Detection of MAGE and SSX Gene Expressions by RT-nested PCR Using Common Primers in Head and Neck Cancer

송달원,김동은,신승진,정승곤,이강대 대한이비인후과학회 2008 Clinical and Experimental Otorhinolaryngology Vol.1 No.2

Objectives. The melanoma antigen gene (MAGE) and synovial sarcoma on X chromosome (SSX) gene families are silent in most normal adult tissues, but are expressed in a variety of malignant lesions. Therefore, detection of MAGE and SSX transcription may be useful for the diagnosis of head and neck cancers. The aim of this study is to detect MAGE and SSX gene transcripts of head and neck cancers using the MAGE 1-6 assay and the SSX 1-9 assay. Methods. The transcripts of MAGE 1-6 and SSX 1-9 genes were detected by the MAGE 1-6 assay and the SSX 1-9 assay respectively, in cancer cell lines, cancer tissue, and induced sputum specimens from head and neck cancer patients. Results. The transcripts of MAGE 1-6 and SSX 1-9 genes were detected in 82.8% and 75.9% of head and neck cancer tissues (N=29) respectively, and 96.6% of cancer tissues expressed at least one of MAGE 1-6 or SSX 1-9 genes. In the induced sputum of head and neck cancer patients (N=18), the transcripts of MAGE 1-6 and SSX 1-9 genes were detected in 72.2% and 77.8%, respectively, and 94.4% of the sputum specimens were positive for either the MAGE 1-6 or the SSX 1-9 assay. Conclusion. These results suggest that the combination of MAGE 1-6 and SSX 1-9 assays may be useful in the diagnosis of head and neck cancer. Objectives. The melanoma antigen gene (MAGE) and synovial sarcoma on X chromosome (SSX) gene families are silent in most normal adult tissues, but are expressed in a variety of malignant lesions. Therefore, detection of MAGE and SSX transcription may be useful for the diagnosis of head and neck cancers. The aim of this study is to detect MAGE and SSX gene transcripts of head and neck cancers using the MAGE 1-6 assay and the SSX 1-9 assay. Methods. The transcripts of MAGE 1-6 and SSX 1-9 genes were detected by the MAGE 1-6 assay and the SSX 1-9 assay respectively, in cancer cell lines, cancer tissue, and induced sputum specimens from head and neck cancer patients. Results. The transcripts of MAGE 1-6 and SSX 1-9 genes were detected in 82.8% and 75.9% of head and neck cancer tissues (N=29) respectively, and 96.6% of cancer tissues expressed at least one of MAGE 1-6 or SSX 1-9 genes. In the induced sputum of head and neck cancer patients (N=18), the transcripts of MAGE 1-6 and SSX 1-9 genes were detected in 72.2% and 77.8%, respectively, and 94.4% of the sputum specimens were positive for either the MAGE 1-6 or the SSX 1-9 assay. Conclusion. These results suggest that the combination of MAGE 1-6 and SSX 1-9 assays may be useful in the diagnosis of head and neck cancer.

Effect of Metformin on Progression of Head and Neck Cancers, Occurrence of Second Primary Cancers, and Cause-Specific Survival

Kwon, Minsu,Roh, Jong-Lyel,Song, Jihyun,Lee, Sang-Wook,Kim, Sung-Bae,Choi, Seung-Ho,Nam, Soon Yuhl AlphaMed Press 2015 The oncologist Vol.20 No.5

<P>This study aimed to investigate the effect of metformin on progression of head and neck cancers (HNC), occurrence of second primary cancers, and cause-specific survival. Results showed that metformin did not significantly affect the clinical course of patients with HNC but suggested that diabetes had a crucial impact on the clinical course of patients with HNC who were not overcome by metformin use.</P><P><B>Background.</B></P><P>This study aimed to investigate the effect of metformin on progression of head and neck cancers, occurrence of second primary cancers, and cause-specific survival.</P><P><B>Methods.</B></P><P>This study analyzed a retrospective cohort of 1,151 consecutive patients with head and neck squamous cell carcinoma who were treated at our hospital. Patients were divided into three groups: nondiabetic, nonmetformin, and metformin. Clinical characteristics, recurrence of index head and neck cancer, occurrence of second primary cancer, and survival were compared among the different groups.</P><P><B>Results.</B></P><P>Of 1,151 patients, 99 (8.6%) were included in the metformin group, 79 (6.8%) were in the nonmetformin group, and 973 (84.5%) were in the nondiabetic group. Diabetic status and metformin exposure had no significant impact on index head and neck cancer recurrence or second primary cancer development (<I>p</I> > .2). The nonmetformin group showed relatively lower overall (<I>p</I> = .017) and cancer-specific (<I>p</I> = .054) survival rates than the other groups in univariate analyses, but these results were not confirmed in multivariate analyses.</P><P><B>Conclusion.</B></P><P>Metformin use did not show beneficial effects on index tumor progression, second primary cancer occurrence, and cause-specific survival in patients with head and neck cancer compared with nonmetformin users and nondiabetic patients.</P>

두경부암 림프절 전이 평가에서 PET-MRI의 임상적 유용성

김정수,이홍재,김진의,Kim, Jung-Soo,Lee, Hong-Jae,Kim, Jin-Eui 대한핵의학기술학회 2014 핵의학 기술 Vol.18 No.1

Purpose: As PET-MRI which has excellent soft tissue contrast is developed as integration system, many researches about clinical application are being conducted by comparing with existing display equipments. Because PET-MRI is actively used for head and neck cancer diagnosis in our hospital, lymph node metastasis before the patient's surgery was diagnosed and clinical usefulness of head and neck cancer PET-MRI scan was evaluated using pathological opinions and idiopathy surrounding tissue metastasis evaluation method. Materials and Methods: Targeting 100 head and neck cancer patients in SNUH from January to August in 2013. $^{18}F-FDG$ (5.18 MBq/kg) was intravenous injected and after 60 min of rest, torso (body TIM coil, Vibe-Dixon) and dedication (head-neck TIM coil, UTE, Dotarem injection) scans were conducted using $Bio-graph^{TM}$ mMR 3T (SIEMENS, Munich). Data were reorganized using iterative reconstruction and lymph node metastasis was read with Syngo.Via workstation. Subsequently, pathological observations and diagnosis before-and-after surgery were examined with integrated medical information system (EMR, best-care) in SNUH. Patient's diagnostic information was entered in each category of $2{\times}2$ decision matrix and was classified into true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Based on these classified test results, sensitivity, specificity, accuracy, false negative and false positive rate were calculated. Results: In PET-MRI scan results of head and neck cancer patients, positive and negative cases of lymph node metastasis were 49 and 51 cases respectively and positive and negative lymph node metastasis through before-and-after surgery pathological results were 46 and 54 cases respectively. In both tests, TP which received positive lymph node metastasis were analyzed as 34 cases, FP which received positive lymph node metastasis in PET-MRI scan but received negative lymph node metastasis in pathological test were 4 cases, FN which received negative lymph node metastasis but received positive lymph node metastasis in pathological test was 1 case, and TN which received negative lymph node metastasis in both two tests were 50 cases. Based on these data, sensitivity in PET-MRI scan of head and neck cancer patient was identified to be 97.8%, specificity was 92.5%, accuracy was 95%, FN rate was 2.1% and FP rate was 7.00% respectively. Conclusion: PET-MRI which can apply the acquired functional information using high tissue contrast and various sequences was considered to be useful in determining the weapons before-and-after surgery in head and neck cancer diagnosis or in the evaluation of recurrence and remote detection of metastasis and uncertain idiopathy cervical lymph node metastasis. Additionally, clinical usefulness of PET-MRI through pathological test and integrated diagnosis and follow-up scan was considered to be sufficient as a standard diagnosis scan of head and neck cancer, and additional researches about the development of optimum MR sequence and clinical application are required. 수술 전 림프절 전이 여부를 진단하고 병리학적 소견 및 원발 주위조직 전이 평가법을 이용하여 두경부암 PET-MRI 검사의 임상적 유용성을 평가하였다. 두경부암 환자 100명을 대상으로 $^{18}F-FDG$ (5.18 MBq/kg)를 정맥주사하고 60분 안정을 취한 후, BiographTM mMR 3T를 사용하여 torso(body tim coil, Vibe-Dixon)와 dedication (head/neck tim coil, UTE, Dotarem injection) 검사를 시행하였다. 반복계산법을 적용하여 데이터를 재구성한 후 workstation으로 림프절 전이 여부를 판독하고, 본원 종합의료정보시스템으로 수술 전/후 병리학적 검사 소견을 조사하였다. 환자의 진단 정보를 $2{\times}2$ 판정행렬의 각 항목에 기입하여 진양성, 진음성, 위양성, 위음성으로 구분하고 이렇게 구분된 검사결과를 토대로 예민도, 특이도, 정확도, 위음성률, 위양성률을 산출하였다. 두경부암 환자의 PET-MRI 검사 결과에서 림프절 전이 양성 및 음성 판정을 받은 경우는 각 49건, 51건이었으며 수술 전-후 병리학적 결과를 통해 림프절 전이 양성 및 음성 판정을 받은 경우는 각 46건, 54건으로 나타났다. 이 중 두 검사 모두 림프절 전이 양성 판정을 받은 진양성은 45건, PET-MRI 검사에서는 림프절 전이 양성이지만 병리학적 검사에서 림프절 전이 음성 판정을 받은 위양성은 4건, PET-MRI 검사에서 림프절 전이 음성이지만 병리학적 검사에서 양성 판정을 받은 위음성은 1건, 두 검사 모두 림프절 전이 음성 판정을 받은 진음성은 50건으로 분석되었다. 따라서 두경부암 환자의 PET-MRI 검사의 예민도는 97.8%, 특이도는 92.5%, 정확도는 95%, 위음성률은 2.1%, 위양성률은 7.0%로 나타났다. 따라서 PET-MRI는 두경부암의 진단에 있어 수술 전 병기 결정이나 치료 후 재발 및 원격전이의 발견, 불분명한 원발 경부 림프절 전이 등의 평가에 유용할 것으로 판단된다.

두경부암 환자에서 루골용액을 이용한 식도 내시경 선별검사

하남욱,이강대,이형신,홍종철,이환호,박선자 대한이비인후과학회 2006 대한이비인후과학회지 두경부외과학 Vol.49 No.10

Background and Objectives:Second primary esophageal cancer has been reported to comprise 6-9% of head and neckcancer cases, which are frequently detected in the advanced stage. Thus, detecting esophageal cancer in the early stage is importantin the prognosis of head and neck cancer. However, it is difficult to detect early lesions using the conventional endoscopy.In the current study, the feasibility of endoscopic screening using Lugols solution was assessing for detecting early esophagealcancer in patients of head and neck cancer. Subjects and Method:Sixty-two patients (Group I-synchronous cancer studygroup) diagnosed with head and neck cancer between November, 2003 and November, 2004 were prospectively studied. Fortysixpatients (Group II-metachronous cancer study group) under the follow-up care with head and neck cancer during the sameperiod were also evaluated. The esophagus was initially observed under direct endoscopic view and then Lugol dye was sprayedat the esophagus. Any unstained area was biopsied. Results:Of 34 patients (54.8%) with unstained lesions in Group I, 10(16.1%) showed dysplasia and 4 (6.4%) had cancer. Of 21 patients (45.6%) with unstained lesions in Group II, 2 (4.3%)showed dysplasia and 5 (10.8%) had cancer. Among 9 (8.3%) second primary esophageal cancer, 6 were detected with superficialesophageal cancer while the other 3 were found to be in the advanced stage of cancer. This superficial cancer revealed nonspecificmucosal findings in the direct endoscopic view and was difficult to be visualized as a pathologic lesion; however, itrevealed unstained areas when Lugol’s solution was sprayed, thus could be diagnosed as cancer through biopsy of the area.Conclusion:Endoscopy of esophagus with Lugol’s solution could be highly effective as a screening method to detect secondprimary esophageal cancer in patients with head and neck cancer. (Korean J Otolaryngol 2006;49:1008-13)

두경부 종양세포주에 대한 Mithramycin A의 세포자멸사 유도성 및Cisplatin 항암작용 증가효과

이강대,손성환,박종욱,김영록,이봉주,김주연 고신대학교의과대학 2008 고신대학교 의과대학 학술지 Vol.23 No.1

Background and Objectives : Cisplatin (CP) is a major chemotherapeutic agent for head and neck cancer. However, cancer cells can get drug resistance through recovering the DNA damage by CP. Mithramycin A (MA) can inhibit gene expression of multidrug resistance gene 1, c-myc or h-ras. The goal of this study is to evaluate the therapeutic effect of MA alone and combination of MA and CP on head and neck cancer cell lines. Materials and Methods : Two head and neck cancer cell lines (AMC-HN4, AMC-HN7) were treated with MA. The cellular proliferation, apoptosis and protein expression were measured with XTT assay, FACS analysis, and western blotting, respectively after MA treatment in cell lines. In order to know the combination effect of MA with CP, the cancer cell lines were treated with MA, CP, and MA/CP combination, and cellular proliferation, apoptosis and expression of apoptosis-associated proteins were measured. Results : MA inhibited the proliferation of head and neck cancer cells and induce dapoptosis. Increase of caspase activation, PLC-?1 fragmentation and percent apoptosis by MA treatment was blocked by z-VAD-fms, but not blocked by N-Acetyl Cystein. Combination of MA and CP significantly inhibited cancer cell growth and increased apoptosis compared to MA and CP alone, and it also suppressed the expression of anti-apoptotic proteins such as XIAP and Mcl-1. Conclusions : The present study suggests that MA alone andMA/CP combination chemotherapy could be a potential regiment for the control of the head and neck cancer.

Stage-Wise Presentation of Non-Metastatic Head and Neck Cancer: an Analysis of Patients from the Kumaon Hills of India

Pandey, Kailash Chandra,Revannasiddaiah, Swaroop,Pant, Nirdosh Kumar,Bhatt, Harish Chandra Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: Head and neck cancer without distant metastases is amenable to various modalities of treatment. However, the stage at presentation is a very important determinant for treatment success. The present study was conducted to determine the stage-wise presentation of non-metastatic head and neck cancer patients from the hilly regions in Kumaon division of Uttarakhand, India. Materials and Methods: The hospital records for non-metastatic head and neck cancer patients from the only functional cancer centre of the region for the period of two-years (January 2012-December 2013) were included. Nasopharyngeal carcinoma was excluded due to its staging system being different. Non-squamous histopathologies were also excluded. Patients hailing from nearby regions of Uttar Pradesh and Nepal were excluded, as were patients from non-hilly regions of Kumaon. Results: Of the 271 patients of head and neck cancer, 27 with distant metastases at diagnosis were excluded from the analysis. Of the 244 eligible patient records, 90.1% (n=222) were male, and 9.9% (n=22) were female. The proportions of patients with carcinoma of the larynx, oropharynx, oral cavity, hypopharynx and maxillary antrum were 31.9% (n=78), 27.9% (n=68), 20.5% (n=50), 12.7% (n=31) and 1.2% (n=3). A further 5.7% (n=14) were diagnosed as having secondary involvement of neck nodes with unknown primaries. The proportion of patients presenting in stages I, II, III, IVA and IVB were 0.8% (n=2), 2.5% (n=6), 9.4% (n=23), 51.6% (n=126) and 35.7% (n=87) respectively. Conclusions: An abysmally low proportion (3.3%) of non-metastatic head and neck cancer patients presented in the early stages (I and II). A vast majority of the patients (88.1%) presented with stages IVA and IVB. Not only does this reflect a poor therapeutic outlook, but also exposes the dire need for programmes focusing on cancer awareness and early detection in the region.

두경부종양환자에서 시행한 상부위장관검사의 유용성

장지영(Ji Young Jang),조문준(Moon June Cho),김준상(Jun Sang Kim),김병국(Byoung Kook Kim),정현용(Hyun Yong Jeong),김재성(Jae Sung Kim) 대한두경부종양학회 1999 대한두경부 종양학회지 Vol.15 No.2

Background and Objectives: Multiple primary tumors of the upper aerodigestive tract are not unusual. We examined head and neck cancer patients to discover the presence of second primary cancer in their upper gastrointestinal tract, using esophagogastroscopy. Materials and Methods: Endoscopic examination of the upper gastrointestinal tract was performed on 51 patients whose head and neck cancers were treated at department of therapeutic radiology from August 1996 to April 1999. Two of all patients had been studied by barium swallowing study. In 51 patients, twenty-four had a primary tumor in the larynx, 8 in the oropharynx, 6 in the nasopharynx, 6 in the oral cavity, 6 in the hypopharynx, and 1 in the nasal cavity. Endoscopically pathologic lesions were biopsied. In control group, endoscopy was performed on 1097 patients who didn't complain any symptoms. Results: Endoscopy showed early malignant lesions in 4 cases(7.7%). Histology of esophageal cancers showed squamous cell carcinoma. Malignant lesions of stomach in 2 cases were histologically identified as adenocarcinoma. Two esophageal cancers occurred in patients whose primary lesions had oropharynx and hypopharynx. Two cases of gastric cancer were also accompanied by oropharynx and hypopharynx. The incidence of second primary cancer was 2 in oropharynx and 2 in hypopharynx. In all cases, second primary cancers were found simultaneously. In control group, 9(0.8%) of 1097 patients were confirmed as early esophageal and gastric cancers. Conclusion: The majority of esophageal and gastric cancer detected by endoscopy were early stage in both head and neck cancer and control group. The incidence of esophageal and gastric cancer of head and neck cancer patients was 10 times as high as that of control group. Although followup period was short, all second primary cancers were detected simultaneously. We would recommend that endoscopic evaluation be included in the workup and followup of all patients with newly diagnosed head and neck cancer.

Clinicopathological Profile of Head and Neck Cancers in the Western Development Region, Nepal: A 4-Year Snapshot

Lasrado, Savita,Prabhu, Prashanth,Kakria, Anjali,Kanchan, Tanuj,Pant, Sadip,Sathian, Brijesh,Gangadharan, P.,Binu, V.S.,Arathisenthil, S.V.,Jeergal, Prabhakar A.,Luis, Neil A.,Menezes, Ritesh G. Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Regional cancer epidemiology is an important basis for determining the priorities for cancer control in different countries worldwide. There is no reliable information about the pattern of head and neck cancer in western Nepal and hence an attempt was here made to evaluate the situation based on hospital data, which provide the only source in the western region of Nepal. A clinicopathological analysis of head and neck cancers treated between 2003 and 2006 in Manipal Teaching Hospital affiliated to Manipal College of Medical Sciences, Pokhara, Western Development Region, Nepal was performed. A total of 105 head and neck cancer cases were identified with a male to female ratio of 1.8:1. The median ages of male and female patients were 62 and 64 years, respectively. Ninety-seven (92.4%) of the cancer patients were suffering from carcinoma, three (2.9%) had blastoma, three (2.9%) had sarcoma, and two (1.9%) had lymphoma. The majority (61.9%) of carcinoma cases were squamous cell carcinoma followed by anaplastic carcinoma (7.2%). Of the carcinoma cases, the most common site of primary lesion was larynx (19.6%), followed by the thyroid (14.4%), the tongue and hypopharynx with 10.3% cases each. Comparative analysis among males and females did not reveal any sex difference in type of head and neck cancers. The head and neck cancer pattern revealed by the present study provides valuable leads to cancer epidemiology in western Nepal and useful information for health planning and cancer control, and future research in western Nepal.

Role of Concomitant Chemoradiation in Locally Advanced Head and Neck Cancers

Lasrado, Savita,Moras, Kuldeep,Pinto, George Jawahar Oliver,Bhat, Mahesh,Hegde, Sanath,Sathian, Brijesh,Luis, Neil Aaron Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.10

Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.

Genetic Deletions of GSTM1 and GSTT1 in Head and Neck Cancer: Review of the Literature from 2000 to 2012

Masood, Nosheen,Yasmin, Azra,Kayani, Mahmood A. Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

Head and neck cancer is one of the leading causes of deaths worldwide. Two genes GSTM1 and GSTT1 involved in phase II of carcinogen detoxification have been frequently studied in the literature. Their null genotypes are thought to be associated with increased head and neck cancer risk. However, the published reviews are not up to date and many important papers have been skipped. The current literature review was restricted to the null genotypes of the GSTM1 and GSTT1 genes with special emphasis on the genotypic status. We found that the size of study sample varied greatly and the oral cavity cancer was more influenced by GSTM1 and GSTT1 gene deletions. With respect to ethnicity Asians are more prone to head and neck cancers with these null genotypes as compared to Europeans and Americans. The current review showed significant associations (OR=9.0, 95%CI; 1.4-9.5; OR=3.7, 95%CI; 1.4-9.5) of GSTM1 and GSTT1 null genotypes with head and neck cancers. Review confirms the data of previous reviews that GSTM1 and GSTT1 gene polymorphisms may be risk factors for cancer initiation.