Cell Cycle Proteins Predict Recurrence in Stage II and III Colon Cancer

Abstract

Purpose. To investigate the prognostic value of multiple cell cycle-associated proteins in a large series of stage II and III colon cancers. Methods. From formalin-fixed, paraffin-embedded tumor samples of 386 patients with stage II and III colon cancer, DNA was isolated and tissue microarrays were constructed. Tissue microarray slides were immunohistochemically stained for p21, p27, p53, epidermal growth factor receptor, Her2/Neu, b-catenin, cyclin D1, Ki-67, thymidylate synthase, and Aurora kinase A (AURKA). Polymerase chain reaction-based microsatellite instability analysis was performed to allow for stratification of protein expression by microsatellite instability status. Results. Overall, low p21, high p53, low cyclin D1, and high AURKA expression were significantly associated with recurrence (P = 0.01, P \ 0.01, P = 0.04, and P \ 0.01, respectively). In stage II patients who did not receive adjuvant chemotherapy (n = 190), significantly more recurrences were observed in case of low-p21 and highp53-expressing tumors (P \ 0.01 and P = 0.03, respectively). In stage III patients who did not receive chemotherapy, high p53 expression was associated with recurrence (P = 0.02), and in patients who received chemotherapy, high AURKA expression was associated with relapse (P \ 0.01). In patients with microsatellite stable tumors, high levels of p53 and AURKA were associated with recurrence (P = 0.01 and P \ 0.01, respectively). Multivariate analysis showed p21 (odds ratio 1.6, 95% confidence interval 0.9-2.8) and AURKA (odds ratio 2.7, 95% confidence interval 1.3-5.6) to be independently associated with disease recurrence. Conclusions. p21, p53, cyclin D1, and AURKA could possibly be used as prognostic markers to identify colon cancer patients with high risk of disease recurrence.

A Prognostic Model To Predict Survival In Stage III Colon Cancer Patients Based on Histological Grade, Preoperative Carcinoembryonic Antigen Level and the Neutrophil Lymphocyte Ratio

“…Many genes and proteins had been uncovered as participated in the development and metastasis of colon cancer, and those genes and proteins also showed correlation with OS of stage III colon cancer patients (Bertagnolli et al, 2009;Ogino et al, 2009;Ogino et al, 2012;Belt et al, 2012). Indeed, the knowledge about those biomacromolecule provide us in-depth understanding about cancers.…”

“…In recent years, neutrophil lymphocyte ratio (NLR), which is thought as an indicator of systemic inflammation (Chiang et al, 2012), also has been reported as a prognostic factor for poor overall survival (OS) in colon cancer patients (Chiang et al, 2012). What's more, correlations between survival and several of genes or proteins, including KRAS (Ogino et al, 2009), BRAF (Ogino et al, 2012, microsatellite instability (Bertagnolli et al, 2009), cell cycle proteins (Belt et al, 2012) and MMP (Wong et al, 2011), were also observed. However, the available published papers still leave some to be desired.…”

Prognostic value of Aurora kinase A (AURKA) expression among solid tumor patients: a systematic review and meta-analysis

“…All eligible studies were published between 2005 and 2014. All TNM Stages (I-IV) were considered in 18 studies (46.2%) (9,18,20,27,28,30,(34)(35)(36)(37)(38)40,43,44,50,55,56,58), non-metastatic solid tumors (including Stage I-III or localized disease, based solely on singlestage disease or mixture of tumor stages) were considered in 12 (30.8%) studies (22,29,31,33,39,41,42,46,48,51,53,54); metastatic solid tumors (Stage IV) patients were considered in four studies (10.2%) (23,45,49,57); disease stage was not available were considered in five studies (12.8%). Four studies analyzing AURKA mRNA expression used real-time reverse transcription PCR (RT-PCR) (20,34,35,45); one study analyzing AURKA gene amplification by fluorescence in situ hybridization (FISH) (54); the other one used immunohistochemical (IHC) staining and RT-PCR (47); and the remaining 33 studies applied a immunohistochemistry detection method (9,18,19,21-23,27-33, 36-44,46,48-53,55-58).…”

Extent and Location of Tumor-Infiltrating Lymphocytes in Microsatellite-Stable Colon Cancer Predict Outcome to Adjuvant Active Specific Immunotherapy

“…For example, KRAS mutations and specific TP53 mutations are correlated with a relatively poor prognosis (6,7). Low expression of p21 and cyclin D1 and high expression of p53 and AURKA cell-cycle proteins have been correlated with disease recurrences (8). Conversely, patients with MSI tumors have a relatively good prognosis (9).…”