A novel immunohistochemical method to estimate cell-cycle phase distribution in archival tissue:Implications for the prediction of outcome in colorectal cancer

Scott, Ian S., Morris, Lesley S., Bird, Kate, Davies, R. Justin, Vowler, Sarah L., Rushbrook, Simon M., Marshall, Aileen E., Laskey, Ronald A., Miller, Richard, Arends, Mark J. and Coleman, Nicholas (2003) A novel immunohistochemical method to estimate cell-cycle phase distribution in archival tissue:Implications for the prediction of outcome in colorectal cancer. Journal of Pathology, 201 (2). pp. 187-197. ISSN 0022-3417

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Abstract

An immunohistochemical method for assessing cell-cycle phase distribution in colorectal resection specimens would enable phase data to be incorporated into diagnostic algorithms for the estimation of prognosis and response to adjuvant chemotherapy in colorectal. cancer. In contrast to flow cytometry, an immunohistochemical method would also allow the phase distribution to be examined within morphologically heterogeneous regions of neoplasms. Paraffin sections of normal colon (n = 25), colonic adenoma (n = 15), and colonic adenocarcinoma (n = 30) were analysed by immunohistochemistry using antibodies against markers of cell-cycle entry, Mcm-2 and Ki67, and putative markers of the cell-cycle phase, cyclins D1 and E (putative markers of G1 phase), cyclin A (S phase), cytoplasmic cyclin B1 (G2 phase), and phosphohistone H3 (M phase). The phase specificity of each marker was assessed by examining the degree of co-expression of adjacent phase markers using double-antibody fluorescence confocal microscopy and by comparison with flow cytometric analysis performed on adjacent tissue sections. The S-phase specificity of detectable cyclin A was also assessed in combination with in situ DNA replication using fluorescence confocal microscopy. All cells expressing phase markers co-expressed Mcm-2. Adjacent phase markers were not significantly co-expressed, confirming the relative specificity of these markers in tissue sections of colon. Cell-cycle phase distribution, calculated by immunohistochemistry, compared well with phase analyses obtained by flow cytometry. No cells expressed cyclin A in the absence of active DNA replication. The S-phase labelling index, as defined by detectable cyclin A expression, showed a positive correlation with the Mcm-2 labelling index and increased in the progression from normal colon to adenocarcinoma. In conclusion, a combination of these cell-cycle phase markers can be used to calculate the distribution of cells throughout each phase of the cell cycle in colorectal tissue sections. Detectable cyclin A can be used as a surrogate marker of S phase and may be of value in predicting prognosis and response to adjuvant therapy.

Item Type:	Article
Uncontrolled Keywords:	b1,cell-cycle regulation,colonic carcinoma,cyclins a,d1,minichromosome maintenance proteins,phosphohistone h3,s-phase fraction,pathology and forensic medicine ,/dk/atira/pure/subjectarea/asjc/2700/2734
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	https://www.scopus.com/pages/publication...
Depositing User:	LivePure Connector
Date Deposited:	30 Jun 2026 13:20
Last Modified:	30 Jun 2026 15:23
URI:	https://ueaeprints.uea.ac.uk/id/eprint/103527
DOI:	10.1002/path.1444

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