeutic significance in thyroid cancer.


Asunto(s)
Autofagia/efectos de los fármacos , Factores de Transcripción Forkhead/metabolismo , MicroARNs/metabolismo , Neoplasias de la Tiroides/metabolismo , Regiones no Traducidas 3'/efectos de los fármacos , Regiones no Traducidas 3'/genética , Autofagia/genética , Línea Celular Tumoral , Cisplatino/farmacología , Factores de Transcripción Forkhead/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Técnicas In Vitro , MicroARNs/genética , Neoplasias de la Tiroides/genética
10.
F1000Res ; 7: 499, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29862022

RESUMEN

Soft tissue sarcoma of the tongue represents a very rare head and neck cancer with connective tissue features, and the genetics underlying this rare cancer are largely unknown. There are less than 20 cases reported in the literature thus far. Here, we reported the first whole-exome characterization (>×200 depth) of an undifferentiated sarcoma of the tongue in a 31-year-old male. Even with a very good sequencing depth, only 19 nonsynonymous mutations were found, indicating a relatively low mutation rate of this rare cancer (lower than that of human papillomavirus (HPV)-positive head and neck cancer). Yet, among the few genes that are somatically mutated in this HPV-negative undifferentiated tongue sarcoma, a noticeable deleterious frameshift mutation (with a very high allele frequency of >93%) of a gene for DNA replication and repair, namely POLDIP2 (DNA polymerase delta interacting protein 2), and two recurrent mutations of the adipogenesis and adipocyte differentiation gene RETSAT (retinol saturase), were identified. Thus, somatic events likely affecting adipogenesis and differentiation, as well as potential stem mutations to POLDIP2, may be implicated in the formation of this rare cancer. This identified somatic whole-exome sequencing profile appears to be distinct from that of other reported adult sarcomas from The Cancer Genome Atlas, suggesting a potential unique genetic profile for this rare sarcoma of the tongue. Interestingly, this low somatic mutation rate is unexpectedly found to be accompanied by multiple tumor protein p53 and NOTCH1 germline mutations of the patient's blood DNA. This may explain the very early age of onset of head and neck cancer, with likely hereditary predisposition. Our findings are, to our knowledge, the first to reveal a unique genetic profile of this very rare undifferentiated sarcoma of the tongue.

11.
J Med Virol ; 90(6): 1150-1159, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29446476

RESUMEN

To delineate the role of human papillomavirus (HPV) in laryngeal cancer in Southern Chinese, a retrospective cross-sectional study was conducted in a major otorhinolaryngology referral center in Hong Kong. Eighty-five Chinese patients with histology-confirmed laryngeal squamous cell carcinoma (LSCC) diagnosed between 2005 and 2010 were examined for the status of HPV by PCR, and the expression of p16 and p53 by immunohistochemistry. The HPV, p16 and p53 findings were correlated with clinicopathological features, recurrence and 5-year survival. HPV DNA was detected in one patient (1.2%, 95%CI: 0.2-6.4%) who had glottic cancer and harbored HPV-6. Overexpression of p16 and p53 were detected in 11 (12.9%) and 47 (55.3%) cases, respectively. Recurrence occurred in 22.4% of patients at a median of 13 months. The 5-year overall survival and disease-specific survival were 55.7% and 72.4%, respectively. Overexpression of p16 or p53 was not associated with clinicopathological features, recurrence or overall survival. HPV plays a limited role in laryngeal cancer in Hong Kong Southern Chinese. In contrast to oropharyngeal cancer, p16 cannot be used as a surrogate marker for oncogenic involvement of HPV and cannot predict survival in laryngeal cancer.


Asunto(s)
Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/virología , Neoplasias Laríngeas/epidemiología , Neoplasias Laríngeas/virología , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Estudios Transversales , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , ADN Viral/análisis , ADN Viral/genética , Femenino , Hong Kong/epidemiología , Humanos , Inmunohistoquímica , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/análisis
12.
J Cell Biochem ; 117(11): 2473-81, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-26970173

RESUMEN

Oxidative stress-induced DNA damage is a known causing factor for many types of tumors, but information on the role of oxidants and antioxidants in thyroid tumors is limited. The aim of this study was to determine antioxidant levels in thyroid tumors. In this study, tumor and its matched non-tumor thyroid tissue samples were obtained from 53 patients with thyroid tumors. The levels of manganese superoxide dismutase (MnSOD), thioredoxin reductase 2 (TXNRD2), glutathione (GSH), glutathione peroxidase (Gpx), catalase (CAT), and 27 kd heat-shock protein (hsp27) were determined in both thyroid tissue samples and cultured thyroid cells by immunohistochemical staining and western blot. Hydrogen peroxide (H2 O2 ) was used to generate oxidant stress in the cell culture experiments. We found that the levels of MnSOD, TXNRD2, GSH, Gpx, and Hsp27 were increased in both malignant and benign tumors, while the level of CAT was decreased. To verify the results of the tissue study, we treated cultured thyroid cells with H2 O2 and found the same pattern of antioxidant changes. Hsp27 was also increased after H2 O2 treatment. The expression of hsp27 was upregulated by 8.24-, 6.96-, and 3.09-fold in thyroid cancer, follicular adenoma, multinodular goiter, respectively. Collectively, our study demonstrated that the levels of hsp27 together with MnSOD, TXNRD2, GSH, and Gpx were significantly upregulated by H2 O2 in thyroid tumors. The increase of these antioxidants is observed in both malignant and benign tumors, particularly in the former. The upregulation of antioxidants is likely a protective mechanism of tumor cells to maintain their survival and growth. J. Cell. Biochem. 117: 2473-2481, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Adenocarcinoma Folicular/metabolismo , Antioxidantes/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma Papilar/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Glándula Tiroides/metabolismo , Neoplasias de la Tiroides/metabolismo , Adenocarcinoma Folicular/patología , Carcinoma Papilar/patología , Células Cultivadas , Regulación Neoplásica de la Expresión Génica , Proteínas de Choque Térmico , Humanos , Técnicas para Inmunoenzimas , Chaperonas Moleculares , Estrés Oxidativo , Neoplasias de la Tiroides/patología
13.
Cancer Epidemiol Biomarkers Prev ; 25(1): 165-73, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26604268

RESUMEN

BACKGROUND: Although the global incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing, there is little information on southern Chinese population available. METHODS: We analyzed 207 patients which constituted 63.5% of all newly diagnosed OPSCC in Hong Kong during a 5-year period from 2005 to 2009. RESULTS: We used E6/7 mRNA as a marker of oncogenic involvement and found 20.8% (43/207) of OPSCC and 29.0% (36/124) of tonsillar SCC was associated with HPV. HPV-16 was identified in all cases except one (HPV-18). Patients with HPV-associated OPSCCs were significantly younger than HPV-negative patients (mean age: 59.8 vs. 63.9 years, P = 0.05). Multivariate analysis showed that HPV-associated OPSCC was more likely to occur in nonsmokers (39.5% vs. 15.1%, OR: 2.89, P = 0.05), nondrinkers (52.5% vs. 25.6%, OR: 2.72, P = 0.04), originate from the palatine tonsils (83.7% vs. 53.7%, OR: 3.88, P = 0.01), present with an early primary tumor (T1/2; 79.1% vs. 47.6%, OR: 3.81, P = 0.004), and exhibit basaloid differentiation (33.3% vs. 7.3%, OR: 19.74, P = 0.006). HPV positivity was an independent predictor for better prognosis for both 5-year overall and 5-year disease-specific survivals (DSS; 63.0% vs. 29.7%, HR: 0.33, P < 0.001, and 87.8% vs. 42.6%, HR: 0.16, P < 0.001, respectively). CONCLUSION: The estimated age-standardized incidence of OPSCC in Hong Kong during the period 2005-2009 was 0.12/100,000/year. IMPACT: This study has provided the most comprehensive clinical and pathologic information to date about this newly recognized disease in southern Chinese. In view of the global trend, we should anticipate and prepare for an increase in HPV-related OPSCC in southern China.


Asunto(s)
Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Neoplasias Orofaríngeas/epidemiología , Neoplasias Orofaríngeas/patología , Infecciones por Papillomavirus/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/virología , China/epidemiología , ADN Viral/genética , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Orofaríngeas/virología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Prevalencia , Pronóstico
14.
J Med Virol ; 88(5): 877-87, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26467027

RESUMEN

HPV plays a role in the development of a portion of head and neck squamous cell carcinoma (HNSCC), but only limited information on its role in southern Chinese population is available. A multicenter case-control study was conducted. HPV type, viral integration, E6/7 mRNA expression status, and TP53 mutation were determined. A total of 228 HNSCC were recruited including 137 (60.1%) oral SCC, 34 (14.9%) oropharyngeal SCC, 31 (13.6%) laryngeal SCC, 21 (9.2%) hypopharyngeal SCC, and 5 (2.2%) lip and paranasal sinus SCC. High-risk HPV infection was found in 7.5% (17/228) of HNSCC, but only a small proportion of samples had evidence of viral integration (5.3%, 12/228) or E6/7 mRNA expression (4.4%, 10/228). HPV infection with oncogenic phenotype (integration and E6/7 mRNA expression) was significantly more common in oropharyngeal SCC than controls (9/34, 26.5% vs. 0/42, 0.0%, P < 0.001). Smoking showed a significant association with HNSCC, oropharyngeal SCC, and laryngeal SCC. TP53 mutation was associated with HNSCC (P < 0.001). Older age, TP53 mutation, and HPV16 infection with oncogenic phenotypes were independently associated factors for HNSCC with odds ratios of 1.03 (1.02-1.05), 3.38 (1.71-6.66), and 9.19 (1.13-74.68), respectively. High-risk HPV infection of head and neck mucosa is not uncommon in the Hong Kong population. This study found that 26-30% of oropharyngeal carcinoma was associated with HPV infection, mostly HPV16, and that smoking which predisposes to TP53 mutations was another important risk factor.


Asunto(s)
Carcinoma de Células Escamosas/virología , Neoplasias de Cabeza y Cuello/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Carcinoma de Células Escamosas/epidemiología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Perfilación de la Expresión Génica , Neoplasias de Cabeza y Cuello/epidemiología , Hong Kong/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas Virales/biosíntesis , Proteínas Oncogénicas Virales/genética , Papillomaviridae/clasificación , Infecciones por Papillomavirus/epidemiología , Factores de Riesgo , Fumar , Proteína p53 Supresora de Tumor/genética , Integración Viral , Adulto Joven
15.
J Clin Endocrinol Metab ; 100(4): E561-71, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25594859

RESUMEN

CONTEXT: The incidence of papillary thyroid cancer (PTC) shows a predominance in females, with a male:female ratio of 1:3, and none of the known risk factors are associated with gender difference. Increasing evidence indicates a role of estrogen in thyroid tumorigenesis, but the mechanism involved remains largely unknown. OBJECTIVE: This study aimed to assess the contribution of autophagy to estrogen receptor α (ERα)-mediated growth of PTC. DESIGN: The expression of ERα in thyroid tissue of patients with PTC tissues was analyzed. Cell viability, proliferation, and apoptosis were evaluated after chemical and genetic inhibition of autophagy. Autophagy in PTC cell lines BCPAP and BCPAP-ERα was assessed. RESULTS: ERα expression was increased in PTC tissues compared with the adjacent nontumor tissues. Estrogen induced autophagy in an ERα-dependent manner. Autophagy induced by estrogen/ERα is associated with generation of reactive oxygen species, activation of ERK1/2, and the survival/growth of PTC cells. Chemical and genetic inhibition of autophagy dramatically decreased tumor cell survival and promoted apoptosis, confirming the positive role of autophagy in the growth of PTC. CONCLUSIONS: ERα contributes to the growth of PTC by enhancing an important prosurvival catabolic process, autophagy, in PTC cells. The inhibition of autophagy promotes apoptosis, implicating a novel strategy for the treatment of ERα-positive PTC.


Asunto(s)
Autofagia/genética , Carcinoma , Receptor alfa de Estrógeno/fisiología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Tiroides , Adolescente , Adulto , Anciano , Autofagia/efectos de los fármacos , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patología , Carcinoma Papilar , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Estradiol/farmacología , Femenino , Humanos , Células MCF-7 , Masculino , Persona de Mediana Edad , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Células Tumorales Cultivadas , Regulación hacia Arriba , Adulto Joven
16.
Mol Cell Endocrinol ; 399: 228-34, 2015 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-25312920

RESUMEN

Foxp3+ regulatory T cells (Tregs) in lymphocytes facilitate the thyroid tumor growth and invasion. Very limited information is available on Foxp3 expression in thyroid cancer cells and its function is totally unknown. This study demonstrated that Foxp3 expression was increased in thyroid cancer cells. Inhibition of Foxp3 decreased cell proliferation and migration, but increased apoptosis, suggesting a positive role of Foxp3 in cancer growth. Interestingly, Foxp3 inhibition enhanced PPARγ expression and activity. In addition, Foxp3 inhibition downregulated NF-κB subunit p65 and cyclin D1 but upregulated caspase-3 levels. These molecular changes are in line with Foxp3 shRNA-mediated alteration of cell functions. Collectively, our study demonstrates that thyroid cancer cells express a high level of functional Foxp3 and that the inhibition of the Foxp3 suppresses the proliferation and migration but promotes apoptosis, suggesting that targeting Foxp3 in thyroid cancer cells may offer a novel therapeutic option for thyroid cancer.


Asunto(s)
Apoptosis , Factores de Transcripción Forkhead/biosíntesis , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/metabolismo , Neoplasias de la Tiroides/metabolismo , Movimiento Celular , Proliferación Celular , Ciclina D1/metabolismo , Humanos , Células Jurkat , PPAR gamma/metabolismo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Factor de Transcripción ReIA/metabolismo
17.
Cancer ; 120(1): 142-53, 2014 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-24114184

RESUMEN

BACKGROUND: Estrogen receptor (ER) and peroxisome proliferator-activated receptor gamma (PPARγ) are associated with thyroid tumorigenesis and treatment. However, the interaction between them has not been studied. METHODS: The impact of ER over-expression or down-expression by DNA/small interfering RNA (siRNA) transfection, ERα agonists, and the ERß agonist diarylpropiolnitrile (DPN) on PPARγ expression/activity was examined in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) cells. The effects of PPARγ modulation by rosiglitazone (RTZ), a PPARγ ligand, and of PPARγ siRNA on ER expression were determined. Cellular functions reflected by cell proliferation and migration were assayed. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick-end labeling, and apoptotic-related proteins were evaluated by Western blot analysis. RESULTS: PPARγ protein and activity were reduced by the over-expression of either ERα or ERß, whereas repression of ERα or ERß increased PPARγ expression. The administration of RTZ counteracted the effects of ER and also reduced their expression, particularly in PTC cells. Moreover, knockdown of PPARγ increased ER expression and activity. Functionally, ERα activation offset the inhibitory effect of PPARγ on cellular functions, but ERß activation aggregated it and induced apoptosis, particularly in PTC cells. Finally, the interaction between ERß and PPARγ enhanced the expression of proapoptotic molecules, such as caspase-3 and apoptosis-inducing factor. CONCLUSIONS: This study provides evidence supporting a cross-talk between ER and PPARγ. The reciprocal interaction between PPARγ and ERß significantly inhibits the proliferation and migration of thyroid cancer cells, providing a new therapeutic strategy against thyroid cancer.


Asunto(s)
Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , PPAR gamma/metabolismo , Neoplasias de la Tiroides/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Procesos de Crecimiento Celular/fisiología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Receptor alfa de Estrógeno/biosíntesis , Receptor alfa de Estrógeno/deficiencia , Receptor beta de Estrógeno/biosíntesis , Receptor beta de Estrógeno/deficiencia , Técnicas de Silenciamiento del Gen , Humanos , PPAR gamma/biosíntesis , Receptor Cross-Talk , Rosiglitazona , Transducción de Señal , Tiazolidinedionas/farmacología , Neoplasias de la Tiroides/patología , Transfección
19.
Otolaryngol Head Neck Surg ; 143(6): 795-800, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21109080

RESUMEN

OBJECTIVE: To evaluate the relationship of functional magnetic resonance imaging (MRI) parameters, including choline/creatine ratio (Cho/Cr) and apparent diffusion coefficient (ADC) with protein expression of 10 common tumor and prognostic markers in head and neck squamous cell carcinoma. STUDY DESIGN: Cross-sectional study. SETTING: University hospital. SUBJECTS AND METHODS: The Cho/Cr and ADC obtained from 74 patients with head and neck squamous cell carcinoma were correlated with the expression level of the 10 protein markers as determined by immunohistochemistry. RESULTS: Cho/Cr showed significant positive correlations with cyclooxygenase 2 in primary tumors (r = 0.714), and epidermal growth factor receptor in metastatic cervical lymph nodes (r = 0.522). ADC showed significant (r = -0.591) negative correlation with human epidermal growth factor receptor 2 in metastatic cervical lymph nodes. CONCLUSION: There are relationships between protein and functional MRI markers. Future research in this direction may improve our understanding of the cancer micro-environment.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/metabolismo , Colina/análisis , Creatina/análisis , Estudios Transversales , Ciclooxigenasa 2/biosíntesis , Imagen de Difusión por Resonancia Magnética , Receptores ErbB/biosíntesis , Humanos , Inmunohistoquímica , Ganglios Linfáticos/química , Ganglios Linfáticos/fisiopatología , Imagen por Resonancia Magnética , Cuello , Pronóstico
20.
Hong Kong Med J ; 16(4): 307-9, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20683076

RESUMEN

Normal nasopharyngeal mucosa contains varying amounts of lymphoid tissue, which in adults may be minimal or absent. Nasopharyngeal mucosa with minimal lymphoid tissue has a regular follicular pattern on narrow-band imaging; pale follicles have thin, dark borders and the ratio of the pale follicle to the dark border (pale-to-dark ratio) is roughly 90%. In some patients undergoing routine nasopharyngeal endoscopy, the pale-to-dark ratio is reversed on narrow-band imaging, with dark centres surrounded by pale borders and a pale-to-dark ratio of roughly 50%. These dark follicles may represent abnormal capillary loops, as they have the same appearance as microvascular changes seen on narrow-band imaging of the oesophageal mucosa which indicate dysplasia or malignancy. While this observed change in the follicular pattern may be an early event in the evolution of nasopharyngeal carcinoma, the significance of this finding remains to be confirmed by a larger-scale study.


Asunto(s)
Endoscopía/métodos , Esófago/patología , Neoplasias Nasofaríngeas/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Neoplasias Nasofaríngeas/patología , Nasofaringe/patología
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