Prognostic significance of cyclin A in gastric cancer

• Published in: International journal of cancer 2006-10, Vol.119 (8), p.1897-1901
• Main Authors: Mrena, Johanna, Wiksten, Jan‐Patrik, Kokkola, Arto, Nordling, Stig, Haglund, Caj, Ristimäki, Ari
• Format: Article
• Language: English
• Subjects: Aged; Antigens, Surface - metabolism; Biological and medical sciences; cyclin A; Cyclin A - immunology; Cyclin A - metabolism; ELAV Proteins; ELAV-Like Protein 1; Female; Follow-Up Studies; gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; Humans; HuR; Immunohistochemistry; Male; Medical sciences; Prognosis; RNA-Binding Proteins - metabolism; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; survival; Survival Rate; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21944

High level of cyclin A promotes carcinogenesis, and overexpression of cyclin A has been associated with poor prognosis of cancer patients. We validated the prognostic role of cyclin A in gastric cancer and evaluated its correlation with expression of an mRNA stability factor HuR. From 342 consecutive histologically confirmed gastric cancer patients were obtained 325 representative tissue specimens for cyclin A and 316 for HuR immunohistochemistry. Specimens were stained by cyclin A and HuR specific monoclonal antibodies. Nuclear immunostaining detected in ≥≥≥≥5% of the tumor cells was considered the cut‐off for cyclin A positivity. Positive HuR immunoreactivity was scored as nuclear or cytoplasmic. Associations between scores, clinicopathological factors and survival were calculated by the χ2‐test, Fisher's exact test, Kaplan‐Meier test and Cox model. Cyclin A detected in the nuclei of cancer cells was positive in 55% (179 of 325) of the specimens; 40% (127 of 316) of the specimens had cytoplasmic and 88% (279of 316) nuclear immunoreactivity of HuR. Cyclin A expression was an independent prognostic factor for poor survival. Cyclin A immunoreactivity was associated with old age, high stage, proximal location of the tumor, intestinal type, noncurative resection, advanced penetration depth and with nodal metastases but not distant metastases. Furthermore, cyclin A expression was associated with cytoplasmic HuR expression, whereas no association with nuclear HuR was evident. Cyclin A is an independent prognostic factor in gastric cancer, and one mechanism for its overexpression may depend on cytoplasmic localization of HuR. © 2006 Wiley‐Liss, Inc.