TY - JOUR
T1 - Polo-like kinase 1 as a biomarker in rectal cancers
AU - Lim, Stephanie Hui-Su
AU - Shin, J. S.
AU - Lee, C. S.
AU - Tut, T. G.
AU - Ng, W. T. W.
AU - Chua, Wei
AU - Dissanayake, I. U.
AU - Spring, Kevin
AU - Ng, Weng
AU - Bokey, Les
AU - Souza, Paul de
PY - 2014
Y1 - 2014
N2 - Background: Human polo-like kinase 1 (PLK1) is important in mitotic progression. It is overexpressed in many cancers including colorectal cancer. Decreased PLK1 expression has been associated with tumour regression and improved outcome. The aim of our study is to investigate PLK1 in rectal cancers and its correlation with other variables and with overall survival (OS). Methods: Tissue microarrays were constructed from formalin-fixed and paraffin-embedded (FFPE) specimens of primary rectal or rectosigmoid cancer. Samples from the cancer centre (CC), cancer periphery (CP) and involved lymph nodes (LN) were stained for PLK1 by immunohistochemistry. Percentage of positive cells and staining intensity were scored and multiplied to give weighted scores (0-12), and dichotomised [low (0-5) or high (6-12)]. CC and CP scores were also averaged (CCCP). Results: 351 cases were identified, with median age of 72 years, 36% female, 64% male, 34% pT1/2, 66% pT3/4, 45% node-positive and 7% metastatic (M1). Median follow up was 3.2 years and five year OS 58%. Twenty four percent received neoadjuvant and 31% adjuvant treatment. Median PLK1 score was three for CC and four for CP, and this was significantly different (paired t-test p<0.001). Low CP PLK1 was associated with the presence of metastases (Fisher’s exact test p=0.001). Cox regression analysis revealed low CCCP PLK1 to be borderline prognostic for improved OS (p=0.048, hazard ratio HR 0.43 to 1.00). Low CP and CCCP were significant for OS in the non-metastatic (M0) group (p=0.013, HR 0.39-0.90 and p=0.032, HR 0.38-0.96 respectively). Both remained independent prognostic factors in multivariate analyses. Low LN PLK1 expression was significant for improved OS (p=0.015, HR 0.27-0.87) in univariate and multivariate models. Age, tumor node metastasis (TNM) stage, grade, vascular invasion, perineural invasion and adjuvant chemotherapy were significant predictors of OS. Conclusions: PLK1 scores in CC and CP were significantly different. Low CP, and to a lesser extent CCCP, were predictive of OS in the M0 subgroup. In the entire cohort, only CCCP PLK1 was borderline significant for OS. There was an association between low CP PLK1 and the presence of metastases, which needs to be explored further, given low numbers in the M1 group. Low LN PLK1 was also a significant predictor of OS.
AB - Background: Human polo-like kinase 1 (PLK1) is important in mitotic progression. It is overexpressed in many cancers including colorectal cancer. Decreased PLK1 expression has been associated with tumour regression and improved outcome. The aim of our study is to investigate PLK1 in rectal cancers and its correlation with other variables and with overall survival (OS). Methods: Tissue microarrays were constructed from formalin-fixed and paraffin-embedded (FFPE) specimens of primary rectal or rectosigmoid cancer. Samples from the cancer centre (CC), cancer periphery (CP) and involved lymph nodes (LN) were stained for PLK1 by immunohistochemistry. Percentage of positive cells and staining intensity were scored and multiplied to give weighted scores (0-12), and dichotomised [low (0-5) or high (6-12)]. CC and CP scores were also averaged (CCCP). Results: 351 cases were identified, with median age of 72 years, 36% female, 64% male, 34% pT1/2, 66% pT3/4, 45% node-positive and 7% metastatic (M1). Median follow up was 3.2 years and five year OS 58%. Twenty four percent received neoadjuvant and 31% adjuvant treatment. Median PLK1 score was three for CC and four for CP, and this was significantly different (paired t-test p<0.001). Low CP PLK1 was associated with the presence of metastases (Fisher’s exact test p=0.001). Cox regression analysis revealed low CCCP PLK1 to be borderline prognostic for improved OS (p=0.048, hazard ratio HR 0.43 to 1.00). Low CP and CCCP were significant for OS in the non-metastatic (M0) group (p=0.013, HR 0.39-0.90 and p=0.032, HR 0.38-0.96 respectively). Both remained independent prognostic factors in multivariate analyses. Low LN PLK1 expression was significant for improved OS (p=0.015, HR 0.27-0.87) in univariate and multivariate models. Age, tumor node metastasis (TNM) stage, grade, vascular invasion, perineural invasion and adjuvant chemotherapy were significant predictors of OS. Conclusions: PLK1 scores in CC and CP were significantly different. Low CP, and to a lesser extent CCCP, were predictive of OS in the M0 subgroup. In the entire cohort, only CCCP PLK1 was borderline significant for OS. There was an association between low CP PLK1 and the presence of metastases, which needs to be explored further, given low numbers in the M1 group. Low LN PLK1 was also a significant predictor of OS.
KW - rectum
KW - cancer
KW - biochemical markers
UR - http://handle.uws.edu.au:8081/1959.7/uws:35351
M3 - Article
SN - 1527-7755
SN - 0732-183X
VL - 32
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 15 supp.
M1 - e14542
ER -