DNA ANALYSIS OF HUMAN CHOLESTEATOMAS

Hypothesis: The hypothesis tested in this article is that if cholestea tomas are a low-grade squamous cell neoplasm, then evidence of genetic instability, in the form of abnormal or aneuploid amounts of DNA, sho uld be evident. Background: Cholesteatoma is a destructive lesion of t he middle ear and/or mastoid process that produces complications by er osion of the temporal bone. The clinical hallmarks of cholesteatomas, namely invasion, migration, uncoordinated proliferation, altered diffe rentiation, aggressiveness, and recidivism, are traits typically assoc iated with the neoplastic cell. However, there is little evidence to s upport or refute the speculation that cholesteatomas are a low-grade s quamous cell neoplasm. The existence of defects in the genetic complem ent of the major cellular constituents comprising a cholesteatoma, fib roblasts and keratinocytes, would support the speculation that cholest eatomas are a neoplasm, since cancers commonly manifest quantitative a nd qualitative alterations in the normal euploid complement of genetic information, resulting in a cell that has an abnormal or aneuploid am ount of DNA. Methods: DNA content (ploidy) within cholesteatoma tissue s was measured by flow cytometry and image analysis. Results: The DNA content of 11 human cholesteatomas and nine postauricular skin specime ns was analyzed using flow cytometry, while the DNA content of 10 chol esteatoma specimens was analyzed using image analysis. interpretable d ata was obtained from 10 cholesteatoma specimens and six postauricular skin specimens. One cholesteatoma specimen demonstrated an abnormal a neuploid DNA content, whereas the remaining nine cholesteatomas and th e six postauricular skin specimens demonstrated a normal euploid DNA c ontent. Conclusions: We conclude that, due to the lack of overt geneti c instability, as evidenced by the presence of a normal euploid DNA co ntent, cholesteatomas are not low-grade neoplasms.