J Pathol Transl Med.  2017 Jan;51(1):32-39. 10.4132/jptm.2016.10.17.

Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma

• Koh HM
• Jang BG
• Hyun CL
• Kim YS
• Hyun JW
• Chang WY
• Maeng YH

• KMID: 2367678
• DOI: http://doi.org/10.4132/jptm.2016.10.17

Abstract

BACKGROUND
Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea.
METHODS
AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues.
RESULTS
AURKA gene amplification was found more frequently in the 20q13.2-13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001).
CONCLUSIONS
AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients.

Keyword

Aurora kinase A; Colorectal adenocarcinoma; Prognosis

MeSH Terms

Adenocarcinoma*
Aurora Kinase A*
Chromosomal Instability
Colorectal Neoplasms
Comparative Genomic Hybridization
Disease-Free Survival
Fluorescence
Gene Amplification
Humans
Immunohistochemistry
In Situ Hybridization
Korea
Male
Mitosis
Multivariate Analysis
Phosphotransferases
Prognosis
Proportional Hazards Models
Phosphotransferases

Figure

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  Fig. 1. (A) Genome wide array comparative genomic hybridization using DNA from colorectal carcinoma tissue showing copy number gains (block arrows) and losses (arrowheads) on multiple sites. (B) Copy number plots of chromosome 20 showing frequent gains in certain areas (line arrows).

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  Fig. 2. Fluorescence in situ hybridization for Aurora kinase A (AURKA) in colorectal carcinomas showing significant amplification in the 20q13.2–13.33 gain-positive case (A) and no amplification in the case with no copy number gain on 20q13.2 (B).

• 

  Fig. 3. Immunohistochemical staining with Aurora kinase A (AURKA). (A) Score 1, positive staining in <10%. (B) Score 2, positive staining in ≥10% and <25%. (C) Score 3, positive staining in ≥25% and <50%. (D) Score 4, positive staining in ≥50%.

• 

  Fig. 4. The relationships between Aurora kinase A (AURKA) expression (A), lymphatic invasion (B), perineural invasion (C), TNM stage (D) and progression-free survival were analyzed using the Kaplan-Meier method with the log-rank test to assess the differences in survival probability between the groups.

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