The apoptotic and proliferation rate of tumour budding cells in colorectal cancer outlines a heterogeneous population of cells with various impacts on clinical outcome

Dawson, Heather; Kölzer, Viktor; Karamitopoulou, Evanthia; Economou, Mary; Hammer, Caroline; Müller, Dominique-Elisabeth; Lugli, Alessandro; Zlobec, Inti (2014). The apoptotic and proliferation rate of tumour budding cells in colorectal cancer outlines a heterogeneous population of cells with various impacts on clinical outcome. Histopathology, 64(4), pp. 577-584. Blackwell Scientific Publications 10.1111/his.12294

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AIMS In colorectal cancer (CRC), tumour buds represent an aggressive cell type at the invasive front with apparently low proliferation. The aim of this study was to determine proliferation and apoptotic rates of buds in comparison to tumour centre, front and mucosa. METHODS AND RESULTS Whole tissue sections from 188 CRC patients underwent immunohistochemistry for Ki67. Ten high-power fields (HPFs) were evaluated in mucosa, tumour centre, tumour front and tumour buds (total = 40 HPFs/case). Caspase-3 and M30 immunohistochemistry were performed on a multipunch tissue microarray from the same cohort. Ki67, caspase-3 and M30 immunoreactivity were correlated with outcome. The average percentage of cells showing Ki67 positivity was 5.2% in mucosa, and was not significantly different between the centre and front of the tumour (38.2% and 34.9%; P < 0.0001); 0.3% of buds showed Ki67 positivity (P < 0.0001). Caspase-3 expression was similar in mucosa, tumour centre and tumour front, but lower in tumour buds (<0.1%; P < 0.0001). M30 staining in buds was decreased (0.01%; P < 0.0001) in comparison to other areas. Ki67 positivity in buds was detrimental to survival in univariate (P = 0.0352) and multivariate (P = 0.0355) analysis. Caspase-3-positive tumours showed better outcome than negative tumours (P = 0.0262); but tumours with caspase-3-positive buds showed a worse outcome than those with caspase-3-negative buds (P = 0.0235). CONCLUSIONS Ki67, caspase-3 and M30 staining is absent in most tumour buds, suggesting decreased proliferation and apoptosis. However, the fact that Ki67 and caspase-3 immunoreactivity was associated with unfavourable prognosis points to a heterogeneous population of tumour buds.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Dawson, Heather; Kölzer, Viktor; Karamitopoulou, Evanthia; Economou, Mary; Hammer, Caroline; Müller, Dominique-Elisabeth; Lugli, Alessandro and Zlobec, Inti

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0309-0167

Publisher:

Blackwell Scientific Publications

Language:

English

Submitter:

Andrea Arnold

Date Deposited:

02 Apr 2014 13:54

Last Modified:

13 Feb 2017 09:57

Publisher DOI:

10.1111/his.12294

PubMed ID:

24111856

Uncontrolled Keywords:

anoikis, apoptosis, colorectal cancer, proliferation, tumour budding

BORIS DOI:

10.7892/boris.45957

URI:

https://boris.unibe.ch/id/eprint/45957

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