HER2 (c-erbB-2) has been suggested to be a prognostic factor in a variety of human cancers including breast, gastric and ovarian cancers. This study is therefore designed to ide~ntify changes of HER2 in nasopharyngeal carcinoma (NPC). an epithelia-derived malignancy with strong racial and geographic distribution. Interphase FISH and immunriohistochemical (IHC) staining were used to analyze the gene copy number and protein expression of HER2 in 45 cases of NPC from Guangzhou. Southern China. an area with the highest incidence of NPC in the world. Our results, however, found no significant alterations in gene copy number for HER2, although IHC staining detected expression of HER2 oncoprotein in 33% Of the 45 NPC tumors. No correlation was observed between HER2 expression and sex, age and clinical outcome of the patients. T stage, lymph node status, site and histopathological grading of-the tumors. These results cast doubt on the value of HER2 as a prognostic factor for NPC.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China, especially in the Guangdong area. To demonstrate a comprehensive profile of loss of heterozygosity (LOH) in NPC, we applied a large panel of 382 microsatellite polymorphism markers covering all the 22 autosomes in 98 cases of sporadic primary NPC. Of the 335 informative markers, 83 loci showed high level of LOH (presence in equal to or more than 30% cases) and most of the high frequent loci were clustered to chromosome 1p36 and 1p34, 3p14-p21, 3p24-p26, 3q25-q26 and 3q27, 4q31 and 4q35, 5q15-21 and 5q32-q33, 8p22-p23, 9p21-p23 and 9q33-q34, llp12-p14, 13q14-q13 and 13q 31-q32, 14q13-q11, 14q24-q23 and 14q32. High frequency of LOH was found in chromosomes 3, 5, 9 and 11 (≥50%), while medium frequency of LOH was found in chromosomes 1, 4, 6, 14, 17 and 19 (40-49%). Several new regions showing high frequency of LOH were found in chromosome 1p36, 3q25-q26, 3q27, 5q15-q21, 8p22-p23 and 11p12-14. The relationship between LOH and TNM stage of NPC was evaluated. Regions 6p23 (D6S289), 8p23.1 (D8S549) and 9q34.2 (D9S1826) showed higher frequency of LOH in later stages (Ⅲ and Ⅳ) than in earlier stages (Ⅰ and Ⅱ) (P<0.05). Thus, our study provides a global view on allelic loss in the development of NPC and should shed light on the way for localization of putative tumor suppressor genes associated with the pathogenesis of NPC.

Objective To gain a better understanding of genetic changes in Cantonese nasopharyngeal carcinoma (NPC). Methods Comparative genomic hybridization (CGH) was performed on 17 primary nasopharyngeal carcinomas.Results A novel copy number gain an chromosome 4q and loss of chromosome lp were found at a high frequency (>50%). Conclusions Current analysis revealed a comprehensive profile of the chromosomal regions showing gain of chromosomes 4q, 12q, and lq as well as loss of chromosomes 1p, 3p, 11q, 14q, 15q, 13q, Xq, 9q, 10p, 10q, and 16q. Frequently altered loci may encode oncogenes or tumor suppressor genes involved in the development of primary NPC.

Nonrandom allelic loss on chromosome 3p is a common event in nasopharyngeal carcinoma (NPC) with the implication that certain tumor suppressor gene(s) in this region are involved in the pathogenesis of these tumors, The BLU gene, located at 3p21.3, has recently been identified as a candidate tumor suppressor gene due to the occurrence of missense mutations and loss of its expression in lung cancer. To investigate the involvement of BLU gene in NPC, we examined tumors and cell lines. No pathogenic mutations were detected in the entire coding region of this gene in 45 primary NPC tumors and 5 NPC cell lines. While BLU was expressed in 100% (15 of 15) of noncancerous nasopharyngeal epithelia, its transcripts were missing in all 5 NPC cell lines, and absent or reduced mRNA levels were observed in 78% (2B of 36) of the primary tumors. In the NPC cell lines, loss of BLU expromoter sequence, and expression was restored after treatment with 5-aza-2-deoxycytidine. Methylation specific PCR analysis revealed that the BLU promoter was highly methylated in 74% (17 of 23) of primary tumors in which BLU was downregulated, whereas only 2 of 9 non-neoplastic nasophamoter region. The high incldence of BLU alterations suggests that it may be one of the critical tumor suppressor genes on chromosome 3p21.3 involved in the development of NPC.

To identify genetic alterations associated with the development and progression of human nasopharyngeal carcinoma (NPC), 57 tumors were analyzed by comparative genomic hybridization (CGH). In 47 cases, chromosomal imbalances were found. Several recurrent chromosomal abnormalities were identified in the present study. The most frequently detected chromosomal gains involved chromosome arms 12q (24 cases, 51%), 4q (17 cases, 36%), 3q (16 cases, 34%), 1q (15 cases, 32%), and 18q (15 cases, 32%). Common regions of gain involved 12q13-q15, 4q12-q21, and 3q21-q26. High-copy-number increases of chromosomal materials were detected in four chromosomal regions, 3q21-q26.2, 4p12-q21, 8p, and 12q14-q15. The most frequently detected loss of chromosomal materials involved chromosome arms 16q (26 cases, 55%), 14q (21 cases, 45%), 1p (20 cases, 43%), 3p (20 cases, 43%), 16p (19 cases, 40%), llq (17 cases, 36%), and 19p (16 cases, 34%). The most common regions of loss involved 14q24-qter, 1pter-p36.1, 3p22-p21.3, 11q21-qter, and the distal region of 19p. Genomic alterations detected by CGH were compared and found to be largely consistent with those identified in banding analysis and loss of heterozygosity studies. However, several previously unrecognized recurrent alterations were also identified in the present study, including gain of 4q and 18q, and loss of 16q, 14q, and 19p. In addition, gain of lq, 8q, 18q, and loss of 9q showed a statistically significant association with advanced clinical stages (P<0.05). Identification of recurrent sites of chromosomal gain and loss identify regions of the genome that may contain oncogenes or tumor suppressor genes, respectively, which may be involved in the tumorigenesis of NPC. Published 2000 Wiley-Liss, Inc.