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

Abstract

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.

Immunohistochemical estimation of cell cycle phase in laryngeal neoplasia

“…In the normal larynx, Mcm-2 expression was confined to the basal layers of the epithelium, with the surface epithelium failing to show any Mcm-2 expression, as described previously (Chatrath et (Chatrath et al, 2003). In keeping with our findings at other anatomical sites (Freeman et al, 1999), the highest LI values were observed in the less well differentiated SCCs.…”

“…Features predictive of tumour aggression and poor ultimate survival are not consistently demonstrated on histopathological evaluation (Gale et al, 2000), giving rise to an inevitable degree of subjectivity and variability in diagnosis (Hellquist et al, 1999). Given the potentially mutilating and functionally disabling nature of aggressive laryngeal surgical interventions, a drive towards earlier detection and more reliable stratification of laryngeal dysplastic and malignant lesions would be welcome and indeed is essential if further attempts to improve quality of life and outcome are to be realised (Chatrath et al, 2003).…”

“…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).…”

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

“…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).…”

Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma

“…Most of these studies focused on the detection of MCM2 (Freeman et al, 1999;Chatrath et al, 2003;Davidson et al, 2003;Kodani et al, 2003;Scott et al, 2004). So far only few investigations studied MCM6 expression (Labib et al, 2001;Helfenstein et al, 2004).…”