Clonality analysis of archival cervical smears. Correlation of monoclonality with grade and clinical behavior of cervical intraepithelial neoplasia.
OBJECTIVE
To establish a polymerase chain reaction (PCR)-based clonality assay for archival cervical smears and examine its value in the detection of cervical intraepithelial neoplasia (CIN) and prediction of its clinical behavior.


METHODS
Dyskaryotic cells were microdissected from archival cervical smears of 33 cases and subjected to PCR-based clonality analysis of the androgen receptor gene. High-risk HPV subtypes were screened by PCR.


RESULTS
Monoclonal patterns were found in 9/9 CIN 3 and 15/21 CIN 2, while polyclonal patterns were observed in the remaining 6 CIN 2 and 3/3 CIN 1. All patients with monoclonal CIN lesions, including 15 CIN 2, showed recurrence of the disease despite treatment. The original CIN 2 and recurrent CIN lesion in each of the 6 examined cases showed the same monoclonal pattern, suggesting a clonal link. In contrast, the patients with polyclonal CIN 1 or 2 became negative and remained disease free. High-risk HPV subtypes were found in all monoclonal CIN lesions, including 9 CIN 3 and 15 CIN 2, and in 4/6 polyclonal CIN 2 but not in CIN 1 lesions.


CONCLUSIONS
Clonality analysis of cervical smears is potentially valuable in the identification of true neoplastic cells and prediction of clinical behavior of CIN 2 lesions.
el Hamidi
Amina
A
Department of Histopathology, University College London, Rockefeller Building, University Street, London WC1E 6JJ, U.K.
Kocjan
Gabrijela
G
Du
Ming-Qing
MQ
D001109:Archives; D014408:Biomarkers, Tumor / Q000235:genetics; D002999:Clone Cells / Q000473:pathology; D020732:Cytogenetic Analysis; D004247:DNA / Q000032:analysis / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D027383:Papillomaviridae / Q000235:genetics; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D011944:Receptors, Androgen / Q000235:genetics*; D013997:Time Factors; D014626:Vaginal Smears / Q000379:methods* / Q000639:trends; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology*
D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D004247:DNA