title: p12CDK2-AP1 is associated with tumor progression and a poor prognosis in esophageal squamous cell carcinoma.
abstract: p12 CDK2-associating protein 1 (p12CDK2-AP1) is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities. In addition, p12CDK2-AP1 has also been shown to interfere in DNA replication. A reduction of p12CDK2-AP1 expression is known to be a negative prognostic indicator in patients with oral squamous cell carcinoma. To elucidate the role of p12CDK2-AP1 expression in esophageal squamous cell carcinoma (ESCC), we immunohistochemically examined the expression of p12CDK2-AP1 protein in 120 resected ESCC specimens and determined its association with the clinicopathological characteristics and prognosis. Of the 120 ESCCs, 79 (65.8%) showed positive staining (>or=25% of cancer cells showing p12CDK2-AP1 expression), while 41 (34.2%) lacked the staining (<25% of cancer cells showing p12CDK2-AP1 expression). Negative staining for p12CDK2-AP1 was found to be significantly associated with advanced lesions [depth of tumor (P=0.001), lymph node metastasis (P<0.001), pathological stage (P<0.0001) and venous invasion (P<0.0001)], and a poor prognosis (disease-free survival and overall survival: log-rank P<0.05). The rate of lymph node metastasis in patients with p12CDK2-AP1 negative-T1 ESCC was significantly higher than that in patients with p12CDK2-AP1 positive one (P<0.05). These results suggest the down-regulation of p12CDK2-AP1 to be related to tumor aggressiveness and a poor prognosis in patients with ESCC.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University Hospital, Honjo, Kumamoto, Japan.
authors.forename: Yukiharu
authors.initials: Y
authors.lastname: Hiyoshi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Koutaro
authors.initials: K
authors.lastname: Hirashima
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Karashima
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Sato
authors.forename: Yu
authors.initials: Y
authors.lastname: Imamura
authors.forename: Youhei
authors.initials: Y
authors.lastname: Nagai
authors.forename: Naoya
authors.initials: N
authors.lastname: Yoshida
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Toyama
authors.forename: Naoko
authors.initials: N
authors.lastname: Hayashi
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000556:secondary / Q000601:surgery; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000032:analysis*; D014680:Veins / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C096151:CDK2AP1 protein, human; D025521:Tumor Suppressor Proteins