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Objectives: Evaluate preoperative and postoperative electrophysiological changes related to the accessory nerve with reference to dissection technique, modified radical neck dissection, and lateral neck dissection. Study Design: Prospective electrophysiological analysis of accessory nerve function in a total of 20 laryngeal carcinoma patients after neck dissection, 12 being lateral neck dissection (4 bilateral) and 8 being modified radical neck dissection. Methods: Distal latencies, compound muscle action potentials, and electromyography findings were investigated before surgery and, in early and late postoperative periods in 20 laryngeal carcinoma patients. Results were evaluated by Student t test and "x2 test for intragroup and intergroup differences. Results: In the lateral neck dissection group, postoperative distal latencies were longer, without statistical significance, whereas in the modified radical neck dissection group postoperative latencies were statistically longer. Postoperative compound muscle action potentials were significantly lower in both groups. Electromyographic work-up showed deterioration in early postoperative periods and improvement in late postoperative periods. When intergroup differences were compared, both postoperative compound muscle action potential and electromyographic findings were worse in the lateral neck dissection group. Conclusions: The accessory nerve function after modified radical neck dissection is better than function after lateral neck dissection because of increased stress applied to the nerve during retraction of the sternocleidomastoid muscle for achievement of a better exposed surgical field in lateral neck dissection.

Epithelial-mesenchymal-transition (EMT) is a critical step in tumor invasion and metastasis, while its fate is mainly defined by the balanced expression between the miR-200 family and ZEB transcription factors. In this study, we observed a reciprocal correlation between miR-200c/mir-141 and ZEB1, as well as between ZEB2 and E-cadherin expression in a panel of 13 head and neck squamous cell carcinoma (HNSCC) cell lines. We also confirmed that the enforced expression of miR-200c and miR-141 significantly reduced the migration capacity of HNSCC cells. Accordingly, the enforced expression of miR-200c and mir-141 resulted in a significant upregulation in E-cadherin expression, contrary to the significant downregulation in ZEB1 expression in 3 cell lines (UTSCC-24A, UTSCC-24B and UTSCC-6A cells). Another pair of cell lines, UTSCC-60A and UTSCC‑ 60B failed to show a significant change in the expression of E-cadherin or ZEB1/ZEB2 during the enforced expression of miR-200c/miR-141. To address the issue, we focused on the hypermethylation status of the ZEB1/2 promoters, which have both been shown to include wide CpG islands. We observed a marked upregulation in both ZEB1 and ZEB2 mRNA expression following treatment with a demethylating agent in both pairs of UTSCC cell lines. In conclusion, our findings confirm the existence of a reciprocal correlation between the mir-200 family and the ZEB family, and demonstrate the role of the miR-200 family in EMT, as well as in the migration and invasion ability of HNSCC cells. Furthermore, our data suggest that the promoter hypermethylation of ZEB1 and ZEB2 may play an essential role and may overshadow the effects of the miR-200 family in the regulation of EMT during carcinogenesis.

SUMMARY:Head and neck squamous cell carcinoma (HNSCC) is a frequent malignancy with a poor survival rate. Identifying the tumor suppressor gene (TSG) loci by genomic studies is an important step to uncover the molecular mechanisms involved in HNSCC pathogenesis. We therefore performed comprehensive analyses on loss of heterozygosity (LOH) using a genome-wide panel of 191 microsatellite markers in 22 HNSCC samples. We found 53 markers with significantly high LOH (Ͼ30%) on 21 chromosomal arms; the highest values of those were observed on 3p, 9p, 13q, 15q, and 17p, corresponding to D3S2432 (67%), D9S921-D9S925 (67%) and GATA62F03 (86%), D13S1493 (60%), D15S211 (62%), and D17S1353 (88%), respectively. Fifteen hot spots of LOH were defined in 13 chromosomal arms: 2q22-23, 4p15.2, 4q24-25, 5q31, 8p23, 9p23-24, 9q31.3, 9q34.2, 10q21, 11q21-22.3, 14q11-13, 14q22.3, 17p13, 18q11, and 19q12 as loci reported previously in HNSCCs. Furthermore, we identified five novel hot spots of LOH on three chromosomal arms in HNSCC at 2q33 (D2S1384), 2q37 (D2S125), 8q12-13 (D8S1136), 8q24 (D8S1128), and 15q21 (D15S211). In conclusion, our comprehensive allelotype analyses have unveiled and confirmed a total of 20 possible TSG loci that could be involved in the development of HNSCC. These results provide useful clues for identification of putative TSGs involved in HNSCC by fine mapping of the suspected regions and subsequent analysis for functional genes. (Lab Invest 2003, 83:99 -105). Head and neck squamous cell carcinomas (HNSCCs) are a diverse group of cancers and are frequently aggressive in their biologic behavior. They account for 1% to 2% of all cancer deaths in both the United States and Japan. Most patients with this malignancy have advanced disease at presentation, with regional disease in 43% and distant metastases in 10% (Pfister et al, 1997). The overall survival rate for this disease group remains poor, largely because of the high incidence of recurrent disease at the primary site or in the regional lymph nodes. Patients presenting with HNSCC also demonstrate a high incidence of second primary tumors in the upper aerodigestive tract, which may be synchronous or metachronous.In neoplastic progression, most of the sporadic solid tumors result from a multistep process of accumulated genetic and epigenetic alterations (Renan, 1993). Among these changes, inactivation of the tumor suppressor genes (TSGs) is one of the most critical steps. In this process, the deletion of targeted chromosomal regions eliminates the one allele, while inactivating events (mutation, deletion, or promoter hypermethylation) affect the other allele of the concerning TSG (Knudson, 1971). The detection of frequent loss of heterozygosity (LOH) in a chromosomal locus is considered to be critical evidence for the localization of a TSG. Large-scale genomic studies identified the chromosomal locations of several different human TSGs. A substantial number of TSGs involved in the genesis of several cancer types, including HNSCCs, have already been discovered. ...

We analysed the loss of heterozygosity (LOH) of long arm of chromosome 2 by using 16 polymorphic microsatellite markers in 39 matched oral normal and cancer tissues, and defined the deletional mapping of the region with putative tumor suppressor genes. LOH was detected at least one location in 33 of 39 (85%) tumor tissues. Frequent deletions were detected at the locations of microsatellite markers, D2S2304 (35%), D2S111 (40%), D2S155 (35%), D2S1327 (29%), D2S164 (29%), D2S125 (68%) and D2S140 (32%). Three preferentially deleted regions at 2q21-24, 2q33-35 and 2q37.3 were observed. Several candidate tumor suppressor genes in these regions such as LRP1B, CASP8, CASP10, BARD1, ILKAP, PPP1R7, and ING5, are located. Further molecular analysis of each gene should be performed to clarify their roles in oral carcinogenesis.