Tung-Lung Tsai

Regulation of Excision Repair Cross-Complementation Group 1 by Snail Contributes to Cisplatin Resistance in Head and Neck Cancer

Purpose: We investigated the mechanism and clinical significance of the epithelial-mesenchymal transition (EMT)-induced chemoresistance in head and neck squamous cell carcinoma (HNSCC). Experimental Design: The correlation between the expression of different EMT regulators and chemoresistance genes, such as excision repair cross complementation group 1 (ERCC1), was evaluated in cancer cell lines from the NCI-60 database and four human HNSCC cell lines. Ectopic expression of Snail or short-interference RNA-mediated repression of Snail or ERCC1 was done in HNSCC cell lines. Cell viability was examined for cells after cisplatin treatment. A luciferase reporter assay and chromatin immunoprecipitation were used to identify the transcriptional regulation of ERCC1 by Snail. Immunohistochemical analysis of Snail, Twist1, ERCC1, hypoxia inducible factor-1 α (HIF-1α), and NBS1 were done in samples from 72 HNSCC patients receiving cisplatin-based chemotherapy. Results: The correlation between the expression of Snail and ERCC1 was confirmed in different cell lines, including HNSCC cells. In HNSCC cell lines, overexpression of Snail in the low endogenous Snail/ERCC1 cell lines FaDu or CAL-27 increased ERCC1 expression, and hypoxia or overexpression of NBS1 also upregulated ERCC1. Knockdown of Snail in the high endogenous Snail/ERCC1 cell line OECM-1 downregulated ERCC1 expression and attenuated cisplatin resistance. Furthermore, suppression of ERCC1 in Snail- or NBS1-overexpressing HNSCC cells enhanced sensitivity to cisplatin. Snail directly regulated ERCC1 transcription. In patients with HNSCC, coexpression of Snail and ERCC1 correlated with cisplatin resistance and a poor prognosis. Conclusions: Activation of ERCC1 by Snail is critical in the generation of cisplatin resistance of HNSCC cells. Clin Cancer Res; 16(18); 4561–71. ©2010 AACR.

Risks and clinical implications of perineural invasion in T1‐2 oral tongue squamous cell carcinoma

Risks of perineural invasion (PNI) in T1‐2 oral tongue squamous cell carcinoma (SCC) have not been specifically elucidated.

Effectiveness of narrow band imaging in patients with oral squamous cell carcinoma after treatment

We evaluated the effectiveness of narrow band imaging (NBI) in patients with oral squamous cell carcinoma (OSCC) after treatment.

Positron emission tomography in surveillance of head and neck squamous cell carcinoma after definitive chemoradiotherapy.

We assessed the role of 18F‐fluoro‐deoxy‐glucose positron emission tomography (PET) in detecting head and neck squamous cell carcinoma (HNSCC) after definitive chemoradiotherapy (CRT).

Persistent Krüppel-like factor 4 expression predicts progression and poor prognosis of head and neck squamous cell carcinoma

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. (Cancer Sci 2011; 102: 895–902)

Chemoradiotherapy Laryngeal Preservation for Advanced Hypopharyngeal Cancer

OBJECTIVE Laryngeal preservation is a challenge for the treatment of advanced hypopharyngeal cancer. The objective of this study is to evaluate the results of chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer at a single institute and the impact of treatment factors on prognosis. METHODS The study population consisted of 42 consecutive patients with resectable stage III-IV hypopharyngeal cancer. Patients with T4b tumor, synchronous primary cancer or those treated palliatively were excluded. Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) was performed in 32 (76.2%) patients, whereas primary CCRT was done in the other 10 (23.8%). Patients were grouped according to the dose intensity of chemotherapy and total dose of radiotherapy (RT). RESULTS Grade 3-4 toxicities occurred mostly during CCRT. Thirty-five (83.3%) patients received an optimum dose of cisplatin (CT-optimum), 27 (64.3%) received an optimum dose of RT-optimum and 26 (61.9%) received optimum doses of both (CRT-optimum). CT- and RT-optimum both correlated significantly with better disease-free survival (DFS) (P < 0.001 and = 0.003), overall survival (OS) (P < 0.001 and = 0.004) and laryngeal preservation survival (LPS) (P = 0.01 and 0.04). The 3-year DFS, OS and LPS for CRT-optimum patients were 48.1, 50.0 and 45.6%, respectively. CONCLUSIONS Achievement of optimum treatment dose remains challenging in chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer. Intensive patient care and monitoring by experienced multi-disciplinary teamwork are mandatory. The criteria for selecting patients who will respond to and complete the treatment remain key issues for future investigation.

Localized Amyloid Deposition in the Nasopharynx and Neck, Mimicking Nasopharyngeal Carcinoma with Neck Metastasis

Amyloidosis results from the deposition of amyloid proteins in organs and tissues. Clinically, it can be classified into systemic and localized forms. Here, we report a case of localized amyloidosis of the nasopharynx and neck. The initial presentation was a nasopharyngeal mass, and bilateral neck masses, mimicking nasopharyngeal carcinoma with neck metastasis. Computed tomographic scans of the neck revealed asymmetry between the bilateral nasopharyngeal walls, and multiple radio-opaque masses in both sides of the neck. A nasopharyngeal biopsy was performed and confirmed amyloid deposition. Subsequent neck-mass excision biopsies confirmed that the neck masses were also amyloid deposits. Further laboratory examinations revealed no systemic involvement. There was no disease progression after local excision. Localized amyloidosis in the head and neck is rare, but can have various manifestations that may sometimes mimic neoplasms.

Predictors and timing of recovery in patients with immediate facial nerve dysfunction after parotidectomy

Identification of predictors for permanent facial nerve dysfunction and timing of recovery are important for the management of patients who experience immediate facial nerve dysfunction after parotidectomy.

Epithelioid Hemangioendothelioma of the Nasal Cavity

Epithelioid hemangioendothelioma (EH) is an unusual vascular neoplasm characterized by proliferation of endothelial cells with epithelioid morphology. It has an indolent course, with the potential for recurrence, but rarely metastasizes. The common locations include soft tissue, skin, viscera and bone. We present an unusual case of EH in the nasal cavity and describe the clinical characteristics, histopathologic findings, differential diagnosis and management. The 25-year-old male patient initially presented with an 8-month history of intermittent epistaxis. Nasal endoscopy revealed a vascular tumor involving the nasal cavity. The tumor was excised and the final histopathologic diagnosis was consistent with EH. EH in the head and neck is extremely rare. Wide excision is the treatment of choice, and regular follow-up is suggested due to the potential for recurrence. Definitive diagnosis depends on histopathologic and immunohistochemical features.

Methotrexate and Leucovorin Double-modulated 5-Fluorouracil Combined with Cisplatin (MPFL) in Metastatic/Recurrent Head and Neck Cancer

Background: To determine the efficacy and safety profile of the combination of cisplatin and 5‐fluorouracil modulatedboth by methotrexate and leucovorin in metastatic/recurrent squamous cell carcinoma of the head and neck. Methods: Twenty‐eight patients were treated with cisplatin 40 mg/m2/day continuous infusion for 24 hours on day 1;high‐dose 5‐fluorouracil 2,000 mg/m2/day and leucovorin 100 mg/m2/day continuous infusion for 48 hours on days 1and 2; methotrexate 40 mg/m2/day as a bolus infusion 4 hours before 5‐fluorouracil and leucovorin on day 1. The treat‐ment was repeated every 2 weeks in a cycle. Results: The overall response rate was 25%, and 14% of the patients achieved stable disease status. Subgroup analy‐sis demonstrated significantly improved overall survival in the disease‐control group (12.0 months vs. 5.3 months, p < 0.001). Only 3 (10.7%) patients developed grade 3–4 neutropenia, and none developed grade 3–4 non‐hematologictoxicity. Conclusion: This multiagent‐containing regimen has an excellent safety profile and improved survival in disease‐controlgroup of patients with metastatic/recurrent squamous cell carcinoma of the head and neck.