Young Soo Rho

SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma

Background:Head and neck squamous cell carcinomas (HNSCCs) display cellular heterogeneity and contain cancer stem cells (CSCs). Sex-determining region Y [SRY]-box (SOX)2 is an important regulator of embryonic stem cell fate and is aberrantly expressed in several types of human tumours. Nonetheless, the role of SOX2 in HNSCC remains unclear.Methods:We created cells ectopically expressing SOX2 from previously established HNSCC cells and examined the cell proliferation, self-renewal capacity, and chemoresistance of these cells compared with control cells. In addition, we knocked down SOX2 in primary spheres obtained from HNSCC tumour tissue and assessed the attenuation of stemness-associated traits in these cells in vitro and in vivo. Furthermore, we examined the clinical relevance of SOX2 expression in HNSCC patients.Results:SOX2 is aberrantly expressed in primary tissue of HNSCC patients but not in healthy tissue. SOX2 expression correlated with tumour recurrence and poor prognosis of HNSCC patients. Ectopic expression of SOX2 induced cell proliferation via cyclin B1 expression and stemness-associated features, such as self-renewal and chemoresistance. In addition, a knockdown of SOX2 in HNSCC CSCs attenuated their self-renewal capacity, chemoresistance (through ABCG2 suppression), invasion capacity (via snail downregulation), and in vivo tumorigenicity.Conclusions:These results suggest that SOX2 may have important roles in the ‘stemness’ and progression of HNSCC. Targeting SOX2-positive tumour cells (CSCs) could be a new therapeutic strategy in HNSCCs.

High mobility group HMGI(Y) protein expression in head and neck squamous cell carcinoma

Conclusion. We conclude that increased expression level of the high mobility group I (HMGI(Y)) is closely associated with malignant transformation in head and neck squamous cell carcinomas (HNSCCs), and the measurement of HMGI(Y) levels in HNSCCs may be useful as a prognostic marker. Objectives. To investigate whether HMGI overexpression is observed in HNSCCs, and its value as a prognostic marker in HNSCCs. Materials and methods. HMGI(Y) expression was determined at the protein level by immunohistochemisty using a HMGI(Y)-specific antibody and RT-PCR in 10 surgically resected specimens of non-neoplastic tissue (normal palatal tissue) and 40 HNSCCs. We also evaluated the association of HMGI(Y) overexpression within clinicopathologic parameters, i.e. clinical stage, pathologic grade, status of cervical lymph node metastasis, recurrence rate. Results. Expression of HMGI(Y) by immunohistochemical staining was observed in 35 of 40 (87.5%) HNSCC samples, whereas normal mucosa and/or the mucosa adjacent to the tumor tissue showed negative or weakly positive staining (p<0.05). Semi-quantification of HMGI(Y) by RT-PCR was 2.98±2.24 in cancer and 0.47±0.25 in normal tissue (p<0.001). High expression of HMGI(Y) was observed in recurrent cases, compared with non-recurrent cases (p<0.05). However, no significant correlation was observed between the levels of HMGI(Y) expression and other clinical factors such as clinical stage, pathologic grade, and status of cervical lymph node metastasis.

Necrotizing sialometaplasia accompanied by adenoid cystic carcinoma on the soft palate.

Necrotizing Sialometaplasia (NS) is a benign, self-limiting inflammatory disease of the mucus-secreting glands, and this illness mainly involves the minor salivary glands. The significance of NS resides in its clinical and histopathological resemblance to malignancy. We present here a case of necrotizing sialometaplasia on the soft palate, and this was accompanied by adenoid cystic carcinoma. We report here on this case to draw attention to the difficulty for deciding the extent of resecting a malignancy, and especially when the malignancy is simultaneously accompanied by necrotizing sialometaplasia.

Analysis of 120 Pectoralis Major Flaps for Head and Neck Reconstruction

Background A pectoralis major flap is one of the standard tools for the reconstruction of defects of the head and neck. Despite the technical advancement in free tissue transfer in head and neck reconstruction, the benefits of a pectoralis major flap should not be overlooked. The purpose of this study is to evaluate our 17 years of experience in reconstructing defects of the head and neck region using the pectoralis major flap. Methods We retrospectively reviewed the medical records of 112 patients (120 cases) who underwent pectoralis major flap operations for head and neck reconstruction during a period ranging from 1994 to 2010. Results In our series, no total necrosis of the flap occurred. Of the total cases, 30.8% presented with flap-related complications. Major complications occurred in 20% of all of the cases but were then all successfully treated. The male sex was correlated with the occurrence of overall complications (P=0.020) and major complications (P=0.007). Preoperative albumin levels of <3.8 g/dL were correlated with the formation of fistula (P=0.030). Defects of the hypopharynx were correlated with the occurrence of major complications (P=0.019) and the formation of fistula (P=0.012). Secondary reconstructions were correlated with the occurrence of overall complications (P=0.013) and the formation of fistula (P=0.030). Conclusions A pectoralis major flap is still considered to be a safe, versatile one-stage reconstruction procedure in the management of the defects of head and neck and the protection of the carotid artery.

The role of elective neck dissection during salvage surgery in head and neck squamous cell carcinoma.

Abstract Conclusion: As the occult nodal metastasis ratio is low and there is no statistical benefit of elective neck dissection, elective neck dissection is not always necessary during salvage surgery. However, in patients with N positive at initial treatment and cases developing a recurrence within 1 year, elective neck dissection should be considered during salvage surgery. Objectives: The aim of this study was to evaluate the role of ipsilateral or contralateral elective neck dissection during salvage surgery in head and neck squamous cell carcinoma. Methods: A total of 154 node negative and previously undissected heminecks were electively dissected or observed. We estimated the occult metastasis rate in the electively dissected group and compared the regional control rate and disease-specific survival rate between the elective neck dissection group and the observation group. Results: Six of 80 electively dissected heminecks (7.5%) had occult nodal metastasis. When comparing the regional control rate and disease-specific survival rate between the elective neck dissection group and the observation group, there was no statistically significant difference between groups. However, N-positive cases at initial treatment and recurrent cases that developed within 1 year had a significant advantage for elective neck dissection during salvage surgery.

Transforming growth factor β1 enhances stemness of head and neck squamous cell carcinoma cells through activation of Wnt signaling

Transforming growth factor β (TGFβ) ligands, including TGFβ1, are multifunctional cytokines known as key regulators of cell growth, differentiation and inflammation. Dysregulated TGFβ signaling is common in numerous solid tumors, including head and neck squamous cell carcinoma (HNSCC). Previously, TGFβ ligands were also reported to be associated with an enhancement of stemness in glioma stem-like cells. However, their role in HNSCC cancer stem cells (CSCs) has not been explored. The present study demonstrated that TGFβ1 enriches the properties of HNSCC CSCs. TGFβ1 promoted sphere formation and increased stemness-associated gene expression (Oct4 and Sox2) of primary HNSCC CSCs. Additionally, the population of aldehyde dehydrogenase (ALDH)-positive cells was increased subsequent to exogenous treatment of cells with TGFβ1. In addition, following stimulation with TGFβ1, the cells exhibited more resistance to cisplatin and elevated expression of Twist, Snail and Slug. Mechanistically, TGFβ1 acts as an upstream stimulator of Wnt/β-catenin signaling. Collectively, the present findings provide insights toward the development of TGFβ1 signaling inhibition strategies for treating HNSCC CSCs.

ECRG1 and FGFR4 single nucleotide polymorphism as predictive factors for nodal metastasis in oral squamous cell carcinoma

BACKGROUND AND OBJECTIVES The aim of this study was to examine the pattern of SNPs in ECRG1 and FGFR4 gene of oral squamous cell carcinoma, and to evaluate the association between SNPs and prognostic parameters. MATERIALS AND METHODS Total 24 cases of oral squamous cell carcinoma patients were enrolled in this study. We analyzed the pattern of SNPs in ECRG1 and FGFR4 gene using PCR and direct sequence. Also we evaluated the association between SNPs pattern and clinicopathologic parameters of oral squamous cell carcinoma. RESULTS The allele type Arg/Arg in ECRG1 gene was found in 13 (54.2%) patients, Arg/Gln in 11 (45.8%) patients and Gln/Gln in no patient. No clinical or pathological factor was associated with the SNP pattern in ECRG1. The allele types of FGFR4 amino acid 388 in 24 OSCC patients were Arg/Arg (8.3%), Arg/Gly (54.2%) and Gly/Gly (37.5%). No clinical or pathological factor was significantly associated with the SNP pattern except the nodal stage. The patients carrying FGFR4 allele Arg/Arg or Arg/Gly at amino acid 388 were associated with advanced N stage (pathologic N2+N3), compared to Gly/Gly allele carrying group (p=0.009). CONCLUSION This study is the first to describe a SNP pattern of both FGFR4 and ECRG1 gene with OSCC in Asian patients. In this study, FGFR4 Arg allele carrier was associated with higher N stage compared with Gly allele. If the important biological role of FGFR4 and ECRG1 in OSCC can be confirmed in further studies, this might be a rational to consider the evaluation of these genes as a therapeutic target in OSCC.

The Role of Transnasal Esophagoscopy in ENT Office: A Prospective, Multicenter Study in Korea

Objectives The purpose of study was to report the current role of transnasal esophagoscopy (TNE) in Korea. Methods One hundred thirty-seven patients who underwent TNE at Soonchunhyang University Bucheon Hospital (n=69) and Korea University Anam Hospital (n=68) from July 2007 to February 2009 were prospectively analyzed. Laryngopharyngeal reflux disease (LPRD) patients without any response to proton-pump inhibitor (n=102), and patients with complaints that require esophagoscopy as part of their evaluation (n=35) were included in this study; investigation of metachronous lesions or routine follow-up screening of head and neck cancer patients, n=17; dysphagia, n=9; blood tinged saliva, n=4; to determine the cause of vocal fold paralysis as screening tool, n=4; suspicious esophageal foreign body, n=1. Results Fifty-three patients (38.7%) had positive findings on TNE. Positive finding ratio was highest in group of dysphagia (7 among 9 patients, 78%). Forty-two patients (41.1%) were found to have pathology (esophagitis, n=41; esophageal diverticulum, n=1) during the screening examination for LPRD. There were no significant complications in any of the patients. Conclusion TNE is a high-yield diagnostic and therapeutic modality available to otolaryngologists for use on awake patients in the office setting.

Conversion from selective to comprehensive neck dissection: is it necessary for occult nodal metastasis? 5-year observational study.

Objectives To compare the therapeutic results between selective neck dissection (SND) and conversion modified radical neck dissection (MRND) for the occult nodal metastasis cases in head and neck squamous cell carcinoma. Methods Forty-four cases with occult nodal metastasis were enrolled in this observational cohort study. For twenty-nine cases, SNDs were done and for fifteen cases, as metastatic nodes were found in the operative field, conversion from selective to MRNDs type II were done. Baseline data on primary site, T and N stage, extent of SND, extracapsular spread of occult metastatic node and type of postoperative adjuvant therapy were obtained. We compared locoregional control rate, overall survival rate and disease specific survival rate between two groups. Results Among the 29 patients who underwent SND, only one patient had a nodal recurrence which occurred in the contralateral undissected neck. On the other hand, among the 15 patients who underwent conversion MRND, two patients had nodal recurrences which occurred in previously undissected neck. According to the Kaplan Meier survival curve, there was no statistically significant difference for locoregional control rate, overall survival rate and disease specific survival rate between two groups (P=0.2719, P=0.7596, and P=0.2405, respectively). Conclusion SND is enough to treat occult nodal metastasis in head and neck squamous cell carcinoma and it is not necessary to convert from SND to comprehensive neck dissection.

Role of surgery in the management of anaplastic thyroid carcinoma: Korean nationwide multicenter study of 329 patients with anaplastic thyroid carcinoma, 2000 to 2012

The Korean Society of Thyroid Head and Neck Surgery established a nationwide multicenter registry of anaplastic thyroid carcinoma (ATC) and evaluated the prognostic factors and treatment outcomes of ATC.