Identification of progressive cervical epithelial cell abnormalities using DNA image cytometry

Abstract

BACKGROUND The objectives of the current study were to compare the capabilities of conventional cervical cytology and of DNA image cytometry (DNA‐ICM) in the prediction of progressive or regressive behavior in atypical squamous cells (ASC), low‐grade squamous intraepithelial lesions (LSIL), and atypical glandular cells (AGC). METHODS One hundred ninety‐six women with Papanicolaou (Pap) smears that yielded diagnoses of ASC, LSIL, or AGC were included in a prospective cohort study. Slides were classified according to the Bethesda system. DNA‐ICM was performed according to the consensus reports of the European Society of Analytical Cellular Pathology. RESULTS Reference standard verification was available in 108 patients. The rate of DNA aneuploidy in Pap smears increased significantly from cervical intraepithelial neoplasia 1 (CIN1) (54%) and CIN2 (64.3%) to CIN3 or greater (CIN3+) (83.3%) in subsequent biopsies (P < 0.05). Using ASC, LSIL, and AGC as input cytologic diagnoses and ≥ CIN2 as the output histologic diagnosis, the positive predictive values (PPVs) for conventional cytology and DNA‐ICM were 35.2% and 65.9%, respectively (P < 0.001). The negative predictive value (NPV) of DNA‐ICM was 85.0%. When ≥ CIN3 was used as the output histologic diagnosis, conventional cytology had a PPV of 22.2%. The PPV and NPV of DNA‐ICM were 43.9% and 93.3%, respectively. CONCLUSIONS The results of the current study confirmed the prognostic validity of DNA image cytometry for differentiation between progressive and regressive lesions in patients with ASC, LSIL, and AGC diagnoses. Cancer (Cancer Cytopathol) 2004. © 2004 American Cancer Society

Gene Expression Analysis of Preinvasive and Invasive Cervical Squamous Cell Carcinomas Identifies HOXC10 as a Key Mediator of Invasion

“…This is not necessarily surprising, given that HSILs and invasive carcinomas share many morphologic and molecular characteristics. Like invasive cervical carcinomas, HSILs are clonal, frequently aneuploid, and often harbor integrated HPV DNA (9,(29)(30)(31)(32). One recent study that used DNA microarray data to identify chromosomal copy number alterations in preinvasive and invasive cervical carcinomas showed gains of chromosomes 12q and losses of 12p in both types of lesions (33).…”

Biomarkers of Cervical Dysplasia and Carcinoma

“…Subsequent studies have reported a strong association between highly aneuploid squamous cells and HR-HPV [62] as well as a positive predictive value of 81.8% for CIN 2 for 9c cells [63]. A prospective study by Grote et al demonstrated a significant increase in DNA aneuploidy in cervical cytology material from patients with CIN 1 (54%) and CIN 2 (64.3%) to CIN 3 or greater (83.3%) on subsequent biopsies [64]. In a preliminary retrospective study assessing the utility of DNA ploidy in the management of ASC cytology specimens, Lorenzato et al suggest that the combined use of HR-HPV testing and DNA ploidy measurement on ASCUS cytology specimens may improve the triage of women who have to undergo colposcopy as well as identify patients with a diagnosis of ASC-H at higher risk for CIN 2 or greater lesions [65].…”

Aneuploidy Approaching a Perfect Score in Predicting and Preventing Cancer: Highlights from a Conference Held in Oakland, CA in January, 2004

“…The median interval between the initial "atypical" smear and the subsequent histological grading into "cervical intraepithelial neoplasia (CIN) status I-III" was 3 months. 53 During this interval 65% of the aneuploid atypical samples, but only 35% of the total atypical samples developed a neoplastic status of > CIN II. Moreover, "DNA image cytology" correctly predicted that the majority of diploid or near diploid atypical samples did not progress to a neoplastic state, "non-progression within 6 months was 85%".…”