Proliferation, apoptosis, and survival in high-level microsatellite instability sporadic colorectal cancer

Michael-Robinson, J. M., Reid, L. E., Purdie, D. M., Biemer-Huttmann, A. E., Walsh, M. D., Pandeya, N., Simms, L. A., Young, J. P., Leggett, B. A., Jass, J. R. and Radford-Smith, G. L. (2001) Proliferation, apoptosis, and survival in high-level microsatellite instability sporadic colorectal cancer. Clinical Cancer Research, 7 8: 2347-2356.


Author Michael-Robinson, J. M.
Reid, L. E.
Purdie, D. M.
Biemer-Huttmann, A. E.
Walsh, M. D.
Pandeya, N.
Simms, L. A.
Young, J. P.
Leggett, B. A.
Jass, J. R.
Radford-Smith, G. L.
Title Proliferation, apoptosis, and survival in high-level microsatellite instability sporadic colorectal cancer
Journal name Clinical Cancer Research   Check publisher's open access policy
ISSN 1078-0432
1557-3265
Publication date 2001-08-01
Sub-type Article (original research)
Volume 7
Issue 8
Start page 2347
End page 2356
Total pages 10
Place of publication Philadelphia, Pennsylvania, U.S.A.
Publisher American Association for Cancer Research
Language eng
Subject C1
110316 Pathology (excl. Oral Pathology)
Abstract Sporadic colorectal cancer (CRC) characterized by high-level DNA microsatellite instability (MSI-H) has a favorable prognosis. The reason for this MSI-H survival advantage is not known. The aim of this study was to correlate proliferation, apoptosis, and prognosis in CRC stratified by MSI status. The proliferative index (PI) was measured by immunohistochemical staining with the Ki-67 antibody in a selected series of 100 sporadic colorectal cancers classified according to the level of MSI as 31 MSI-H, 29 MSI-Low (MSI-L), and 40 microsatellite stable (MISS). The Ki-67 index was significantly higher in MSI-H cancers (P < 0.0001) in which the PI was 90.1 1.2% (mean +/- SE) compared with 69.5 +/- 3.1 % and 69.5 +/- 2.3 % in MSI-L and MSS subgroups, respectively. There was a positive linear correlation between the apoptotic index (AI) and PI (r = 0.51; P < 0.001), with MSI-H cancers demonstrating an increased AI:PI ratio indicative of a lower index of cell production. A high PI showed a trend toward predicting improved survival within MSI-H cancers (P = 0.09) but did not predict survival in MSI-L or MSS cancers. The Al was not associated with survival in any MSI subgroup. In conclusion, this is the first study to show that sporadic MSI-H cancers are characterized by a higher AL:PI ratio and increased proliferative activity compared with MSI-L and MSS cancers, and that an elevated PI may confer a survival advantage within the MSI-H subset.
Keyword Oncology
Monoclonal-antibody Ki-67
Dna-replication Errors
Prognostic-significance
Cell-proliferation
Immunohistochemical Expression
Clinicopathological Variables
Protein Expression
Growth Fraction
Proximal Colon
Cyclin D1
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 00:57:04 EST