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1.
Clin Otolaryngol ; 44(6): 1087-1095, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31574203

RESUMEN

OBJECTIVES: Perineural invasion (PNI) is a poor prognostic pathologic feature of oral squamous cell carcinoma (OSCC). The mechanisms of PNI remain poorly understood, and nerve-tumour interactions have been implicated for its pathogenesis. DESIGN AND SETTING: Systematic investigation of nerve-tumour interactions was performed using fresh human peripheral nerve. In vitro and in vivo models were used to determine the ability of human peripheral nerves to enhance OSCC migration/invasion. Retrospective cohort study was also carried out in one medical centre from 2001 to 2009. PARTICIPANTS: 314 T1-2 OSCC patients. MAIN OUTCOME MEASURES: In the transwell migration/invasion assay, the cells in five representative fields were counted. In the nerve implantation model, tumour size was estimated. PNI quantification by PNI focus number was carried out in the OSCC patients to correlate with cervical lymph node metastasis and oncologic outcomes. RESULTS: The transwell migration/invasion assay demonstrated that human peripheral nerves, compared with subcutaneous soft tissue, significantly enhanced the migration/invasion abilities of OSCC. Moreover, the enhanced migration was dose-dependent with increased length or number of peripheral nerve segments. The nerve implantation model showed that human peripheral nerve also enhanced OSCC growth in vivo. Finally, increased PNI focus number was found dose-dependently associated with increased cervical lymph node metastasis and decreased 5-year disease-specific survival rates. CONCLUSIONS: These results clearly indicated the presence of nerve-tumour interaction that involved paracrine influences leading to aggressiveness of OSCC. Further investigations are required to explore key cell types and molecules involved in nerve-tumour interactions for future therapeutic targeting of PNI in OSCC.


Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Invasividad Neoplásica/patología , Nervios Periféricos/patología , Animales , Línea Celular Tumoral , Movimiento Celular , Humanos , Metástasis Linfática/patología , Ratones Desnudos , Pronóstico , Estudios Retrospectivos
2.
Histopathology ; 71(6): 887-896, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28664668

RESUMEN

AIMS: Human papillomavirus (HPV)-related carcinoma with adenoid cystic-like features is a newly described entity of the sinonasal tract. In this study, we evaluated histomorphology, immunophenotype and molecular testing to identify potentially helpful features in distinguishing it from classic adenoid cystic carcinoma (AdCC). METHODS AND RESULTS: We retrospectively collected five HPV-related carcinomas with adenoid cystic-like features and 14 AdCCs of the sinonasal tract. All histological slides were retrieved for morphological evaluation. As comparing with AdCC, HPV-related carcinomas with adenoid cystic-like features were associated with squamous dysplasia of surface epithelium (80% versus 0%, P < 0.01) and the presence of a solid growth pattern (100% versus 29%, P = 0.01), but less densely hyalinized tumour stroma (20% versus 86%, P = 0.02). Squamous differentiation in the invasive tumour was seen in three HPV-related carcinomas with adenoid cystic-like features, two of them showing abrupt keratinization and one with scattered non-keratinizing squamous nests. Diffuse p16 staining in ≥75% of tumour cells was noted in all HPV-related carcinomas with adenoid cystic-like features but in only one AdCC (100% versus 7%, P < 0.01). High-risk HPV testing gave positive results in all HPV-related carcinomas with adenoid cystic-like features (four associated with type 33 and one associated with type 16) but not in AdCCs. MYB rearrangement was tested in four HPV-related carcinomas with adenoid cystic-like features, and all were negative. CONCLUSIONS: This study has further clarified the histological spectrum of this tumour type, and reports the first HPV type 16-related case. Diffuse p16 staining followed by HPV molecular testing is useful in distinguishing HPV-related carcinomas with adenoid cystic features from classic AdCCs.


Asunto(s)
Carcinoma Adenoide Quístico/clasificación , Carcinoma/clasificación , Papillomavirus Humano 16/aislamiento & purificación , Infecciones por Papillomavirus/clasificación , Tonsila Faríngea/patología , Tonsila Faríngea/virología , Adulto , Anciano , Carcinoma/diagnóstico , Carcinoma/patología , Carcinoma/virología , Carcinoma Adenoide Quístico/diagnóstico , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/virología , Femenino , Papillomavirus Humano 16/genética , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Estudios Retrospectivos
3.
Ann Surg Oncol ; 20(11): 3568-74, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23838906

RESUMEN

BACKGROUND: Neck management for cN0 neck remains controversial for T1-2 oral tongue and buccal squamous cell carcinoma (SCC). Increased tumor thickness and perineural invasion (PNI) are two pathologic features that correlated with cervical lymph node (LN) metastasis and poor survival. However, the relationships between these two features remain unclear. METHODS: Detailed histologic reevaluation under hematoxylin and eosin staining was performed in tumors of 212 consecutive patients with T1-2, cN0 oral tongue and buccal SCC. The interrelationships between the impacts of tumor thickness and PNI on cervical LN metastasis and disease-specific survival (DSS) were analyzed. RESULTS: Increased tumor thickness (>6 mm) correlated with higher LN metastasis and poor 5-year DSS rates in univariate analysis. However, only PNI independently predicted both in multivariate analysis (P = 0.004 and P = 0.039, respectively). When stratified by PNI status, increased tumor thickness did not correlate with higher LN metastasis rate in either PNI-negative or PNI-positive groups (P = 0.337 and P = 0.730). Compared to patients with thin tumors (≤6 mm), patient with thick tumors revealed significantly higher LN metastasis rate (41.9 vs. 16.4 %, P = 0.001) and lower 5-year DSS rate (77.5 vs. 93.7 %, P = 0.006) only at the presence of PNI. CONCLUSIONS: PNI can be a major determinant for higher LN metastasis and poor 5-year DSS rates associated with increased tumor thickness in T1-2 oral tongue and buccal SCC. Careful evaluation of PNI should be mandatory in routine pathologic examination, aside from the measurement of tumor thickness.


Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Neoplasias de la Boca/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Nervios Periféricos/patología , Neoplasias de la Lengua/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Neoplasias de la Boca/cirugía , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Nervios Periféricos/cirugía , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/cirugía , Adulto Joven
4.
Ann Surg Oncol ; 19(6): 1995-2002, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22203180

RESUMEN

BACKGROUND: Although perineural invasion (PNI) has been a poor prognostic factor for head and neck cancers, few studies have focused on oral squamous cell carcinoma (OSCC). The independent significance of PNI in early T1-2 OSCC and the benefit of treatment modification based on PNI status have not been assessed. This study investigated the role of PNI in T1-2 OSCC patients, with focus on the controversial issues of neck management and postoperative adjuvant therapy. METHODS: PNI status was re-reviewed under hematoxylin and eosin staining in tumors of 307 consecutive T1-2 OSCC patients. Oncologic and survival outcomes were analyzed by univariate and multivariate analyses. RESULTS: PNI was identified in 84 (27.4%) patients, correlating with several established poor prognostic factors. In multivariate analysis, PNI remained an independent predictor for neck metastasis, neck recurrence, and a worse 5-year disease-specific survival. Elective neck dissection contributed to a significantly better 5-year disease-specific survival only in cN0 patients with PNI-positive tumors (P = 0.0071) but not in those with PNI-negative tumors (P = 0.3566). In low-risk patients who were treated by surgery alone, including neck dissection, the 5-year disease-specific survival rates were almost the same in those with PNI-positive tumors and those with PNI-negative tumors (92.0 vs. 92.9%; P = 0.9104). CONCLUSIONS: Elective neck dissection is indicated for cN0 patients with PNI-positive tumors for the efficacy of improving disease-specific survival as well as neck control. However, low-risk PNI-positive patients who undergo neck dissection do not need postoperative adjuvant therapy, because the residual risk from PNI is minimal.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Neoplasias de la Boca/cirugía , Recurrencia Local de Neoplasia/cirugía , Nervios Periféricos/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Disección del Cuello , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Periodo Posoperatorio , Pronóstico , Tasa de Supervivencia
5.
Cancer Sci ; 102(4): 895-902, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21219537

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) is one prevalent human cancer worldwide. No molecular markers are presently used for predicting prognosis in HNSCC. Krüppel-like factor 4 (KLF4) is a transcription factor with diverse physiological functions, and possesses opposing roles in different human cancers. The expression and roles of KLF4 in HNSCC remain to be elucidated. In this study, immunohistochemical (IHC) analysis of KLF4 in 62 HNSCC was firstly performed. IHC results demonstrated that 42 (67.7%) had decreased KLF4 expression compared with surrounding normal epithelium, while persistent KLF4 expression was demonstrated in 20 (32.3%). The IHC results were further verified by Western blot and real-time PCR analyses to confirm the robustness of staining and interpretation. Interestingly, persistent KLF4 expression independently correlated with a worse disease-specific survival (P = 0.005), especially in patients with advanced disease. In consistent with clinical observation, all five HNSCC cell lines tested revealed a low level of baseline KLF4 expression. Moreover, enforced KLF4 expression in cell line SAS significantly increased in vitro migration/invasion abilities, multi-drug resistance, and in vivo tumorigenicity. These results clearly illustrate that persistent KLF4 expression predicts poor prognosis and confers aggressiveness in HNSCC. Our data therefore provides valuable information that HNSCC with persistent KLF4 expression might require intensified combination treatment in future practice.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Animales , Western Blotting , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/secundario , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Progresión de la Enfermedad , Docetaxel , Resistencia a Antineoplásicos/genética , Femenino , Fluorouracilo/administración & dosificación , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Humanos , Técnicas para Inmunoenzimas , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Taxoides/administración & dosificación , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Eur Arch Otorhinolaryngol ; 268(7): 1035-40, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21120660

RESUMEN

Pleomorphic adenomas, or benign mixed tumors, make up 65% of all salivary gland tumors. They also can be found as solid tumors in other parts of the head and neck region, such as the auditory canal, the eyelids, and the orbital area. In this study, we investigated extra-major salivary gland pleomorphic adenomas of the head and neck region retrospectively at a tertiary care center. Between March 1998 and June 2009, 37 patients underwent primary surgery for extra-major salivary gland pleomorphic adenoma of the head and neck. The duration of symptoms, radiographic findings, operative procedures, and pathologic findings were documented. Of the 37 patients enrolled, 22 were male and 15 were female, with a median age of 57 years. Tumors were found in the soft palate, hard palate, nasopharynx, orbital area, trachea, buccal mucosa, cheek, nasal septum, upper lip, lower eyelid, and external auditory canal. Cellular variant of the pleomorphic adenoma was found in four patients, while the remaining patients presented with the classic variant. No myxoid subgroup was noted in our study. Carcinoma ex pleomorphic adenoma was observed only in one patient for whom radical surgery was performed. Twenty-eight patients (76%) had long-term follow-ups, with the average follow-up period being 4.5 years. Local recurrence was observed in three patients, and they underwent revision surgery during the follow-up period. Our results indicate that extra-major salivary gland pleomorphic adenomas are most commonly found in the soft palate. Wide excision was the treatment of choice, although its efficacy might be compromised with cosmetics and functional structures of the head and neck. Therefore, long-term follow-up of patients is necessary.


Asunto(s)
Adenoma Pleomórfico/patología , Adenoma Pleomórfico/cirugía , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/cirugía , Recurrencia Local de Neoplasia/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/terapia , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
7.
Sci Rep ; 11(1): 19770, 2021 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-34611254

RESUMEN

Postoperative adjuvant therapy has been indicated by advanced T classification for T3-4 oral squamous cell carcinoma (OSCC) and the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) in treatment for T3-4 OSCC remains unclear. Ninety-eight cumulative patients with T3-4 OSCC who underwent curative surgery between Jan 2002 and Dec 2010 were recruited and analyzed. Twenty-seven (27.6%) patients were PNI/LVI double positive. PNI/LVI double positive demonstrated independent predictive values for higher neck metastasis (LN+), higher distant metastasis (DM) and low 5-year disease-specific survival (DSS) rates (p < 0.001, p = 0.017, and p < 0.001, respectively) after controlling for other pathologic features of the primary tumors. A high DM rate of 33.3% was noted in PNI/LVI double-positive patients. Among the PNI/LVI double negative, single positive to double positive subgroups, increasing LN+, DM rates and decreasing DSS rate were observed. Among the 44 LN+ patients, PNI/LVI double positive remained associated with a markedly high DM rate of 42.9% and a poor 5-year DSS of 27.7%. PNI/LVI double positive plays important roles in prognostication and potential clinical application for T3-4 OSCC by independently predicting LN+, DM, and poor DSS, and can be used as a good marker to select DM high-risk patients for novel adjuvant therapy trials.


Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/terapia , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/terapia , Análisis Multivariante , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Vigilancia en Salud Pública , Análisis de Supervivencia
8.
Carcinogenesis ; 30(8): 1443-51, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19483191

RESUMEN

Decoy receptor 3 (DcR3), a member of tumor necrosis factor receptor superfamily, has been implicated in tumorigenesis through its abilities to modulate immune responses and induce angiogenesis. Epstein-Barr virus (EBV), a ubiquitous gamma-herpesvirus, is associated with malignancies including nasopharyngeal carcinoma (NPC). Previous studies show that DcR3 is overexpressed in EBV-positive lymphomas and Rta, an EBV transcription activator, can upregulate DcR3 in Burkitt lymphoma cell lines. However, DcR3 expression has not been demonstrated in EBV-associated NPC nor have there been any EBV latent genes linked to DcR3 upregulation. Here, we showed DcR3 was overexpressed in NPC. Higher DcR3 expression score and DcR3-positive rate were found in metastatic NPC than in primary NPC tissues, suggesting DcR3 may enhance cell metastatic potential. This hypothesis is supported by our observation that NPC HONE-1 cells overexpressing DcR3 exhibited significant higher migration and invasion abilities in vitro. We found besides Rta, EBV latent membrane protein (LMP) 1 can upregulate DcR3 via nuclear factor-kappaB and phosphatidylinositol 3-kinase-signaling events. Approximate 75% of LMP1-positive NPC tissues overexpressed DcR3, suggesting LMP1 may enhance DcR3 expression in vivo. Data herein suggested that increasing DcR3 expression by LMP1 not only helps EBV-associated cancer cells gain survival advantage by preventing host immune detection but also increases the chance of cancer metastasis by enhancing cell migration and invasion. All these DcR3-mediated events facilitate normal cells to gain cancer hallmarks.


Asunto(s)
Movimiento Celular , Infecciones por Virus de Epstein-Barr/patología , Regulación de la Expresión Génica/fisiología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Miembro 6b de Receptores del Factor de Necrosis Tumoral/genética , Proteínas de la Matriz Viral/fisiología , Western Blotting , Inmunoprecipitación de Cromatina , Ensayo de Inmunoadsorción Enzimática , Infecciones por Virus de Epstein-Barr/metabolismo , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/fisiología , Humanos , Técnicas para Inmunoenzimas , Luciferasas/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Neoplasias Nasofaríngeas/virología , Invasividad Neoplásica , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba , Latencia del Virus
9.
Otolaryngol Head Neck Surg ; 160(4): 635-641, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30558519

RESUMEN

OBJECTIVE: Perineural invasion (PNI) has been an established poor prognostic feature for T1-T2 oral squamous cell carcinoma (OSCC). Different presentations and amounts of PNI are commonly observed, but PNI is currently recorded as being present or absent. This study asked whether the quantification of PNI provides additional information for early OSCC. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral medical center. SUBJECTS AND METHODS: Pathologic reevaluations were performed for 314 patients with T1-T2 OSCC who underwent curative surgery from June 2001 to August 2009. A novel parameter, PNI focus number, was defined for PNI quantification. With 5 PNI foci as the cutoff, patients were categorized into 3 groups: no PNI (0 PNI foci), low PNI (PNI foci, 1-5), and high PNI (PNI foci >5). Rate of cervical lymph node metastasis (LN+), 5-year disease-specific survival (DSS), and 5-year overall survival (OS) were analyzed among these groups. RESULTS: PNI focus number independently predicted for LN+, poor DSS, and poor OS in multivariate analysis after controlling for T classification, lymphovascular invasion, differentiation, margin, and tumor thickness. The 5-year DSS demonstrated a dose-dependent decrease among the 3 groups (no PNI, 88.6%; low PNI, 75.2%; high PNI, 33.8%; P < .001). Moreover, the 5-year DSS of the high PNI group was significantly worse than that of the low PNI group. CONCLUSION: PNI focus number can be a novel parameter for PNI quantification in early OSCC. Although optimal quantification methods still require further investigation, this study offers clear clinical support for the nerve-tumor interaction hypothesis and advocates further mechanistic research for the exploration of PNI-related treatment concepts for OSCC.


Asunto(s)
Carcinoma de Células Escamosas/secundario , Neoplasias de la Boca/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/terapia , Invasividad Neoplásica , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
10.
Int J Cancer ; 122(2): 377-86, 2008 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-17918157

RESUMEN

We recently reported that low Nm23-H1 expression of primary oral squamous cell carcinoma (OSCC) was correlated with the occurrence of lymphatic metastasis. However, little is known about whether Nm23-H1 level of metastatic tumors in the cervical lymph nodes is reduced in comparison with primary oral cancers and its significance for patients' prognosis. By immunohistochemistry, we analyzed the Nm23-H1 expression in 52 pairs of OSCC specimens from primary oral cancers and their metastatic lymph nodes. Western blot analysis further confirmed the immunohistochemical interpretation. To verify the effects of Nm23-H1 on cell migration and invasion, we established several stable clones derived from a human OSCC cell line (SAS) by knockdown and overexpression. Wound-healing closure, transwell migration and invasion assays were performed to determine cell motility, migratory and invasive activities. Western blot analysis was carried out to evaluate cyclin A expression of OSCC cells with the altered Nm23-H1 levels following knockdown and overexpression. By immunohistochemistry, Nm23-H1 expression of metastatic lymph nodes was significantly lower than that of their primary oral cancers, supporting a role of Nm23-H1 in metastasis suppression. Negative Nm23-H1 interpretation of OSCC specimens, in either primary oral cancers or metastatic lymph nodes, indicated a poor survival outcome of patients. On the basis of in vitro studies of Nm23-H1 knockdown and overexpression, we demonstrated an inverse correlation between Nm23-H1 expression and the invasiveness of OSCC cells. Moreover, we observed the concomitant reduction in Nm23-H1 and cyclin A levels of metastatic tumors in both results of in vitro OSCC cells and ex vivo tumor specimens.


Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Regulación Neoplásica de la Expresión Génica , Ganglios Linfáticos/metabolismo , Neoplasias de la Boca/metabolismo , Nucleósido Difosfato Quinasas NM23/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/diagnóstico , Línea Celular Tumoral , Ciclina A/metabolismo , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico , Metástasis de la Neoplasia
11.
Am J Clin Pathol ; 130(4): 535-42, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18794045

RESUMEN

A series of 76 cases of gastrointestinal tract endocrine tumors, including 21 poorly differentiated endocrine carcinomas (PDECs, small cell carcinomas) and 55 well-differentiated endocrine neoplasms (WDENs, carcinoids), 18 metastatic and 37 nonmetastatic rectal carcinoids, were examined by immunohistochemical analysis for p16INK4a, cyclin D1, and retinoblastoma protein (pRB) expression. Overexpression of p16INK4a was noted in 16 (76%) of the PDECs and none of the WDENs (P < .0001). Loss of pRB expression was demonstrated in 14 (67%) of the PDECs and 17 (31%) of the WDENs (P = .004). Overexpression of cyclin D1 was noted in 49 (89%) of the WDENs and 3 (14%) of the PDECs (P < .0001). Loss of pRB expression was noted in 11 (61%) of 18 metastatic WDENs and only 6 (16%) of 37 nonmetastatic WDENs (P = .001). The p16INK4a/cyclin D1/pRB pathway was altered in gastrointestinal tract endocrine tumors, and the loss of expression of pRB may be helpful in identifying patients at high risk of metastasis in rectal WDENs.


Asunto(s)
Ciclina D1/biosíntesis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Neoplasias Gastrointestinales/metabolismo , Tumores Neuroendocrinos/metabolismo , Proteína de Retinoblastoma/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias Gastrointestinales/patología , Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/patología
12.
Ann Otol Rhinol Laryngol ; 117(3): 201-6, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18444480

RESUMEN

OBJECTIVES: Hypopharyngeal squamous cell carcinoma (HPSCC) usually presents at an advanced stage. Although chemoradiotherapy has become more popular in treating HPSCC in recent years, surgery with postoperative adjuvant therapy still plays an important role. The purpose of this study was to identify the clinicopathologic factors that predict survival in patients with HPSCC who underwent surgical treatment. METHODS: Between 1986 and 1995, 94 previously untreated HPSCC patients who underwent surgery with or without postoperative radiotherapy were enrolled. The surgical specimens were reexamined by a single pathologist. The clinicopathologic parameters and prognostic data were analyzed. RESULTS: With a median follow-up of 50 months, the 5-year overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) were 47%, 60%, and 58%, respectively. Thirty-seven patients (39%) had tumor recurrence. The level of lymph node metastasis was an independent factor in OS, DSS, and RFS. Neck biopsy before surgery, tumor involvement of more than 1 subsite, and extracapsular spread were independent factors in DSS, as was lymphovascular permeation in RFS. CONCLUSIONS: The level of cervical lymph node metastasis is the only independent prognostic factor in OS, DSS, and RFS. The addition of postoperative chemoradiotherapy may benefit high-risk cases.


Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Neoplasias Hipofaríngeas/mortalidad , Neoplasias Hipofaríngeas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Carcinoma de Células Escamosas/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hipofaríngeas/patología , Laringectomía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Disección del Cuello , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Faringectomía , Radioterapia Adyuvante
13.
J Chin Med Assoc ; 71(10): 546-8, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18955192

RESUMEN

Iris melanocytoma is a rare melanocytic nevus with distinctive clinical and pathologic features. Secondary glaucoma may develop rapidly and respond poorly to glaucoma medication in some cases. However, few data are available in the literature with respect to the appropriate treatment for refractory glaucoma associated with iris melanocytoma. Herein, we present a 28-year-old man with blurred vision and an elevated intraocular pressure (IOP) of 40 mmHg in his right eye while on multiple glaucoma medications. A dark brown lobulated iris mass with surrounding small pigmented lesions was noted between the 4 and 5:30 o'clock positions. Sector iridectomy was performed and pathologic examination revealed an iris melanocytoma. After surgery, antiglaucomatous medications still failed to control IOP. The patient then underwent diode laser transscleral cyclophotocoagulation (TSCP). At the last follow-up of 15 months, IOP had returned to normal without the need for medication.


Asunto(s)
Glaucoma/cirugía , Neoplasias del Iris/complicaciones , Coagulación con Láser/métodos , Nevo Pigmentado/complicaciones , Adulto , Glaucoma/etiología , Humanos , Masculino , Esclerótica/cirugía
14.
Medicine (Baltimore) ; 97(11): e0095, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29538201

RESUMEN

RATIONALE: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. We present the first case of advanced SDC of the minor salivary gland arising from the supraglottis and review the literature on the clinicopathologic characteristics and prognosis of SDC. PATIENT CONCERNS: A 59-year-old male patient with progressive difficulty in swallowing and a muffled voice for 2 months. DIAGNOSES: The patient was diagnosed with SDC arising from the supraglottis with extensive tumor invasion into the subsites of the larynx and pharynx. INTERVENTIONS: Due to impending airway obstruction, the patient underwent CO2 laser debulking surgery. In addition to local disease, lymph node and distant metastases were also noted at diagnosis and concurrent chemoradiation therapy was arranged. OUTCOMES: Laryngeal function was preserved and tracheostomy was avoided. The patient has survived for >1 year after the initial diagnosis. LESSONS: SDC is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. Here we presented the first case of advanced SDC of the minor salivary gland arising from the supraglottis that was treated with CO2 laser debulking surgery followed by concurrent chemoradiation therapy. Due to their rarity, further studies are required to establish the most effective treatment protocol for advanced SDC.


Asunto(s)
Carcinoma , Quimioradioterapia/métodos , Procedimientos Quirúrgicos de Citorreducción , Laringe , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales , Glándulas Salivales Menores/patología , Obstrucción de las Vías Aéreas/etiología , Obstrucción de las Vías Aéreas/cirugía , Carcinoma/patología , Carcinoma/fisiopatología , Carcinoma/terapia , Procedimientos Quirúrgicos de Citorreducción/instrumentación , Procedimientos Quirúrgicos de Citorreducción/métodos , Humanos , Laringe/patología , Laringe/fisiopatología , Laringe/cirugía , Láseres de Gas/uso terapéutico , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/fisiopatología , Neoplasias de las Glándulas Salivales/terapia , Resultado del Tratamiento
15.
AJR Am J Roentgenol ; 189(5): W254-61, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17954621

RESUMEN

OBJECTIVE: Basal cell adenoma is a rare benign epithelial tumor of the salivary gland. The objective of this study is to present the CT findings of parotid basal cell adenoma. We also compare CT findings of basal cell adenoma with those of pleomorphic adenoma, the most common parotid tumor, to determine whether any features on CT can help differentiate these two entities. CONCLUSION: Basal cell adenomas of the parotid gland are located chiefly in the superficial lobe. They are generally round, well-circumscribed tumors that show heterogeneous enhancement on CT. The age of the patient and the attenuation on unenhanced and contrast-enhanced CT may help in differentiating basal cell adenoma from pleomorphic adenoma of the parotid gland.


Asunto(s)
Adenoma Pleomórfico/diagnóstico por imagen , Adenoma/diagnóstico por imagen , Neoplasias de la Parótida/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad
16.
Am J Clin Pathol ; 126(6): 856-65, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17074692

RESUMEN

This study was designed to determine the expression of p16, p53, and CD117 in gastrointestinal tract endocrine tumors. Immunohistochemical studies of p16, p53, and CD117 were performed in 57 gastrointestinal tract endocrine tumors, including 22 poorly differentiated endocrine carcinomas (PDECs) and 35 well-differentiated endocrine tumors (WDETs). Overexpression of p16 and p53 was observed in 16 (73%) and 10 (45%) of the PDECs, respectively, whereas only 1 WDET showed overexpression of p53 and none showed overexpression of p16. A total of 18 (82%) of the PDECs showed overexpression of p16 or p53 proteins. This is closely associated with PDEC (P < .0001). By using overexpression of p16 or p53 as the criteria for PDEC, the sensitivity and specificity are 81.8% and 97.1%, respectively, with positive and negative predictive values of 94.7% and 89.5%, respectively. CD117 was not detected in any of the 57 gastrointestinal endocrine tumors by immunohistochemical analysis.


Asunto(s)
Tumor Carcinoide/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Neoplasias Gastrointestinales/metabolismo , Proteínas Proto-Oncogénicas c-kit/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Tumor Carcinoide/secundario , Femenino , Neoplasias Gastrointestinales/patología , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas
17.
Clin Cancer Res ; 11(15): 5410-6, 2005 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-16061855

RESUMEN

PURPOSE AND EXPERIMENTAL DESIGN: The etiologic association and prognostic significance of mismatch repair gene/protein alterations have never been examined in nonsmoking lung cancer. Therefore, we investigated protein expression and promoter hypermethylation of hMLH1 and hMSH2 genes in the tumor specimens from 105 nonsmoking female non-small cell lung cancer (NSCLC) patients. Immunohistochemistry and restriction enzyme-based multiplex PCR were used to examine the protein expression and promoter hypermethylation, respectively. The occurrence of gene/protein alteration for each gene was compared with the patients' clinicopathologic variables as well as the overall survival and cancer-specific survival rates. RESULTS: Protein expression alteration and promoter hypermethylation were observed in 66% to 67% and 30% to 34% of tumor specimens for hMLH1 and hMSH2 genes, respectively. Loss of hMLH1 and hMSH2 protein expression was significantly associated with their promoter hypermethylation (P < 0.0001 and P = 0.049). The overall survival and cancer-specific survival rates were significantly lower in patients with promoter hypermethylation of hMSH2 gene than in those without hypermethylation (P = 0.038 and P = 0.004). The poor prognosis was still especially significant in adenocarcinoma (P = 0.035 and P = 0.061) and early-stage NSCLC patients (P = 0.067 and P = 0.041). CONCLUSION: Our data suggest that hMLH1 is the major altered mismatch repair gene involved in nonsmoking NSCLC tumorigenesis and that promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation. In addition, promoter methylation of the hMSH2 gene may be a potential prognostic factor in nonsmoking female lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Regiones Promotoras Genéticas , Adulto , Anciano , Enzimas de Restricción del ADN/química , Enzimas de Restricción del ADN/farmacología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Metástasis de la Neoplasia , Reacción en Cadena de la Polimerasa , Pronóstico , Fumar , Factores de Tiempo , Resultado del Tratamiento
18.
J Chin Med Assoc ; 69(7): 322-5, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16903646

RESUMEN

BACKGROUND: Salivary gland carcinomas of the larynx are rare, and account for < 1% of laryngeal malignancy. The purpose of this study is to review our management experience of salivary gland carcinomas of the larynx in Taipei Veterans General Hospital and to compare it with other major existing series. METHODS: From 1981 to 2000, 11 patients with laryngeal salivary gland carcinomas treated in Taipei Veterans General Hospital were included in this study. Their demographic data, treatment modalities, survival, and failure pattern, obtained by review of medical records, were analyzed. RESULTS: All 11 patients were male. Median follow-up period was 95 months (range, 18-181 months). The 5-year overall survival rate of all patients was 71%, and the 5-year disease-specific survival rate was 83%. CONCLUSION: The mainstay treatment of laryngeal salivary gland carcinomas in these cases was surgery or surgery with postoperative radiotherapy. The survival rate was satisfactory and similar to that of squamous cell carcinoma of the larynx.


Asunto(s)
Neoplasias Laríngeas/terapia , Neoplasias de las Glándulas Salivales/terapia , Anciano , Anciano de 80 o más Años , Humanos , Neoplasias Laríngeas/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias de las Glándulas Salivales/mortalidad , Tasa de Supervivencia
19.
J Chin Med Assoc ; 69(3): 120-4, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16599017

RESUMEN

BACKGROUND: Sarcomas of the larynx are rare neoplasms that constitute less than 1% of laryngeal malignancies. A Medline search found no large series focusing on laryngeal sarcomas. We reviewed the cases of laryngeal sarcomas treated in our cancer center and compared our experiences and treatment results with those from other centers. METHODS: A retrospective review of 10 patients with laryngeal sarcoma treated in our institute between 1980 and 2000 was done to identify tumor characteristics, therapeutic modalities, and treatment outcomes. RESULTS: The patients showed a male predominance (9/10) and presented 8 types of pathology. Nine patients underwent surgery, including 2 total laryngectomy, 4 partial laryngectomy, and 3 endoscopic laser cordectomy. During a median follow-up of 92 months, the 5-year overall survival and disease-specific survival were 76% and 90%, respectively. Two patients developed recurrence, including 1 local recurrence and 1 distant metastasis. CONCLUSION: Surgical intervention was the first choice in the treatment of laryngeal sarcomas. The prognosis is relatively good when compared with sarcoma originating from other anatomic sites.


Asunto(s)
Neoplasias Laríngeas/cirugía , Sarcoma/cirugía , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/radioterapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Sarcoma/mortalidad , Sarcoma/radioterapia , Tasa de Supervivencia
20.
Oral Oncol ; 61: 115-9, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27688113

RESUMEN

OBJECTIVES: Perineural invasion (PNI) is an established poor prognostic pathological feature for oral squamous cell carcinoma (OSCC). The purpose of this study was to analyze the role of pretreatment parameters in predicting PNI for OSCC. MATERIALS AND METHODS: We prospectively enrolled into our study 102 newly diagnosed OSCC patients, who were surgically treated from 2011 to 2012. Before treatment, patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N35 and the visual analogue scale (VAS) for cancer pain. Pathological examination was performed to ascertain PNI status in all patients. Patients were divided into two groups, those with PNI and without PNI. Pretreatment parameters were compared between the two groups. RESULTS: In univariate analysis, clinical T classification (P<0.001), painkiller use (P=0.001), problem with social eating (P<0.001) and social contact (P=0.002), VAS scores of primary pain (P<0.001) and referred pain (P=0.004) were found to be associated with PNI. Multivariate logistic regression analysis further revealed VAS score of primary pain (P=0.001, OR 2.014) and T3-4 classification (P=0.014, OR 6.422) were independent predictors of PNI. A regression equation incorporating pretreatment pain was developed to predict the probability of having PNI. CONCLUSION: PNI can be predicted by higher pretreatment VAS score of primary pain, as well as more advanced clinical T classification. Careful evaluation of pretreatment pain of primary tumor can thus be helpful in improving treatment decision making for OSCC.


Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Dolor/etiología , Nervios Periféricos/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
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