title: Expression of thymidylate synthase and dihydropyrimidine dehydrogenase in primary oral squamous cell carcinoma and corresponding metastases in cervical lymph nodes: association with the metastasis suppressor CD82.
abstract: Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are 5-fluorouracil (5-FU) metabolizing enzymes and are involved in the sensitivity of carcinoma patients to 5-FU. Although 5-FU is often used for the treatment of oral carcinoma, there has not been any investigation into the expression of these enzymes in metastatic lymph nodes or of their roles in the effectiveness of 5-FU in treating lymph node-metastatic cancer. Oral squamous cell carcinoma (OSCC) often metastasizes to the lymph nodes, and these enzymes may be significant in the survival of patients with this disease. This study investigated the expression of TS and DPD in cervical lymph node metastases and its relationship with primary OSCC, as well as the interaction between these enzymes and Kangai 1(KAI1/CD82) which is a metastasis suppressor protein. Surgical specimens from 20 cases of OSCC with lymph node metastasis, 20 cases of OSCC without lymph node metastasis, and 10 cases of normal mucosa were examined by immunohistochemistry. The relationship between TS and DPD expression and clinicopathological data was analyzed. TS and DPD proteins were overexpressed in primary OSCC compared to that in normal mucosa. TS expression of the primary oral cancer cells in the group with lymph node metastasis was higher than that of those without. DPD expression did not significantly correlate with the occurrence of lymph node metastasis, nor was it different between primary oral cancer cells and cervical metastases. CD82 expression was significantly reduced in lymph node metastases. These findings indicate that TS and CD82 may be of great value in assessing lymph node metastasis of OSCC, and could be taken as new targets for therapy of metastatic OSCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. gkawa@net.nagasaki-u.ac.jp
authors.forename: Goro
authors.initials: G
authors.lastname: Kawasaki
authors.forename: Izumi
authors.initials: I
authors.lastname: Yoshitomi
authors.forename: Souichi
authors.initials: S
authors.lastname: Yanamoto
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Akio
authors.initials: A
authors.lastname: Mizuno
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umeda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051861:Kangai-1 Protein / Q000378:metabolism*; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology; D013940:Thymidylate Synthase / Q000378:metabolism*
chemical_list: C497688:CD82 protein, human; D051861:Kangai-1 Protein; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase