Pakpoom Supiyaphun

Genomic alterations in nasopharyngeal carcinoma: loss of heterozygosity and Epstein-Barr virus infection

Nasopharyngeal carcinoma is a subset of head and neck squamous cell cancers with unique endemic distribution and aetiological co-factors. Epstein-Barr virus has been revealed to be an important aetiological factor for most nasopharyngeal carcinomas. Nevertheless, additional genetic alterations may be involved in their development and progression. The aim of this study was to determine the likely chromosomal locations of tumour-suppressor genes related to Epstein-Barr virus-associated nasopharyngeal carcinoma. Fifty-six microsatellite polymorphic markers located on every autosomal arm were used to estimate the incidence of loss of heterozygosity in 27 Epstein-Barr virus-associated nasopharyngeal carcinomas. High frequencies of allelic loss were observed on chromosome 3p (75.0%) and 9p (87.0%). Chromosome 9q, 11q, 13q and 14q displayed loss in over 50%, while chromosome 3q, 6p, 16q, 19q and 22q exhibited loss in 35-50%. Furthermore, several other chromosomal arms demonstrated allelic loss in 20-35%. Additionally, 1 of the 27 cases showed microsatellite instability at multiple loci. These findings provide evidence of multiple genetic alterations during cancer development and clues for further studies of tumour-suppressor genes in Epstein-Barr virus-associated nasopharyngeal carcinoma.

Global Gene Expression Profile of Nasopharyngeal Carcinoma by Laser Capture Microdissection and Complementary DNA Microarrays

A number of genetic and epigenetic changes underlying the development of nasopharyngeal carcinomas have recently been identified. However, there is still limited information on the nature of the genes and gene products whose aberrant expression and activity promote the malignant conversion of nasopharyngeal epithelium. Here, we have performed a genome-wide transcriptome analysis by probing cDNA microarrays with fluorescent-labeled amplified RNA derived from laser capture microdissected cells procured from normal nasopharyngeal epithelium and areas of metaplasia-dysplasia and carcinoma from EBV-associated nasopharyngeal carcinomas. This approach enabled the identification of genes differentially expressed in each cell population, as well as numerous genes whose expression can help explain the aggressive clinical nature of this tumor type. For example, genes indicating cell cycle aberrations (cyclin D2, cyclin B1, activator of S-phase kinase, and the cell cycle checkpoint kinase, CHK1) and invasive-metastatic potential (matrix metalloproteinase 11, v-Ral, and integrin β4) were highly expressed in tumor cells. In contrast, genes underexpressed in tumors included genes involved in apoptosis (B-cell CLL/lymphoma 6, secretory leukocyte protease inhibitor, and calpastatin), cell structure (keratin 7 and carcinoembryonic antigen-related cell adhesion molecule 6), and putative tumor suppressor genes (H-Ras-like suppressor 3, retinoic acid receptor responder 1, and growth arrested specific 8) among others. Gene expression patterns also suggested alterations in the Wnt/β-catenin and transforming growth factor β pathways in nasopharyngeal carcinoma. Thus, expression profiles indicate that aberrant expression of growth, survival, and invasion-promoting genes may contribute to the molecular pathogenesis of nasopharyngeal carcinoma. Ultimately, this approach may facilitate the identification of clinical useful markers of disease progression and novel potential therapeutic targets for nasopharyngeal carcinoma.

Loss of heterozygosity on chromosome 14 in nasopharyngeal carcinoma.

The main objective of this study was to determine the precise frequency of chromosome 14q loss of heterozygosity in nasopharyngeal carcinomas and to define its minimal deletion regions. Thirty‐nine tumors were selected for PCR‐based deletion mapping using 19 microsatellite polymorphic markers spanning the long arm of this chromosome. Loss of heterozygosity for at least one marker was observed in 29 (74.4%) tumors, while 24 of these tumors displayed partial loss and provided an informative basis for detailed deletion mapping. Three minimal regions of loss were delineated, the first defined by markers D14S278 and D14S288, the second being between D14S51 and the telomere. These data confirmed 2 potential tumor‐suppressor‐gene loci at 14q12‐13 and 14 q32. Interestingly, the third region of loss was located at the T‐cell‐receptor delta‐chain locus. This may reflect another tumor‐suppressor‐gene locus at 14q11.2, or may be the consequence of a specific genomic rearrangement of this region. In addition, these allelic losses occurred with high frequency in all tumor grades and stages and in all histological sub‐types. These findings suggest that the genetic alteration of chromosome 14 is common and crucial during nasopharyngeal‐carcinoma development. Int. J. Cancer 78:153–156, 1998.© 1998 Wiley‐Liss, Inc.

Cytochrome P450 2E1 polymorphism and nasopharyngeal carcinoma development in Thailand: a correlative study

BackgroundNasopharyngeal carcinoma (NPC) is a rare tumor in most parts of the world but occurs at relatively high frequency among people of Chinese descent. The cytochrome P450 2E1 enzyme (CYP2E1) is responsible for the metabolic activation of nitrosamines, and has been shown to be a susceptibility gene for NPC development in Taiwan [RR = 2.6; 95%CI = 1.2-5.7]. Since there has been only one report of this link, it was decided to investigate the susceptibility of CYP2E1 to NPC development in other populations. Therefore, the correlation between the RsaI polymorphism of this gene and NPC was studied in-patients including Thai and Chinese in Thailand. The present study comprised 217 cases diagnosed with NPC and 297 healthy controls.ResultsSimilar to the result found in Taiwanese, a homozygous uncut genotype demonstrated a higher relative risk both when all cases were analyzed [RR = 2.19; 95%CI = 0.62-8.68] or individual racial groups, Thai [RR = 1.51; 95%CI = 0.08-90.06] or Chinese [RR = 1.99; 95%CI = 0.39-10.87]. The ethnicity-adjusted odds ratio is 2.39 with 95%CI, 0.72-7.89.ConclusionsThough our finding was not statistically significant due to the moderate sample size of the study, similarity to the study in Taiwan with only a slight loss in precision was demonstrated. The higher RR found for the same genotype in distinct populations confirmed that CYP2E1 is one of several NPC susceptibility genes and that the RsaI minus variant is one mutation that affects phenotype.

Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer

BackgroundEpstein-Barr virus (EBV) associated nasopharyngeal cancer (NPC) is an important squamous cell cancer endemic in Southeast Asia and the Far East and can be considered a multifactorial genetic disease. This research explores potential associations between nasopharyngeal epithelial EBV receptor and NPC susceptibility. To prove the hypothesis, we evaluated two candidate genes, complement receptor 2 (CR2) and polymeric immunoglobulin receptor (PIGR) by using 4 SNPs, CR2 IVS2-848C→T, PIGR IVS3-156G→T, PIGR 1093G→A and PIGR 1739C→T, to genotype 175 cases and 317 controls, divided into Thai, Chinese and Thai-Chinese based on their respective ethnic origins.ResultsThe results obtained indicated that PIGR is an NPC susceptibility gene. The risk association pertaining to each ethnic group was detected for homozygous PIGR 1739C with a significant ethnic group adjusted OR (95%CI) of 2.71(1.72–4.23) and p < 0.00001. Haplotype of the two missense PIGR SNPs, 1093G→A and 1739C→T, and sequence analyses have confirmed the role of the nucleotide PIGR 1739 and excluded possibility of an additional significant nonsynonymous NPC susceptibility SNP.ConclusionsWe present genetic evidence leading to hypothesize a possibility of PIGR to function as the EBV nasopharyngeal epithelium receptor via IgA-EBV complex transcytosis failure. The PIGR 1739C→T is a missense mutation changing alanine to valine near endoproteolytic cleavage site. This variant could alter the efficiency of PIGR to release IgA-EBV complex and consequently increase the susceptibility of populations in endemic areas to develop NPC.

KTP laser inferior turbinoplasty: an alternative procedure to treat the nasal obstruction

OBJECTIVE Nasal obstruction resulting from inferior turbinate hypertrophy (ITH) was treated with KTP laser inferior turbinoplasty (KIT). The effectiveness of the procedure was assessed. METHODS A prospective clinical trial was carried out in King Chulalongkorn Memorial Hospital from October 1, 1998 to September 30, 2000. Forty-eight patients with chronic nasal obstruction underwent KIT. Nasal obstruction was pre- and postoperatively assessed, based on 4-point scale, by the patient and investigator. The scores were compared by paired t-test. The correlation of assessment by the patient and investigator was also demonstrated by weighted kappa test. Pre- and postoperative rhinomanometric evaluations were performed in 29 patients and were compared with paired t-test. RESULTS Significant reduction of nasal obstruction was obtained from assessment by the patient (P<0.000) and by the investigator (P<0.000). The symptoms of sneezing, itching and rhinorrhea were significantly reduced postoperatively (P<0.000). The cure and improvement rate of nasal obstruction were at 70.8 and 100% (assessed by the patient) and at 77.1 and 100% (assessed by the investigator) respectively, and they showed a moderate correlation (Kw=0.65). Rhinomanometrically, the total airway resistance decreased but of not statistic significance (P=0.219), however, the inspired nasal airflow at 150 Pa and the volume of nasal cavities were significantly increased (P<0.00 and P<0.001, respectively). CONCLUSION KIP was shown to effectively reduce the symptom and sign of nasal obstruction as well as other nasal symptoms without any significant complications. It should be an alternative method in treating the patients with nasal obstruction resulting from hyperplastic inferior turbinate.

Identification of distinct regions of allelic loss on chromosome 13q in nasopharyngeal cancer from paraffin embedded tissues

Our main purpose was to identify tumor suppressor gene loci on chromosome 13 responsible for nasopharyngeal cancer (NPC) development by analyzing loss of heterozygosity (LOH) and RB protein expression in paraffin embedded tissues. Normal and tumor DNA were extracted from microdissected samples, and their whole genomes were amplified using degenerate oligonucleotide primers. The polymerase chain reaction (PCR) products were analyzed by repeated amplification using primers derived from 16 microsatellite regions spanning the long arm of this chromosome. Among 50 informative cases, LOH was observed in 44 tumors. Thirty‐one tumors displayed partial loss and provided an informative basis for detailed deletion mapping. Three minimal regions of loss were delineated; the first flanked by D13S120 and D13S219, the second by D13S126 and D13S119, and the third by D13S137 and 13qter. These 3 regions were linked to BRCA2 on 13q12, RB1 on 13q14, and 13q14.3‐ter, respectively. Seven and 4 cases showed LOH either on 13q12 or 13q14, respectively. Nineteen cases showed LOH of both loci separately. One NPC displayed 13q12 and 13q14.3‐ter LOH. RB protein expression was detectable in 76% of the cases. Ten out of 15 cases with the allelic losses limited to 13q14 showed RB protein expression. Contrasting that, 6 out of 7 cases devoid of RB protein expressions showed 13q14LOH. In conclusion, 13qLOH, involving 3 tumor suppressor gene loci, appears to be a frequent genetic event occurring during NPC development. However, other tumor suppressor genes besides RB1, may be responsible for the majority of 13q14LOH. Int. J. Cancer 83:210–214, 1999.

A case of aural gnathostomiasis.

A young Thai woman was afflicted with aural gnathostomiasis. The only symptom she had was sudden intermittent otalgia without apparent hearing loss, tinnitus, vertigo or otorrhea. Presumptive diagnosis was made from the recent history of ingesting raw fish with subsequent migratory swellings. Definite diagnosis rested on identification of the worms, pertinent eosinophilia and positive skin test. This case was different from those previously reported because it was a primary aural gnathostomiasis without neurological involvement.

Solitary schwannoma of the tympanic membrane: a case report

The external ear canal may be occluded by a rare tumor of the tympanic membrane. We reported herein a case of solid schwannoma arising from the tympanic membrane of a 29-year-old man. It presented as a circumscribed and encapsulated tumor of the external ear canal. The definite diagnosis was based on a careful microscopic examination and pathological findings. A precise excision of the tumor together with part of the tympanic membrane, followed by a myringoplasty was performed. To the best of our knowledge, our case should be the first reported case of this entity in the world literature.

Auricular pseudocysts: A treatment with the Chulalongkorn University vacuum device

Auricular pseudocysts are rare lesions that present as an asymptomatic cystic swelling of the anterior surface of the auricle, particularly the antihelix. Typically, the pseudocysts contain viscous straw-yellow fluid similar in appearance to olive oil; however, a clear pale yellow serous transudate may also be encountered. Various therapeutic approaches have been used with variable success. We describe a simple small vacuum device called the Chulalongkorn University vacuum device, which was developed in our center. The device can be easily made anywhere by any surgeon. We report the outcome in 17 patients treated by means of needle aspiration plus application of the Chulalongkorn University vacuum device for 5 days. A complete resolution of the lesion was obtained in 15 (88.2%) patients. Because the procedure is safe and effective and does not require an operating room setting, it may be accepted as an option in the treatment of auricular pseudocysts.