• 대한화학회지
• /
• 제48권1호
• /
• pp.33-38
• /
• 2004

두경부 편평 세포암종(HNSCC: head and neck squamous cell carcinoma) 의 발생과 관련하여 p53 종양 억제 유전자 (tumor suppressor gene) 의 돌연변이는 높은 비율로 나타나는 것으로 보고 되고 있다. 단국대학교 병원에서 두경부 종양으로 진단 받고 수술 받은 환자의 조직 50개를 대상으로 p53 종양 억제 유전자의 exon 5-8 까지의 영역에서 DNA를 추출하여 PCR-SSCP(polymerase chain reaction single strand conformational polymorphism) 방법과 DHPLC(denaturing high performance liquid chromatography) 방법으로 p53체세포 돌연변이(somatic mutation)를 비교 분석하였다. 그 결과 SSCP 분석 방법은 16개(32%), DHPLC 분석 방법은 17개(34%) 를 검출하였고 그 중 SSCP와 DHPLC 분석 방법 모두 exon 8번에서 결실(deletion) 형태의 돌연변이를 확인하였으며 최종적으로 자동 염기 서열 분석기(automatic DNA sequencer) 를 통하여 모든 돌연변이를 확인하였다. DHPLC 분석방법이 SSCP 방법보다 분석 시간이나 노력이 덜 소모되며 보다 더 정확한 돌연변이 검출 방법임을 확인하였다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제28권1호
• /
• pp.7-15
• /
• 2002

The present study was carried out to evaluate the correlation of metastasis and prognostic factors in squamous cell carcinoma of head and neck. Examination was performed on a series of thirty-seven patients who were confirmed to squamous cell carcinoma and its lymphatic metastasis by pathologist. Correlations of metastasis and other factors such as angiogenesis, histologic grading, and p53 expression and ras oncogene were studied. The depth of tumors was around 1 to 27mm. Twenty cases were more than 10mm deep, of which seventeen cases were shown lymphatic metastasis. Total score of histologic grading including keratinization, nuclear atypia, growth pattern and intensity of inflammation was ranged from 5 to 10 points. Of these factors, nuclear atypia with intensity of inflammation, and nuclear atypia with growth pattern was correlated with nuclear atypia each. For angiogenesis, number of new-formed vessels were counted 13 to 58 each. Twenty-eight cases were shown to lymphatic metastasis. No correlation with histologic grading and lymphatic metastasis was found. The results of immunohistochemical staining for p53 and ras oncogene revealed that positive cases were 16 and 22, negative for 21 and 15 each. However, both were not correlated with histologic grading and lymphatic metastasis. These results were revealed that angiogenesis was not correlated with lymphatic metastasis of squamous cell carcinoma arising in head and neck. Nuclear atypia with intensity of inflammation and dysplasia with growth pattern were correlated with histologic grading, which suggested that more careful and adequate advice is needed for effective treatment.

• 대한기관식도과학회지
• /
• 제7권2호
• /
• pp.152-160
• /
• 2001

The presence of HPV DNA and the expression of p53 protein and proliferating cell nuclear antigen(PCNA) in head and neck squamous cell carcinoma were determined to evaluate the relationship of these factors and their association with their pathologic stages and cervical lymph node metastasis. Among 65 patients the presence of HPV DNA was found in 12 cases(18.5%), p53 was found positive in 32 cases(49.2%) and expression of PCNA was observed in 24 cases(36.9%). The expression of PCNA was more frequent in the HPV positive cancers compared with the HPV negative ones(p =0.0018), and p53 revealed its higher rate of cooccurrence with the expression of PCNA(p =0.008), which might suggest that PCNA expression has a positive relationship with HPV and p53 mutation in head and neck cancer. There might be inverse relationship between HPV and p53 mutation(p =0.063), but 3 cases showed both HPV DNA positivity and p53 expression. HPV was detected at a higher rate in the early pathologic stages than in the advanced stages of cancer, and p53 expression was more frequently found in the advanced stages(p =0.044). These results suggests that HPV and p53 mutation might have different etiologic roles in the development of head and neck cancer, or cases with p53 mutation might have more aggressive behavior. PCNA expression showed no difference between early and late stages of cancer, and between cases with and without cervical lymph node metastasis.

• 대한두경부종양학회지
• /
• 제21권2호
• /
• pp.196-200
• /
• 2005

Objectives: The purpose of this study was to evaluate the incidence and predictive factors of contralateral occult lymph node metastasis in oral cavity squamous cell carcinomas to form a rational basis for elective contralateral neck management. Materials and Methods: We performed a retrospective analysis of 66 N0-2 oral cavity cancer patients undergoing elective neck dissection for contralateral clinically negative necks from 1991 to 2003. Results: Clinically negative but pathologically positive contralateral lymph nodes occurred in 11%(7 of 66) . Of the 11 cases with a clinically ipsilateral node positive neck, contralateral occult lymph node metastases developed in 36%(4 of 10, in contrast with 5%(3/55) in the cases with clinically ipsilateral node negative necks(p<0.05). Based on the clinical staging of the tumor, 8%(3 of 37) of the cases showed lymph node metastases in T2 tumors, 25%(2 of 8) in T3, and 18%(2 of 11) in T4. None of the T1 tumors(10 cases) had pathologically positive lymph nodes. The rate of contralateral occult neck metastasis was significantly higher in advanced stage cases and those crossing the midline, compared to early stage or unilateral lesions(p<0.05). Patients with no evidence of contralateral nodal cancer had significantly improved disease-specific survival over patients with any pathologically positive nodes(5-year disease-specific survival rate was 79% vs. 43%, p<0.05). Conclusion: The risk of contralateral occult neck involvement in the oral cavity squamous cell carcinomas above the T3 stage or those crossing the midline with unilateral metastases was high. Therefore, we advocate an elective contralateral neck treatment with surgery or radiotherapy in oral cavity squamous cell carcinoma patients with ipsilateral node metastases or tumors that are greater than stage T3 or crossing the midline.

• 대한두경부종양학회지
• /
• 제19권1호
• /
• pp.25-33
• /
• 2003

Background and Objectives: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is attenuated virus originally produced as viral vaccines but are also efficient gene transfer vehicle. The main goals of this study were to examine the efficiencies of the gene transfer using DISC vectors for various head and neck squamous cell carcinoma cell lines and to evaluate the efficacy of vaccination with DISC virus carrying a immunomodulatory genes (GM-CSF) as cancer therapy in a organotopic oral cavity squamous cell cancer model. Materials and Methods : We determinated the gene transfer efficiency of DISC virus by x-gal stain method and proved gene and protein expression of DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also we evaluated the ex vivo vaccination effects of SCCVII/GMCSF (DISC-GMCSF transfected SCCVII vaccine) vaccine on preventing the recurrence of micro-residual tumor. After the vaccination of SCCVII/GMCSF, specific cytotoxic T-cell responses was evaluated by CTL assay. Results: At an MOI of 10 DISC virus showed 64-88% of transfection rates in various head and neck squamous cancer cell lines. SCCVII cells transduced by DISC virus vector (MOI=10) carrying the GM-CSF gene, produced 4.5 nanogram quantities of GM-CSF per $10^6$ cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-GMCSF resulted in better protection rate against subsequent tumor recurrence in organotopic oral cavity cancer model. Although tumor free survival rate was not statistically significantly increased in vaccination group (p=0.078), tumor specific cytotocic T-cell responses were significantly increased in SCCVII/GMCSF vaccination group. Conclusion: These data demonstrate that; 1) The DISC virus vector is capable of efficient gene transfer to various head and neck squamous cancer cell lines, 2) GM-CSF secreting genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor recurrence in organotopic micro-residual oral cavity cancer model and produced tumor specific cytotoxic T-cell response. DISC virus-mediated, cytokine gene transfer may prove to be useful as a clinical therapy for head and neck cancers.

• 대한두경부종양학회지
• /
• 제23권1호
• /
• pp.21-25
• /
• 2007

Background：Squamous cell carcinoma(SCC)of the palatine tonsils represents approximately 15-23% of all intraoral SCC. The most frequently reported risk factors for oropharyngeal cancer are smoking and alcohol. In a recent overview of HPV and tonsillar squamous cell carcinoma(TC), 51% contained HPV DNA, and HPV-16 being the most frequent type. We aimed to clarify whether HPV directly effects on the oncogenesis and biologic behavior of TC by comparison with infection prevalence, and physical status of virus. Material and Method：We used HPV genotyping DNA chip(Biocore, Korea, Seoul) arrayed by multiple oligonucleotide probes of L1 sequence of 26 types of HPV and HPV genotypes are identified by fluorescence scanner. The copy numbers of HPV E2 and E6 open reading frames(ORF) were assessed using a TaqMan-based 5'-exonuclease quantitative real-time PCR assay. The ratio of E2 to E6 copy numbers was calculated to determine the physical status of HPV-16 viral gene. Results：We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs(73.1% vs. 11.6%), and most of the HPVs were type 16(87.2%)and non-episomal(94.1%) state. Conclusions：This study regarding HPV infection prevalence and mechanism in the largest population of palatine tonsillar squamous cell carcinoma with chronic follicular tonsillitis revealed significant difference pf HPV prevalence between TC and CFT. Most of HPV were 16 type and integrated or mixed, HPV-16 integration could be directly related to tonsillar carcinogenesis.

• 대한두경부종양학회지
• /
• 제20권2호
• /
• pp.167-171
• /
• 2004

Background and Objectives: Squamous cell carcinoma of retromolar tringone (RMT) is an uncommon head and neck tumor. RMT cancer has unique clinical feature and specific considerations for surgical treatment are needed but, reports on the treatment of RMT cancer are still lacking. Patients and Methods: From May 1997 to July 2004, 8 patients with histologically proven squamous cell carcinoma of the RMT were treated in Severance Hospital. Surgical excision of the primary lesion and neck dissection were performed in all patients. Reconstruction was accomplishing using several methods. Charts and other medical records were reviewed. Results: In early cases, lower cheek flap was appropriate but, mandibular swing or madibulectomy approach was appropriate in advanced cases. Reconstruction was needed in all patients and excision of mandible was needed in majority of patients. 6 patients were disease free status and one died from recurrence and one was lost to follow up. Conclusion: In treatment of RMT cancer, several surgical approach methods and reconstruction should be considered before treatment. Surgical treatment of RMT cancer may be one of a useful primary treatment modality.

• Journal of Oral Medicine and Pain
• /
• 제30권3호
• /
• pp.287-300
• /
• 2005

두경부에서 발생하는 편평세포암종은 같은 조직학적 분류, 조직학적 단계 및 임상 단계에 있다하더라도 항암제 투여에 따른 감수성은 환자마다 다양하게 나타난다. 따라서, 본 연구의 목적은 기존에 가장 많이 사용하는 항암제인 5-FU 와 Cisplatin의 감수성을 예측할 수 있는 생물학적 표지자를 찾아 환자에게 맞는 항암제를 선택하기 위해서이다. 5종의 구강 편평암세포암주를 이용하였으며, 5-FU 와 Cisplatin의 항암제 감수성을 측정하기 위해 MTT assay를 시행하였다. 각 세포 주의 전 RNA를 추출하였으며 이어서 cDNA를 합성하였다. 다양한 유전자를 1) 돌연변이 2) 염증(COX pathway) 3) 세포주기 4) 노화 5) 세포외기질 과 관련되게 분류하였고 RT-PCR을 시행하여 유전자의 발현량을 살펴보았다. 결과물은 Scion image 프로그램을 통해 분석하였고, Sigma plot을 이용해 표시하였다. 5-FU의 감수성과 비례하는 유전자들은 XPA, XPC, OGG, APEX, COX-2, PPAR, Cyclin E, Cyclin B1, CDC2, hTERT, hTR, TIMP-3, TIMP-4 및 HSP47이었으며, Cisplatin의 감수성과 비례하는 유전자들은 COX-1, iNOS, eNOS, PCNA, Col-1 및 MMP-9 으로 알 수 있었다. 위 결과는 암환자에게 알맞은 항암제를 선택 시 항암제의 감수성과 관련한 유전자들의 발현 정도를 파악한다면 올바른 항암제를 선택하는데 도움이 되리라 사료된다.

• 대한기관식도과학회지
• /
• 제8권1호
• /
• pp.35-41
• /
• 2002

Background and Objectives : Angiogenesis within malignant tumors has been considered to be essential for the growth and expansion of cancer cells, especially for solid tumors, and has been implicated in the overall growth and metastases of tumors. Such angiogenesis within tumors depends upon the secretion of vascular growth factor to allow the growth of newly formed vessels from peripheral tissue into the malignant tumor. %n, an exploration of the relations between cancer cells and vascular growth factors is absolutely critical to understanding the growth of malignant tumors. According to recent reports, vascular endothelial growth factor(VEGF) has been found to play a role in lymphatic metastases, tumor recurrence and survival in various human tumors. To evaluate the role of VEGF in head and neck squamous cell carcinoma(HNSCC) we performed this study. Materials and Methods : We examined the expression of VEGF and microvessel density in 39 HNSCC by immunohistochemistry and correlated them with various clinical data such as stage, cervical lymphatic metastasis, recurrence, and overall survival. Results : The expression of VEGF was not correlated with overall stage, T stage and N stage. There was no statistical correlation between the expression of VEGF and recurrence in the Primary site, cervical lymph node, and the distant metastases. There was no statistical correlation between the expression of VEGF and microvessel density. Conclusion : Based on these results, it is suggested that the expression of vascular endothelial growth factor is not a major prognostic factor for head and neck squamous cell carcinoma. Further studies are needed to evaluate significance of VEGF expression in head and neck squamous cell carcinoma.

• 대한두경부종양학회지
• /
• 제13권2호
• /
• pp.228-234
• /
• 1997

Squamous cell carcinoma originating in the parotid gland has rare occurrence. The primary squamous cell carcinoma of the parotid gland comprise about 0.3% and 9.8% of all parotid malignant tumor. We investigated the clinical behavior and treatment outcome of patients with primary squamous cell carcinoma of the parotid gland. We reviewed all cases of possible primary squamous cell carcinoma of the parotid gland treated at Yonsei Cancer Center, Seoul, Korea, from 1981 through 1995. A total of 128 had primary parotid malignancy. Metastatic squamous cell carcinoma and mucoepidermoid carcinoma were excluded in this study. Ten cases of primary squamous cell carcinoma of the parotid gland were identified. 6 cases of them are men & 4 cases are women. The age of patients ranged from 31 to 68 years with median age of 55 years. On physical examination, 5 cases had palpated cervical neck node and 6 cases had facial nerve palsy. Staging was done according to the current guidelines established by the American Joint Committee on Cancer (1992). Two cases were stage I, 1 in stage III, and 7 in stage IV. Six cases were performed operation and postoperative radiation therapy. Four cases were treated by curative radiation therapy, dose of more than 65 Gy on parotid gland region. The 5 year actual survival rate and the 5 year disease free survival rate were 30.8%, and 40.0%. Initial complete response rate was 70% for all patients. Local failure were occurred 3 of 7 patients with local controlled cases, failure sites were primary site, ipsilateral cervical neck node, contralateral supraclavicular node. Most recurrences developed within 1 year of initial treatment. Distant metastasis was appeared 2 of 3 patients who did not achieved local control. Primary squamous cell carcinoma of the parotid gland occured infrequently. A retrospective study at the Yonsei Cancer Center indicates incidence of 7.8%. At diagnosis, advanced stage, neck node presentation, facial nerve paralysis were associated with a poor prognosis. These results may suggested that radical surgical excision may be treatment of choice and that planned postoperative radiotherapy may be bendicial for reducing locoregional recurrence rates.