p12CDK2-AP1 is associated with tumor progression and a poor prognosis in esophageal squamous cell carcinoma

Abstract

Abstract. p12 CDK2-associating protein 1 (p12 CDK2-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 p12 CDK2-AP1 expression is known to be a negative prognostic indicator in patients with oral squamous cell carcinoma. To elucidate the role of p12 CDK2-AP1 expression in esophageal squamous cell carcinoma (ESCC), we immunohistochemically examined the expression of p12 CDK2-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 (≥25% of cancer cells showing p12 CDK2-AP1 expression), while 41 (34.2%) lacked the staining (<25% of cancer cells showing p12 CDK2-AP1 expression). Negative staining for p12 CDK2-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 p12 CDK2-AP1 negative-T1 ESCC was significantly higher than that in patients with p12 CDK2-AP1 positive one (P<0.05). These results suggest the downregulation of p12 CDK2-AP1 to be related to tumor aggressiveness and a poor prognosis in patients with ESCC.

Role of DNA methylation in head and neck cancer

“…In a study, aberrant promoter methylation of the CHFR gene was reported in patients with OSCC, while the gene was methylated minimally in the surrounding normal mucosa and no methylation was observed in the CHFR promoter in a healthy cohort (Baba et al 2009; Toyota et al 2003). …”