title: 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=10), laryngeal dysplasia (n=20) and laryngeal squamous cell carcinoma (SCC) (n=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 (rho=0.93; 95% CI [0.84, 0.97]) and both markers showed increased expression from normal epithelium to SCC (Mcm-2, P=0.001; Ki67, P=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.
authors.affiliation: MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK.
authors.forename: P
authors.initials: P
authors.lastname: Chatrath
authors.forename: I S
authors.initials: IS
authors.lastname: Scott
authors.forename: L S
authors.initials: LS
authors.lastname: Morris
authors.forename: R J
authors.initials: RJ
authors.lastname: Davies
authors.forename: S M
authors.initials: SM
authors.lastname: Rushbrook
authors.forename: K
authors.initials: K
authors.lastname: Bird
authors.forename: S L
authors.initials: SL
authors.lastname: Vowler
authors.forename: J W
authors.initials: JW
authors.lastname: Grant
authors.forename: I T
authors.initials: IT
authors.lastname: Saeed
authors.forename: D
authors.initials: D
authors.lastname: Howard
authors.forename: R A
authors.initials: RA
authors.lastname: Laskey
authors.forename: N
authors.initials: N
authors.lastname: Coleman
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D004261:DNA Replication; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D064111:Minichromosome Maintenance Complex Component 2