In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 412-412
Abstract:
412 Background: Immune cell infiltrates play a key role in determining colorectal cancer outcome. It is unclear whether they are tumour or host specific. Increased immunogenicity may relate to senescence or proliferation. Senescence, a state of cell-cycle arrest, slows tumour progression. In animal models, senescence associated regression is mediated by upregulated antitumour immune responses. High proliferation may provoke immune responses. Relationships between senescence, proliferation and immune cell infiltrates have not previously been studied. We explore whether p16 ink4a associated senescence relates to T cell infiltrates in colorectal tumours and whether p16 ink4a expression, proliferation and T cell infiltrates confer similar survival relationships. Methods: Immunostaining of nuclear p16 inka and Ki67 was performed using a tissue microarray. Nuclear p16 inka and Ki67 were scored as high or low expression. (T cell markers CD3/CD45RO/CD8/FOXP3) were scored high/low grade on corresponding full sections (margin/stroma/ cancer cell nest). Results: 230 Stage I-III cancers were studied. High nuclear p16 ink4a was expressed in 63% and high proliferation (Ki67 〉 15% ) in 61%. P16 ink4a expression related to reduced margin, stroma and cancer cell nest (CCN) CD45RO cells (P=0.054, P=0.062, P=0.025) and reduced margin CD8 cells (P=0.016). High Ki67 labeling related to increased margin, and CCN CD3 cells (P=0.017, P 〈 0.001), increased margin and CCN CD45RO cells (P=0.023, P 〈 0.001), increased margin, stroma and CCN FOXP3 cells (P 〈 0.001, P=0.001, P 〈 0.001) and increased margin and CCN CD8 cells (P=0.026, P=0.001). On multivariate analysis, TNM stage (P 〈 0.001), low margin CD3 (P=0.014), low margin CD8 (P=0.037), low proliferation (Ki67) (P=0.013) and low senescence (P16 ink4a ) (P=0.002) conferred poorer cancer survival. Conclusions: p16 ink4a expression, proliferation and immune cell infiltrates are independent prognostic factors in colorectal cancer. Proliferation relates to increasing T cell infiltrates but independently influences survival. P16 ink4a associated senescence does not appear to mediate improved outcome by upregulating T cell responses. Relationships observed here suggest the opposite.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.4_suppl.412
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
detail.hit.zdb_id:
604914-X
Permalink