Author reply

Abstract

In response to the comment by Marangoz and Güllü that there was no rational election of patients to the normal group, we would like emphasize that there was a stated strategy for inclusion in that group, namely that the initial biopsy did not show any evidence of intraepithelial neoplasia.1 It is possible, as Marangoz and Güllü suggest, that metaplastic cells may possess some altered gene expression. However, the finding of metaplasia is a perfectly normal physiologic change within the cervix, and does not in any way represent intraepithelial neoplasia. Therefore, these patient samples also can be considered as normal. We also note that even if normal metaplastic cells express higher levels of c-myc and/or ras than normal nonmetaplastic cells, our results still would show that expression levels are unrelated to progression of cervical intraepithelial neoplasia. With regard to the immunohistochemical results, the 144 tissue samples tested for mutant ras expression all previously had tested positive with the pan-ras antibody. Although Marangoz and Güllü request further discussion regarding the possible significance of mutant ras protein observed in 17% of those 144 tissue samples, the presence of mutant ras must be confirmed by DNA sequencing. Thus, to speculate about this observation without in-depth analysis of the precise mutation present is inappropriate. The interpretation of Marangoz and Güllü that our results may suggest an explanation for why cervical epithelial cells do not invade beyond the basement membrane is interesting. The relation between the proteins we studied (p53, p62myc, and p21ras) and the ability of a cell to invade the basement membrane was not addressed in our experimental design. Thus, to include an extensive discussion of our data in regard to biopsies showing invasion (no such biopsies were included in our study) would require a consensus among investigators regarding the expression levels of ras, c-myc, and p53 in invasive lesions. Because no such consensus exists, our comment that altered expression of ras, myc, and p53 likely contributes to the development of cervical carcinoma but expression does not vary in precursor lesions is appropriate.1 Betty L. Slagle Ph.D.*, Raymond H. Kaufman M.D. , William C. Reeves M.D. , Joseph P. Icenogle Ph.D. , * Division of Molecular Virology, Baylor College of Medicine, Houston, Texas, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, Division of Viral and Rickettsial Diseases, Viral Exanthems and Herpesvirus Branch, Centers for Disease Control and Prevention, Atlanta, Georgia