Sheen Yie Fang

A 2·6 Mb interval on chromosome 6q25.2–q25.3 is commonly deleted in human nasal natural killer/T-cell lymphoma

Summary. Natural killer (NK)/T‐cell lymphoma is a special subtype of rare malignant lymphoma that is more prevalent in Asia than in America and Europe. This newly characterized haemato‐lymphoid malignancy is highly aggressive and frequently present in nasal and upper aerodigestive sites. Several studies have reported the commonly deleted region of chromosome 6q21–25 in this particular type of lymphoma. To refine the smallest region of overlapping (SRO) deletion for localization of potential tumour suppressor (TS) genes, we performed loss of heterozygosity (LOH) and homozygosity mapping of deletion (HOMOD) analyses on 37 nasal and nasal‐type NK/T‐cell lymphoma patients using a panel of 25 microsatellite markers, covering the 6q21–q25 region. In all patients studied, LOH was detected in eight (89%) paired‐sample patients, while hemizygous deletion was detected in three (11%) single‐sample patients. Combination of the LOH and HOMOD results defined a distinct 3 Mb SRO on chromosome 6q25. Quantitative multiplex polymerase chain reaction analysis of 10 sequence‐tagged sites further refined the putative TS‐gene‐containing region to a 2·6 Mb interval between TIAM2 and SNX9. Eighteen known genes/Unigene clusters and 25 hypothetical genes are located within this 2·6 Mb region, but none are previously identified TS genes. These results provide a framework for future positional cloning of novel TS gene(s) at 6q25.2–q25.3.

Neuropeptide innervation and neuroendocrine cells in allergic rhinitis and chronic hypertrophic rhinitis

The neuropeptides and neuroendocrine cells are proven to exist in the human nasal mucosa. However, the pathophysiological and neuroimmunological roles of regulatory peptides in human nasal diseases require further investigation.

The interplay between alcohol consumption, oral hygiene, ALDH2 and ADH1B in the risk of head and neck cancer

Alcohol consumption is an established risk factor for head and neck cancer (HNC). The major carcinogen from alcohol is acetaldehyde, which may be produced by humans or by oral microorganisms through the metabolism of ethanol. To account for the different sources of acetaldehyde production, the current study examined the interplay between alcohol consumption, oral hygiene (as a proxy measure for the growth of oral microorganisms), and alcohol‐metabolizing genes (ADH1B and ALDH2) in the risk of HNC. We found that both the fast (*2/*2) and the slow (*1/*1 + *1/*2) ADH1B genotypes increased the risk of HNC due to alcohol consumption, and this association differed according to the slow/non‐functional ALDH2 genotypes (*1/*2 + *2/*2) or poor oral hygiene. In persons with the fast ADH1B genotype, the HNC risk associated with alcohol drinking was increased for those with the slow/non‐functional ALDH2 genotypes. For those with the slow ADH1B genotypes, oral hygiene appeared to play an important role; the highest magnitude of an increased HNC risk in alcohol drinkers occurred among those with the worst oral hygiene. This is the first study to show that the association between alcohol drinking and HNC risk may be modified by the interplay between genetic polymorphisms of ADH1B and ALDH2 and oral hygiene. Although it is important to promote abstinence from or reduction of alcohol drinking to decrease the occurrence of HNC, improving oral hygiene practices may provide additional benefit.

The expression of human antimicrobial peptide LL-37 in the human nasal mucosa.

Background LL-37, an antimicrobial peptide, has been discovered to be produced by a number of epithelial cells. It is identified as a key element in the innate host defense mechanism. Because little is known about the expression of LL-37 in human sinonasal tract, we conducted this study to investigate the expression of LL-37 in human nasal mucosa. Methods We investigated the expression of LL-37 gene by the reverse transcription polymerase chain reaction (RT-PCR) and localization of LL-37 peptide by immunohistochemistry in the inferior turbinate mucosa of 7 normal subjects and the nasal polyps of 12 patients with chronic paranasal sinusitis. Results The transcripts of the LL-37 gene were detected in all human nasal tissues analyzed by RT-PCR. There is a significant increase of LL-37 mRNA expression in nasal polyps as compared with the normal nasal mucosa. Using immunohistochemistry, LL-37 peptide was localized in surface epithelial cells and submucosal glands. Conclusions Our findings suggest that LL-37 is expressed by nasal mucosa and is upregulated during inflammation.

Mucosal changes in rhinitis medicamentosa.

To evaluate the nasal mucosal changes in rhinitis medicamentosa (RM), especially those related to goblet cells and subepithelial glands, we studied specimens of the inferior turbinate mucosa from 8 patients with RM, 8 patients with chronic hypertrophic rhinitis (CHR), and 5 patients with normal nasal mucosa. All specimens were assessed by electron microscopy and immunohistochemical study. Under a scanning electron microscope, hyperplasia of goblet cells was most prominent in the RM group, and an increased number of gland openings was evident in the RM and CHR groups. In addition, the immunoreactivity of epidermal growth factor receptor staining was strongest in the hyperplastic epithelium of the RM group. According to our results, it is feasible that the mucosa of patients with RM is in a chronic inflammatory, hypersecretory state. Degenerative changes in the secretory elements may cause impairment of mucociliary transport and may be responsible for the nasal obstruction and posterior nasal drip in RM.

Assessment of p53 protein expression in normal mucosa and benign and malignant lesions of the nasal cavity.

p53 gene mutation is documented in head and neck cancer. No reports exist relating this mutation to normal mucosa or benign and malignant lesions of the nasal cavity. We investigate p53 overexpression using immunohistochemical techniques improved by an antigen retrieval method. p53 protein was analyzed in the following cases: normal, benign [papilloma and inverted papilloma (IP)] and malignant [squamous-cell carcinoma (SCC) arising in IP, SCC alone, adenocarcinoma and small-cell carcinoma]. Both the intensity and rate of positive p53 immunostaining were evaluated using a quantitative AutoCAD program. Overexpression of p53 protein was not identified in normal mucosa, benign or premalignant lesions; however, approximately 60% is correlated to nasal cancer. p53 overexpression correlates with heavy smoking. Both the IP and SCC portions of SCC synchronous with IP showed similar p53 immunoreactivity. SCC arising in IP shows a lower p53 immunoreactivity than SCC alone. Thus, smoking along with a p53 mutation may be a mutagenic agent in nasal cancers. Alteration of the p53 protein may play an important role in the early stages of the malignant transformation of IP. A low p53 immunoreactivity indicates the presence of wild-type p53 protein. This may show a better response to radiation therapy yielding a better prognosis for SCC arising in IP compared to SCC alone. However, further clinical trials are required to investigate this possibly worthwhile prognostic marker.

A survey on the management of acute rhinosinusitis among Asian physicians

BACKGROUND Based on the `European Position Paper on Rhinosinusitis and Nasal polyps (EP3OS 2007)`, this study aimed to investigate general practitioners (GPs) and other specialists` understanding when managing patients with acute rhinosinusitis (ARS) in Asia. METHODOLOGY Among a total of 2662 questionnaires completed, 2524 (94.8%) were valid for analysis. There were 1308 GPs (51.8%), 989 otolaryngologists (39.2%) and 227 paediatricians (9%) from Mainland China, Hong Kong, Indonesia, India, Malaysia, Pakistan, Philippines, Singapore, Thailand and Taiwan. RESULTS ARS is affecting an estimated 6 - 10% of patients seen in a daily out-patient practice. The EP3OS criteria are well supported by Asian physicians (94.1%). Most physicians (62.7%) agreed that radiological investigation is not needed to diagnose ARS. However, even for mild ARS (common cold), medical treatments were still recommended by 87% of GPs, 83.9% of otolaryngologists, and 70% of paediatricians. The top three first-line treatments prescribed were antihistamines (39.2%), nasal decongestants (33.6%), and antibiotics (29.5%). Antibiotics usage increased as the first line treatment of moderate (45.9%) and severe (60.3%) ARS. CONCLUSION ARS is commonly managed by GPs, otolaryngologists, and paediatricians in Asia. However, understanding of the management of ARS needs further improvement to minimize unnecessary use of radiological investigations, overuse of antibiotics, and under use of nasal corticosteroids.

Expression of human β-defensin 2 in human nasal mucosa

Human β-defensin (HBD)-2, an antimicrobial peptide, has been discovered to be produced by a number of epithelial cells. It is identified as a key element in the innate host defense mechanism. Because little is known about the expression of HBD-2 in the human sinonasal tract, we conducted this study to investigate the expression of the HBD-2 mRNA gene by the reverse transcription polymerase chain reaction (RT-PCR) and localization of HBD-2 peptide by immunohistochemistry in human nasal inferior turbinates and nasal polyps. RT-PCR showed significantly higher expression of HBD-2 mRNA in nasal polyps than in inferior turbinates. Using immunohistochemistry, HBD-2 peptide was predominately localized in surface epithelial cells. Thus, it is feasible that HBD-2 is expressed in nasal mucosa and is upregulated in a condition of chronic inflammation.

Overexpression of Fas-Ligand in Human Nasal Polyps

Apoptosis mediated through the Fas/Fas-L system is essential in regulating immune function, developing organs, and conferring immune privilege. To illustrate the role of the Fas/Fas-L system in the pathogenesis of human nasal polyps, we investigated the transcripts and protein level of the Fas-L gene in 8 human nasal polyp tissues and 7 nasal turbinate mucosa specimens using reverse transcription—polymerase chain reaction and Western blotting. Localization of Fas-L was performed with immunohistochemistry. The transcripts of the Fas-L gene were detected at similar levels in both polyps and nasal mucosa. There was a significant overexpression of Fas-L protein on nasal polyps compared to nasal mucosa. Fas-L—positive cells were localized on the epithelial layers of cystically dilated glands and the down-growing epithelium of nasal polyps. Fas-L may play an important role in the pathogenesis of human nasal polyps, including cystic degeneration of submucosal glands and conferring of immune privilege to nasal polyp formation.

Analysis of the expression of Fas-L in nasopharyngeal carcinoma tissues.

Nasopharyngeal carcinoma (NPC) is an epithelial cancer with a high incidence in Southeast Asia. How it escapes attack from the host immune system is not fully understood. Recently, pieces of evidence show that Fas-ligand (Fas-L)-mediated apoptosis may be involved in immune privilege of tumours. To determine whether a similar mechanism may exist in NPC, the expression of Fas-L was analysed. Biopsy specimens of the nasopharynx were taken from 27 NPC patients. Histologically, they were either non-keratinizing or undifferentiated carcinomas. Nasopharyngeal biopsies of 11 other patients that proved to have no tumour served as control. The transcripts of Fas-L were detected by reverse transcription-polymerase chain reaction. Localization of Fas-L protein was performed with immunohistostaining using an antibody recognizing human Fas-L. All nasopharyngeal tissues have a similar amount of transcripts of Fas-L. However, the Fas-L protein was detected exclusively on the cell surface of malignant epithelial cells of NPC. The present findings suggest that Fas-L protein may be involved in evading immune attack of NPC.