RESUMEN
In sinonasal squamous cell carcinoma (SNSCC), the prognostic relevance of p16INK4a (p16) expression has been reported rarely. This study aims to examine the immunohistochemical expression of p16 and investigate the possibility of p16 as a prognostic factor for SNSCC. The medical records of 173 individuals with SNSCC between 2010 and 2022 were retrospectively reviewed. The researchers examined patients' demographics, p16 status, staging, tumor histological subtypes, treatment details, recurrence, metastasis, and survival outcomes. p16 was found in 22.0% (38/173) of SNSCC patients, and there was no difference between inverted papilloma-SNSCC (19.6%) and de novo SNSCC (23.0%). p16 status did not correlate with all the cases' age, gender, clinical stage, or therapy features. p16-positive patients had a considerably superior 5-year overall survival (OS) rate (80.7% vs. 57.5%, p=0.039) and a slight tendency in progression-free survival (PFS) rate (68.1% vs. 52.0%, p=0.15), except in stage T4b cases. In maxillary sinus lesions, p16-positive SNSCC had a better 5-year OS (87.4% vs. 49.2%, p=0.03) rate and PFS (79.1% vs. 40.7%, p=0.01) rate than p16-negative SNSCC. Among patients without skull base involvement (82.9% vs. 57.7%, p=0.037) or orbital invasion (86.9% vs. 57.3%, p=0.02), p16-positive SNSCC confers benefits in OS rates more than p16-negative SNSCC. Immunohistochemical p16 expression may be a predictive predictor in individuals with maxillary sinus SCC, non-T4b stage, without skull base involvement, and without orbital invasion.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de los Senos Paranasales , Humanos , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de los Senos Paranasales/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina , PronósticoRESUMEN
PURPOSE: To study the prevalence of nodal metastases in sinonasal adenoid cystic carcinoma (SNACC) and to evaluate whether prophylactic neck irradiation (PNI) should be performed in patients with clinical N0 (cN0) disease. PATIENTS AND METHODS: Between April 1992 and November 2020, 166 patients with SNACC who had undergone radiotherapy at our department were retrospectively analyzed. The median follow-up time was 71.3 months. RESULTS: Among 166 cases of SNACC, a total of 13 (7.8%) had retropharyngeal or cervical nodal metastasis and 93% (12/13) cases occurred in patients with advanced T stage (T3-T4). Levels VIIa, Ib, and IIa were the most common sites of initial nodal involvement. Only 1.2% (2/166) of patients presented late neck recurrence. Lymph node metastasis independently predicted a poor progression-free survival (PFS) (P = 0.017) but had no impact on overall survival (OS) (P = 0.38). PNI was performed on 36% (55/153) of cN0 patients. The OS (P = 0.42), PFS (P = 0.59), nodal recurrence-free survival (NRFS) (P = 0.46) and distant metastasis-free survival (DMFS) (P = 0.63) rates showed no significant difference between cases with and without PNI. Furthermore, cN0 patients with T4b (P = 0.53; P = 0.61), tumor origin from maxillary sinus (P = 0.55; P = 0.53) or nasopharynx involvement (P = 0.56; P = 0.60) showed no extended OS or PFS associated with PNI. CONCLUSIONS: Regardless of the T stage or the site of origin, prophylactic neck irradiation (PNI) for cN0 patients did not provide any benefit on OS and PFS, suggesting that its application on such patients is not warranted unless there is clinical suspicion.
Asunto(s)
Carcinoma Adenoide Quístico , Carcinoma , Senos Paranasales , Carcinoma/patología , Carcinoma Adenoide Quístico/radioterapia , Humanos , Metástasis Linfática , Estadificación de Neoplasias , Senos Paranasales/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Early diagnosis of nasopharyngeal carcinoma (NPC) needs more reliable biomarkers. The aim of this study was to investigate serum cytokeratin 19 fragment 21.1 (CYFRA21-1) as an NPC biomarker based on data from a large sample. METHODS: From October 2010 to February 2014, 529 subjects were enrolled and divided into three groups-NPC group (n = 274), healthy control group (n = 175) and nasal inflammatory disease group (n = 80). Serum CYFRA21-1 levels were measured prior to radiotherapy/chemoradiotherapy, and their associations with T, N, and clinical classification were determined. Receiver operating characteristic curve analysis was performed to discriminate the NPC group from the healthy control and nasal inflammatory disease groups. Three Epstein-Barr virus (EBV) antibodies and their correlations with serum CYFRA21-1 levels were analyzed. RESULTS: Pretreatment serum CYFRA21-1 levels were significantly elevated in the NPC group compared with the other groups (p < 0.01), Furthermore, serum CYFRA21-1 levels decreased significantly after radiotherapy (p < 0.01). Serum CYFRA21-1 levels were closely related to T, N, and clinical classifications. The area under the curve, sensitivity and specificity of the serum CYFRA21-1 levels in the NPC patients were 0.89, 0.87 and 0.83, respectively. Strong correlations were observed between serum CYFRA21-1 levels and EBV antibodies. CONCLUSION: Serum CYFRA21-1 may be a reliable and effective biomarker for NPC.
Asunto(s)
Anticuerpos Antivirales/sangre , Antígenos de Neoplasias/sangre , Quimioradioterapia/métodos , Queratina-19/sangre , Neoplasias Nasofaríngeas , Adulto , Biomarcadores de Tumor/sangre , Carcinoma , Femenino , Herpesvirus Humano 4/inmunología , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/virología , Estadificación de Neoplasias , Evaluación del Resultado de la Atención al Paciente , Pronóstico , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadística como AsuntoRESUMEN
The serine/threonine kinase mammalian target of rapamycin (mTOR) promotes cell survival and proliferation, and is constitutively activated in head and neck squamous cell carcinoma (HNSCC). Thus mTOR is an important target for drug development in this disease. Here we tested the anti-tumor ability of AZD8055, the novel mTOR inhibitor, in HNSCC cells. AZD8055 induced dramatic cell death of HNSCC lines (Hep-2 and SCC-9) through autophagy. AZD8055 blocked both mTOR complex (mTORC) 1 and mTORC2 activation without affecting Erk in cultured HNSCC cells. Meanwhile, AZD8055 induced significant c-Jun N-terminal kinase (JNK) activation, which was also required for cancer cell death. JNK inhibition by its inhibitors (SP 600125 and JNK-IN-8), or by RNA interference (RNAi) alleviated AZD8055-induced cell death. Finally, AZD8055 markedly increased the survival of Hep-2 transplanted mice through a significant reduction of tumor growth, without apparent toxicity, and its anti-tumor ability was more potent than rapamycin. Meanwhile, AZD8055 administration activated JNK while blocking mTORC1/2 in Hep-2 tumor engrafts. Our current results strongly suggest that AZD8055 may be further investigated for HNSCC treatment in clinical trials.