• Radiation Oncology Journal
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• v.15 no.4
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• pp.321-329
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• 1997

Purpose : It is well known that the risk of lymph nodes metastases to head and neck cancers are influenced by the location and size of the Primary tumor. as well as the degree and types of histological differentiation. However, data on the statistical analyses of lymph node metastases from the head and neck cancers among Korean Population are not available at present. In order to obtain current status of such data, we have analyzed cancer patients at the department of radiation oncology, korea universityhospital for radiation treatment. Materials and Methods : We have evaluated nine-hundred and ninetyseven (997) head and neck cancer Patients who visited to the Department of radiation oncology, between November 1981 to December 1995. After careful physical examinations and CAT scan, Patients were divided into two groups, those with positive lymph node metastases and with negative lymph node metastases. The nodal status were classified according to the TNM system of American Joint Committee on Cancer (AJCC) Besults : Four-hundred and sixteen Patients out of the 997 patients were lymph node positive $(42\%)$ and 581 patients were lymph node negative $(58\%)$ when they were first presented at the department of radiation oncelogy. According to the AJCC classification, the distribution of positive lymph node is as follow: Nl:106 $(25.5\%),\;N2a:100\;(24\%),\;N2b:68\;(16.4\%),\;N2c:69\;(16.6\%),\;3:73\;(15\%).$ respectively. The frequency of lymph node metastases according to the primary sites is as follow : larynx 283 $(28.5\%)$, paranasal sinuses: 182 $(18\%),\;oropharynx:144\;(14.5\%)\;nasopharynx:122(12\%),\;oral\;cavity\;92\;(9\%),\;hypopharynx:71\;(7\%),\;falivary\;gland:58\;(6\%)$ unknown primary:31 $(3\%),\;skin:\;14(2\%)$,. The most frequent Primary site for the positive Iymph node metastases was nasopharynx $(71\%)$ followed by hypopharynx $(69\%),\;oropharynx\;(64\%),\;oral\;cavity\;(39\%)$ The most common histologic type was squamous cell carcinoma (652/997: $65.4\%$). followed by malignant lymphoma $(109/997:11\%)$. Conclusion : Statistical results of lymph node metastases from head and neck cancer at our department were very similar to those obtained from other countries. It is concluded that the location of Primary cancer influences sites of metastases on head and neck, and stage of the primary cancer also influences the development of metastatic lesions. Since the present study is limited on the data collected from one institute. further statistical analyses on Korean cancer Patients are warrented.

• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.182-190
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• 1998

Background: Most of the cancers of maxillary sinus are the squamous variety, but various histopathologic types of malignant tumor can occur in the maxillary sinus. These non-squamous cell tumors have quite different patterns of clinical behavior compared with squamous variety, such as invasive characters, route of metastasis, treatment modality, and so on. Objectives: The authors intend to establish the clinical characteristics and treatment modalities of non-squamous cell tumors of the maxillary sinus. Material and Methods: We experienced 16 cases of non-squamous cell tumors arisen from the maxillary sinus during the 10-year period from 1987 to 1996. We analyzed their clinical features, therapeutic modalities and results with review of literatures. Results: According to AJCC TNM system, 13 patients presented with $T_{1-2}$, 3 with $T_{3-}4$, Two patients were treated with surgery after radiotherapy, 3 patients with surgery after chemotherapy and radiotherapy, 4 patients with chemotherapy and radiotherpy, 5 patients with chemotherapy and radiotherapy after surgery. Conclusion: In cases of adenoid cystic carcinoma, adenocarcinoma and sarcoma, we believe that the best form of therapy is wide surgical excision. If there is microscopic evidence of disease at or close to the resection margin, postoperative radiation was used to achieve better local control. In cases of undifferentiated carcinoma, preoperative chemotherapy and radiation therapy showed improved outcomes.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.179-184
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• 2001

Objective: The role of chemotherapy in locally advanced head and neck cancer has been established in nasopharynx and larynx as definitive therapy and organ preserving therapy, respectively. Oral cavity cancers are relatively uncommon and local recurrence is the main cause of treatment failure. We planned this retrospective study to evaluate the role of neoadjuvant chemotherapy in locally advanced oral cavity cancer patients. Materials and Methods: From 1988 March to 2001 February, locally advanced, previously untreated oral cavity cancer patients who received neoadjuvant chemotherapy were examined. Chemotherapy had been done in the following patients: Histologically proven squamous cell or poorly differentiated carcinoma, stage 3 or 4, and performance state 0-2 patients. Chemotherapy regimen consisted of cisplatin and infusional 5-fluorouracil. Response was evaluated after 2 cycles and in case of no response, definitive local therapy was done; otherwise 3 cycles was done before local treatment. Results: 48 patients were treated and 47 patients were evaluable for responses. Complete response rate was 6.4%(3/47) and partial response 80.0%(38/47), scoring overall response rate of 87.2%. Median time to progression was 27.0 months (95% CI : 0-58months) and overall 5 year survival was 54.8%. 5-year disease-free survival in the patients in remission after local treatment was 51.9%. In multivariate analysis, contributing factor to the survival were response to neoadjuvant chemotherapy and local treatment modalities. Extensive surgery was done in 10 patients and 25 patents (52.1%) was followed up with preserved function. With median follow-up of 57.0 months, 19 recurrences were detected, most of which were local or regional type. Conclusion: Neoadjuvant chemotherapy followed by local treatment in oral cavity cancer showed high response rate and was thought to be effective therapeutic approach especially in view of organ preservation.

• Radiation Oncology Journal
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• v.27 no.2
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• pp.55-63
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• 2009

Purpose: This study was performed to objectively evaluate the rate of tumor response to hypofractionated radiotherapy for advanced squamous cell carcinomas of the head and neck. Materials and Methods: Thirty-one patients with advanced squamous cell carcinoma of the head and neck, who were treated by hypofractionated radiotherapy with 3 Gy per fraction for palliative purpose between 1998 and 2008, were reviewed retrospectively. Every tumor-volume was measured and evaluated from CT (computed tomography) images obtained before and 2~3 months after radiotherapy. The radiation toxicity was assessed during and after radiotherapy. A statistical analysis was performed to investigate overall survival, progressionfree survival, and the prognostic factors for survival and response. Results: The median age of the study patients was 70 years. In addition, 85% of the patients were in stage 4 cancer and 66.7% had an ECOG performance status of 1~2. The mean tumor-volume was 128.4 cc. Radiotherapy was administered with a total dose of 24~45 Gy (median: 36 Gy) over 10~25 days. Twenty-nine patients were treated with 30 Gy or more. The observed complete response rate was 12.9% and the partial response rate was 61.3%. Median survival time was 8.9 months and the 1-year progression-free survival rate was 12.9%. The treatment response rate was confirmed as a prognostic factor in the rate of survival. The primary site, stage, tumor-volume, radiotherapy field and overall radiation-dose showed a significant relationship with survival and treatment response. No grade 4 toxicity was observed during and after radiotherapy. Conclusion: There was an objective tumor-regression in about 74% of patients treated by hypofractionated radiotherapy. Further evaluation is needed to select the appropriate fraction-size and patient who may require the additional radiotherapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.5
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• pp.341-347
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• 2020

Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck cancer. MicroRNAs, as new biomarkers, are recommended for diagnosis and treatment of different types of cancers. Bevacizumab, sold under the trade name Avastin, is a humanized whole monoclonal antibody that targets and blocks VEGF-A (vascular endothelial growth factor A; angiogenesis) and oncogenic signaling pathways. Materials and Methods: This study comprised 50 cases suffering from OSCC and 50 healthy participants. Peripheral blood samples were collected in glass test tubes, and RNA extraction was started immediately. Expression levels of miR-155, miR-191, and miR-494 biomarkers in the peripheral blood of OSCC-affected individuals and healthy volunteers in vivo were evaluated using real-time PCR. The influence of Avastin on the expression levels of the aforementioned biomarkers in vitro and in the HN5 cell line was also investigated. Results: Expression levels of miR-155, miR-191, and miR-494 in the peripheral blood of individuals affected by OSCC were higher than in those who were healthy. Moreover, Avastin at a concentration of 400 μM caused a decrease in the expression levels of the three biomarkers and a 1.5-fold, 3.5-fold, and 4-fold increase in apoptosis in the test samples compared to the controls in the HN5 cell line after 24, 48, and 72 hours, respectively. Conclusion: The findings of this study demonstrate that overexpression of miR-155, miR-191, and miR-494 is associated with OSCC, and Avastin is able to regulate and downregulate the expression of those biomarkers and increase apoptosis in cancerous cells in the HN5 cell line.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4049-4057
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• 2016

Background: High-risk human papillomaviruses (HR-HPV), particularly types 16 and 18, have been found to play an important role in head and neck cancer, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). p16, a cell cycle inhibitor, has been postulated as a surrogate marker for HR-HPV, since p16 is aberrantly overexpressed in such lesions, especially in HR-HPV-positive OPSCC. However, p16 as a surrogate marker for HR-HPV infection in cancers of the oral cavity remains controversial. Objective: The objectives of the study were to investigate the expression of p16 and the presence of HR-HPV in OSCC and oral verrucous carcinoma (VC) and to determine if p16 could be used as a surrogate marker for HR-HPV. Materials and Methods: Forty one formalin-fixed, paraffin-embedded tissues of OSCC (n=37) or VC (n=4) with clinical and histopathologic data of each case were collected. Expression of p16 was determined by immunohistochemistry, focusing on both staining intensity and numbers of positive cells. The presence of HPV types 16 and 18 was detected by polymerase chain reaction (PCR). Descriptive statistics were employed to describe the demographic, clinical, and histopathologic parameters. Associations between p16 overexpression, HR-HPV and all variables were determined by Fisher's exact test, odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In addition, the use of p16 as a surrogate marker for HR-HPV was analyzed by sensitivity and specificity tests. Results: p16 was overexpressed in 8/37 cases (21.6%) of OSCC and 2/4 cases (50%) of VC. HPV-16 was detected in 4/34 OSCC cases (11.8%) and HPV-18 was detected in 1/34 OSCC cases (2.9%). Co-infection of HPV-16/18 was detected in 1/4 VC cases (25%). Both p16 overexpression and HR-HPV were significantly associated with young patients with both OSCC and VC (p<0.05, OR 20, 95% CI 1.9-211.8; p<0.05, OR 23.3, 95% CI 2.4-229.7, respectively). p16 was able to predict the presence of HPV-16/18 in OSCC with 40% sensitivity and 79.3% specificity and in VC with 100% sensitivity and 66.7% specificity, respectively. Conclusions: p16 overexpression was found in 24.4% of both OSCC and VC. HR-HPV, regardless of type, was detected in 15.8% in cases of OSCC and VC combined. The results of sensitivity and specificity tests suggest that p16 can be used as a surrogate marker for HR-HPV in OSCC and VC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8247-8252
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• 2016

Background: The ubiquitin-proteasome system (UPS) degrades a variety of proteins which attach to specific signals. The ubiquitination pathway facilitates degradation of damaged proteins and regulates growth and stress responses. This pathway is altered in various cancers, including acute lymphoblastic leukemia, head and neck squamous cell carcinoma and breast cancer. Recently it has been reported that expression of newly characterized human genes, UBE2Q1 and UBE2Q2, putative members of ubiquitin-conjugating enzyme family (E2), has been also changed in colorectal cancer. Epigenetics is one of the fastest-growing areas of science and nowadays has become a central issue in biological studies of diseases. According to the lack of information about the role of epigenetic changes on gene expression profiling of UBE2Q1 and UBE2Q2, and the presence of CpG islands in the promoter of these two human genes, we decided to evaluate the promoter methylation status of these genes as a first step. Materials and Methods: The promoter methylation status of UBE2Q1 and UBE2Q2 was studied by methylation-specific PCR (MSP) in tumor samples of 60 colorectal cancer patients compared to adjacent normal tissues and 20 non-malignant controls. The frequency of the methylation for each gene was analyzed by chi-square method. Results: MSP results revealed that UBE2Q2 gene promoter were more unmethylated, while a higher level of methylated allele was observed for UBE2Q1 in tumor tissues compared to the adjacent normal tissues and the non malignant controls. Conclusions: UBE2Q1 and UBE2Q2 genes show different methylation profiles in CRC cases.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5965-5972
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• 2013

PIN1 is one member of the parvulin PPIase family. By controlling Pro-directed phosphorylation, PIN1 plays an important role in cell transformation and oncogenesis. There are many polymorphisms in the PIN1 gene, including rs2233678 and rs2233679 affecting the PIN1 promoter. Recently, a number of case-control studies were conducted to investigate the association between PIN1 gene rs2233678 and rs2233679 polymorphism and cancer risk. However, published data are still conflicting. In this paper, we summarized data for 5,427 cancer cases and 5,469 controls from 9 studies and attempted to assess the susceptibility of PIN1 gene polymorphism to cancers by a synthetic meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. All analyses were performed using Stata software. Our results suggested that rs2233678 represented a protective factor in overall analysis (CC vs GG: OR= 0.697, 95%CI: 0.498-0.976; CG vs GG: OR=0.701, 95%CI: 0.572-0.858; Dominant model: OR= 0.707, 95%CI: 0.590-0.847; C allele vs G allele: OR=0.734, 95%CI: 0.623-0.867) and especially for squamous cell carcinoma of the head and neck, lung cancer and breast cancer in Asians and Caucasians. The rs2233679 polymorphism was significantly associated with decreased cancer risk in overall analysis (CT vs CC: OR=0.893, 95%CI=0.812-0.981; Dominant model: OR=0.893, 95%CI=0.816-0.976; T allele vs C allele; OR=0.947, 95%CI=0.896-1.000) and especially in Asians. In conclusion, our meta-analysis suggested that -842G>C (rs2233678) and -667C>T (rs2233679) may contribute to genetic susceptibility for cancer risks. Further prospective research with larger numbers of worldwide participants is warranted to draw comprehensive and firm conclusions.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.2
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• pp.164-173
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• 2000

The p16 protein is a cyclin dependent kinase inhibitor that inhibits cell cycle progression from $G_1$ phase to S phase in cell cycle. Many p16 gene mutations have been noted in many cancer-cell lines and in some primary cancers, and alterations of p16 gene function by DNA methylation have been noticed in various kinds of cancer tissues and cell-lines. There have been a large body of literature has accumulated indicating that abnormal patterns of DNA methylation (both hypomethylation and hypermethylation) occur in a wide variety of human neoplasma and that these aberrations of DNA methylation may play an important epigenetic role in the development and progression of neoplasia. DNA methylation is a part of the inheritable epigenetic system that influences expression or silencing of genes necessary for normal differentiation and proliferation. Gene activity may be silenced by methylation of up steream regulatory regions. Reactivation is associated with demethylation. Although evidence or a high incidence of p16 alterations in a variety of cell lines and primary tumors has been reported, that has been contested by other investigators. The precise mechanisms by which abnormal methylation might contribute to carcinogenesis are still not fully elucidated, but conceivably could involve the modulation of oncogene and other important regulatory gene expression, in addition to creating areas of genetic instability, thus predisposing to mutational events causing neoplasia. There have been many variable results of studies of head and neck squamous cell carcinoma(HNSCC). This investigation was studied on 13 primary HNSCC for p16 gene status by protein expression in immunohistochemistry, and DNA genetic/epigenetic analyzed to determine the incidence, the mechanisms, and the potential biological significance of its Inactivation. As methylation detection method of p16 gene, the methylation specific PCR(MSP) is sensitive and specific for methylation of any block of CpG sites in a CpG islands using bisulfite-modified DNA. The genomic DNA is modified by treatment with sodium bisulfate, which converts all unmethylated cytosines to uracil(thymidine). The primers designed for MSP were chosen for regions containing frequent cytosines (to distinguish unmodified from modified DNA), and CpG pairs near the 5' end of the primers (to provide maximal discrimination in the PCR between methylated and unmethylated DNA). The two strands of DNA are no longer complementary after bisulfite treatment, primers can be designed for either modified strand. In this study, 13 paraffin embedded block tissues were used, so the fragment of DNA to be amplified was intentionally small, to allow the assessment of methylation pattern in a limited region and to facilitate the application of this technique to samlples. In this 13 primary HNSCC tissues, there was no methylation of p16 promoter gene (detected by MSP and automatic sequencing). The p16 protein-specific immunohistochemical staining was performed on 13 paraffin embedded primary HNSCC tissue samples. Twelve cases among the 13 showed altered expression of p16 proteins (negative expression). In this study, The author suggested that low expression of p16 protein may play an important role in human HNSCC, and this study suggested that many kinds of genetic mechanisms including DNA methylation may play the role in carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2629-2633
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• 2012

Background: Raw betel nut (RBN) chewing is an important contributing factor for esophageal squamous cell carcinoma (ESCC), although associated genomic changes remain unclear. One difficulty in assessing the effects of exclusively RBN induced genetic alterations has been that earlier studies were performed with samples of patients commonly using tobacco and alcohol, in addition to betel-quid. Both CDKN2A (at 9p21) and Rb1 gene (at 13q14.2) are regarded as tumor suppressors involved in the development of ESCC. Therefore, the present study aimed to verify the RBN's ability to induce ESCC and assess the involvement of CDKN2A and Rb1 genes. Methods: A panel of dinucelotide polymorphic markers were chosen for loss of heterozygosity studies in 93 samples of which 34 were collected from patients with only RBN-chewing habit. Promoter hypermethylation was also investigated. Results: Loss in microsatellite markers D9S1748 and D9S1749, located close to exon $1{\beta}$ of CDKN2A/ARF gene at 9p21, was noted in 40% ESCC samples with the habit of RBN-chewing alone. Involvement of a novel site in the 9p23 region was also observed. Promoter hypermethylation of CDKN2A gene in the samples with the habit of only RBN-chewing alone was significantly higher (p=0.01) than Rb1 gene, also from the samples having the habit of use both RBN and tobacco (p=0.047). Conclusions: The data indicate that the disruption of 9p21 where CDKN2A gene resides, is the most frequent critical genetic event in RBN-associated carcinogenesis. The involvement of 9p23 as well as 13q14.2 could be required in later stages in RBN-mediated carcinogenesis.