Analysis of minichromosome maintenance proteins as a novel method for detection of colorectal cancer in stool

Rjo., Davies; Freeman, Alex; Morris, Lydia; Bingham, Sheila; Dilworth, S. J.; Scott, Ian; Laskey, Ronald A.; Miller, Richard N.; Coleman, Nicholas

doi:10.1016/s0140-6736(02)08739-1

Cited by 134 publications

(117 citation statements)

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“…Mouse monoclonal antibodies raised against Mcm-2 (Mukherjee et al, 2001;Davies et al, 2002), Mcm-5 (Mukherjee et al, 2001) and Ki67 (Mib-1 clone, DAKO, Ely, UK) were used.…”

Section: Primary Antibodiesmentioning

confidence: 99%

“…Antibodies against MCMs detect more cells in tissues than other 'proliferation' markers such as Ki67 (Todorov et al, 1998;Williams et al, 1998;Freeman et al, 1999). We and others have shown that immunocytochemical staining for MCMs such as Mcm-2 or Mcm-5 may be of value in identifying malignant or premalignant lesions in a range of clinical specimens (Todorov et al, 1998;Williams et al, 1998;Freeman et al, 1999;Stoeber et al, 1999;Meng et al, 2001;Davies et al, 2002;Going et al, 2002;Hunt et al, 2002;Rodins et al, 2002).…”

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confidence: 99%

“…However, these studies were performed before modern cytological techniques were widely available. With the application of liquid-based cytological techniques, coupled with novel biomarkers used to detect neoplastic cells (Biscotti et al, 2002;Davies et al, 2002), laryngeal brushing may now represent a viable less-invasive technique for the detection of neoplasia in the larynx, as has been shown to be the case in cervix and colon (Williams et al, 1998;Davies et al, 2002).…”

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confidence: 99%

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Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions

et al. 2003

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Histological classification of laryngeal epithelial lesions is highly subjective, and methods of cytological detection are not well developed. Improved determination of aberrant cell cycle entry may allow increased objectivity in histological assessment and enable the development of less invasive diagnostic cytology tests. Sections of normal larynx (n ¼ 10), laryngeal dysplasia (n ¼ 20) and laryngeal squamous cell carcinoma (SCC) (n ¼ 10) were classified according to the Ljubljana classification and stained for markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67. Expression patterns were compared using double labelling confocal microscopy. There was a correlation between Mcm-2 and Ki67 labelling indices (r ¼ 0.93; 95% CI [0.84, 0.97]) and both markers showed increased expression from normal epithelium to SCC (Mcm-2, P ¼ 0.001; Ki67, P ¼ 0.0002). Importantly, there was minimal expression of Mcm-2 or Ki67 in the most superficial layers of normal larynx and abnormal or atypical hyperplasia, in contrast to carcinoma in situ and SCC. Clusters of Mcm-2/5-positive cells were present in cytological preparations from SCC, but not from those showing atypical hyperplasia or inflammation in non-neoplastic tissue. Minichromosome maintenance protein-2 staining may increase the objectivity and reliability of histological grading of laryngeal epithelial lesions. Laryngeal brushings, combined with immuno-enhanced liquid-based cytology, could be useful, as a less invasive approach, to the detection of laryngeal malignant and premalignant lesions.

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“…Mouse monoclonal antibodies raised against Mcm-2 (Mukherjee et al, 2001;Davies et al, 2002), Mcm-5 (Mukherjee et al, 2001) and Ki67 (Mib-1 clone, DAKO, Ely, UK) were used.…”

Section: Primary Antibodiesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions

et al. 2003

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“…In contrast, in pre-malignant cervical intraepithelial neoplasia (CIN), the cellular proliferative compartment expands in proportion to histological grade, resulting in MCM-positive cells being present at the epithelial surface. We demonstrated that such aberrant expression can be exploited to improve detection of abnormal cells in cervical smears (Williams et al, 1998) and subsequently showed that the principle can be extended to early detection of neoplasia at other sites, including large bowel (Davies et al, 2002), larynx (Chatrath et al, 2003) and oral cavity (Scott et al, 2006).…”

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confidence: 99%

MCM immunocytochemistry as a first line cervical screening test in developing countries: a prospective cohort study in a regional cancer centre in India

et al. 2007

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Cervical screening is not available for the majority of women in resource-poor countries. An important factor is a lack of skilled operators necessary for high-throughput assessment of the Papanicolaou (Pap) test currently in use. We compared the efficacy of immunocytochemistry for minichromosome maintenance (MCM) proteins vs standard Pap testing at detecting disease in 455 cervical smears processed in a typical Indian screening laboratory. Conventional (non-monolayer) smears were stained manually and then examined by a cytotechnologist and a cytopathologist. The MCM test was called positive when immunolabelled cells were identified as dyskaryotic by the Pap counterstain. The MCM test was read more quickly than the Pap test (approximately 2 vs 10 min) and there was 100% inter-observer agreement compared with 85% for Pap (Po0.0001). The MCM test detected 10 biopsy-proven cancers or pre-cancers that were not detected by Pap (P ¼ 0.002; P ¼ 0.016 excluding three cases where the Pap was deemed unsatisfactory on review). The cases in question included one recurrent squamous carcinoma and one adenocarcinoma in a screening patient who would have returned to 5 year recall. There were no false positive MCM test results. We propose that MCM immunocytochemistry has considerable advantages for cervical screening in developing countries like India.

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“…Minichromosome maintenance protein 2 is one of six MCM proteins (MCMs 2 -7) that assemble in the prereplication complex and are essential for DNA replication in eukaryotic cells (Kearsey and Labib, 1998 six proteins are abundant throughout the cell cycle but are broken down rapidly on differentiation and more slowly in quiescence (Musahl et al, 1998). Antibodies against Mcm-2 have previously been shown to detect more cycling cells in laryngeal tissues than other 'proliferation' markers such as Ki67 (Chatrath et al, 2003), and immunohistochemical staining for Mcm-2 and/or Mcm-5 has been shown to be of value in identifying malignant or premalignant lesions in a range of clinical specimens (Williams et al, 1998;Freeman et al, 1999;Davies et al, 2002;Going et al, 2002;Chatrath et al, 2003;Scott et al, 2003;Sirieix et al, 2003;Scott et al, 2004).…”

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confidence: 99%

Immunohistochemical estimation of cell cycle phase in laryngeal neoplasia

et al. 2006

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We previously developed an immunohistochemical method for estimating cell cycle state and phase in tissue samples, including biopsies that are too small for flow cytometry. We have used our technique to examine whether primary abnormalities of the cell cycle exist in laryngeal neoplasia. Antibodies against the markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67, and putative markers of cell cycle phase, cyclin D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis) were applied to paraffin-embedded sections of normal larynx (n ¼ 8), laryngeal dysplasia (n ¼ 10) and laryngeal squamous cell carcinoma (n ¼ 10). Cells expressing each marker were determined as a percentage of total cells, termed the labelling index (LI), and as a percentage of Mcm-2-positive cells, termed the labelling fraction (LF). The frequency of coexpression of each putative phase marker was investigated by confocal microscopy. There was a correlation between Mcm-2 and Ki67 LIs (r ¼ 0.93) but Mcm-2 LIs were consistently higher. All cells expressing a phase marker coexpressed Mcm-2, whereas Ki67 was not expressed in a proportion of these cells. The putative phase markers showed little coexpression. Labelling index values increased on progression from normal larynx through laryngeal dysplasia to squamous cell carcinoma for Mcm-2 (P ¼ 0.001), Ki67 (P ¼ 0.0002), cyclin D1 (P ¼ 0.015), cyclin A (P ¼ 0.0001) and cyclin B1 (P ¼ 0.0004). There was no evidence of an increase in the LF for any phase marker. Immunohistochemistry can be used to estimate cell cycle state and phase in laryngeal biopsies. Our data argues against primary cell cycle phase abnormalities in laryngeal neoplasia.

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Analysis of minichromosome maintenance proteins as a novel method for detection of colorectal cancer in stool

Cited by 134 publications

References 3 publications

Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions

Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions

MCM immunocytochemistry as a first line cervical screening test in developing countries: a prospective cohort study in a regional cancer centre in India

Immunohistochemical estimation of cell cycle phase in laryngeal neoplasia

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