The supplementary diagnostic power of selected immunohistochemical, molecular genetic and infective parameters in epithelial hyperplastic laryngeal lesions.
OBJECTIVE
MIB-1 and p53 protein expression, loss of heterozygosity (LOH), microsatellite instability (MSI) of di- and mononucleotide repeats, and HPV status were tested for their potential to characterize different stages of epithelial hyperplastic laryngeal lesions (EHLL).


METHODS
Thirty-two EHLL were reclassified according to the Ljubljana classification into simple (SH), abnormal (AbH), atypical hyperplasia (AtH) and carcinoma in situ, and investigated by immunohistochemical methods, PCR and direct sequencing analysis.


RESULTS
MIB-1 increased with progressive grades of EHLL, whereas p53 protein expression was distinctive only between SH and AbH. LOH showed increasing frequency with grades of the lesions, but the distribution of altered loci (9p, 9q, 10q, 11q, 17p) was not qualified to differentiate between the stages. MSI was detected in SH, AbH and AtH without clear correlation to histopathological grading. HPV infection occurred mostly in SH and AbH (both: 66.7%).


CONCLUSIONS
MIB-1 labeling and allelic loss could assist histopathological diagnosis in the entire spectrum of EHLL, whereas the MSI results point to a genetic instability of the laryngeal mucosa in general and are therefore not helpful in the distinction of different stages of EHLL. However, future molecular genetic analyses should consider more late events of laryngeal carcinogenesis to improve their diagnostic potential. Furthermore, our results indicate that nonrisky and risky EHLL could probably be caused by different exogenous factors.
Kleist
Britta
B
Institute of Pathology, University of Greifswald, Greifswald, Germany. kleist@uni-greifswald.de
Junghans
Dirk
D
Lorenz
Gerd
G
Bankau
Alexander
A
Poetsch
Micaela
M
D000368:Aged; D014408:Biomarkers, Tumor; D002278:Carcinoma in Situ / Q000175:diagnosis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis; D003937:Diagnosis, Differential; D005260:Female; D016368:Frameshift Mutation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D007818:Laryngeal Diseases / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000821:virology; D007822:Laryngeal Neoplasms / Q000175:diagnosis; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D020545:Respiratory Mucosa / Q000473:pathology / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014412:Tumor Virus Infections / Q000150:complications
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53