Connective tissue activating peptide III expression disappears progressively with increased dysplasia in human cervical epithelium

Objective. The aim of this study was to explore the possible involvement of CTAP-III in the development of cervical cancer as it progresses through se veral cervical intraepithelial neoplasia (CIN) stages. Material and methods. Twenty-four cervical specimens were obtained by direc t punch biopsy, conization, or hysterectomy. Diagnosis of CIN I to CIN III was based on standard morphological criteria in 12 specimens. Tissue specim ens were also obtained from 4 normal uteri and 8 cases of invasive squamous cell cervical carcinoma. RT-PCR, using CTAP-III-specific primers, was used to identify CTAP-III mRNA and polyclonal antibodies, directed against the N-terminus of CTAP-III, for immunostaining of the CTAP-III protein. Results. RT-PCR yielded amplified fragments in RNA derived from normal cerv ical tissue, while no PCR product was detected in the invasive cervical car cinoma tissue. The PCR product corresponded to a CTAP-III plasmid PCR produ ct. Both tissues expressed the same amounts of GAPDH mRNA as the control fo r the integrity and equal amounts of the isolated RNA. In each of the 16 sp ecimens of normal cervices and of CIN tissues, epithelial cells were staine d with the anti-CTAP-III antibodies. In normal epithelium, CTAP-III stainin g was homogeneously distributed in all epithelial layers, except in the hig hly active and proliferating basal cells. CTAP-III was localized at the epi thelial eel membrane or between adjacent epithelial cells in a granular, ch ain-like pattern of staining. In the CIN specimens, CTAP-III staining was n o longer seen in the deep epithelial layers, consistent with the dysplastic appearance of the cells, and remained in the seemingly normal superficial epithelial layers. Cells of invasive cervical carcinoma did not stain for C TAP-III and were detected in endothelial cells of capillary blood vessels. Conclusion. The specific localization of CTAP-III between adjacent epitheli al cells suggests a possible role of this chemokine in maintaining the norm al architecture of epithelial tissues. Its progressive disappearance in inc reasingly severe CIN may be applied to distinguish between specific stages in the progression of cervical carcinoma. (C) 2000 Academic Press.