Role of chromosome 3q26 gain in predicting progression of cervical dysplasia.

OBJECTIVE: This study aimed to determine whether 3q26 gain can predict which low-grade squamous intraepithelial lesions (LSILs) and atypical squamous cells of undetermined significance (ASCUSs) will progress to higher-grade squamous intraepithelial lesion (HSIL). METHODS: Liquid cytology specimens of LSIL and ASCUS from 73 women were examined using fluorescent in situ hybridization (FISH) for the detection of 3q26 gain. All women underwent colposcopy and biopsy at the initial visit and 40 of them with histology showing cervical intraepithelial neoplasia 1 (CIN 1) or human papillomavirus infection (koilocytosis) were included in the study. They were reevaluated with liquid cytology, colposcopy, and biopsy after a median follow-up of 17.5 months. RESULTS: A total of 40 cases were analyzed (31 LSILs and 9 ASCUSs). Of these cases, 8 (20%; 6 LSILs and 2 ASCUSs) were positive and 32 (80%) were negative for 3q26 gain according to FISH. Three of the 8 positive women (38%) progressed to HSIL/CIN 2 or worse, whereas none of the 32 negative women did so. 3q26 gain could predict progression with a negative predictive value of 100% (95% confidence interval, 89.1%-100%). In addition, women positive for 3q26 gain had a significantly lower regression rate compared with negative women (P = 0.009). CONCLUSIONS: In this first prospective study, 3q26 gain in LSIL/ASCUS cytology exhibited an impressive negative predictive value for progression to HSIL/CIN 2 or worse. Thus, 3q26 gain may be useful in stratifying patients' risk for progression and possibly alter management and reduce cost of follow-up.

Gain of 3q26: a genetic marker in low-grade squamous intraepithelial lesions (LSIL) of the uterine cervix.

OBJECTIVE: Physicians have few resources for determining which LSIL will progress to HSIL or regress. Recently the chromosome 3q26 region was found to be amplified in patients with cervical cancer. The frequency of this 3q gain increased with severity of dysplasia. The primary objective of this study was to evaluate an automated FISH assay for detection of 3q gain in liquid cytology samples as a potential tool for risk stratification and triaging. METHODS: Slides prepared from 257 liquid cytology specimens (97 Negative, 135 LSIL 25 HSIL) were hybridized with a single-copy probe for the chromosome 3q26 region and a probe for the centromeric alpha-repeat sequence of chromosome 7, using standard FISH methods. Using automated analysis, the total number of nuclei and the number of nuclei with >2 signals for 3q26 were determined, using a 20x objective. The nuclei were rank ordered based on number of 3q26 FISH signals. The 800 nuclei with the highest number of signals were scored using both FISH probes and nuclei with increased numbers of 3q signals were enumerated. RESULTS AND CONCLUSIONS: Analysis of 257 specimens demonstrated that a fully automated FISH scoring system can detect 3q gain in liquid cytology samples. A fully automated method for determination of 3q gain in liquid cytology may be the assay necessary to implement routine testing. Additional studies to validate the utility of this technology are needed.

Increasing diagnostic accuracy with a cell block preparation from thin-layer endometrial cytology: a feasibility study.

OBJECTIVE: To investigate (1) the feasibility of preparing cell blocks by inverted filter sedimentation (IFS-CB) from endometrial samplings processed by the ThinPrep (TP) technique (Cytyc Corp., Boxborough, Massachusetts, U.S.A.), and (2) the possibility of increasing the diagnostic accuracy of TP endometrial cytology by examining the tissue architecture as an adjunctive method of detecting endometrial lesions. STUDY DESIGN: Three hundred one endometrial samplings were obtained, using the Endogyn endometrial device (Biogyn S. n.c., Italy), from perimenopausal and postmenopausal women. The endometrial samplings were collected in a vial with liquid fixative for the TP processing. One TP slide was prepared from each case. If adequate material remained in the vial after the TP slide preparation, it was processed for IFS-CB preparation. RESULTS: IFS-CB preparation was processed in 263 cases (87%) with adequate material. Diagnoses on IFS-CB preparations obtained by endometrial sampling matched those of the hysterectomy specimens. The addition of IFS-CB histology to the cytologic diagnosis by TP increased the diagnostic accuracy of endometrial cytology to 96.3% and 100% for benign/atrophic endometrium and adenocarcinoma, respectively (p = 0.39 and 0.46). In hyperplasia without atypia and hyperplasia with atypia, the diagnostic accuracy increased significantly, to 96% and 95.3%, respectively (p = 0.037 and < 0.001). CONCLUSION: This study illustrates the merit of linking TP cytology with direct endometrial sampling, including small tissue fragments and material adequate for IFS-CB preparation. TP cytology provides an accurate cytologic diagnosis and the possibility of IFS-CB preparation, which could be a valuable diagnostic adjunct to TP cytology.

Study on the morphology and reproducibility of the diagnosis of endometrial lesions utilizing liquid-based cytology.

BACKGROUND: The objective of the current study was to determine the diagnostic cytomorphologic criteria for liquid-based cytology and to evaluate the reproducibility and usefulness of the cytologic diagnosis in endometrial lesions. METHODS: A total of 162 direct endometrial samplings taken from postmenopausal women were evaluated by 2 skilled cytopathologists in endometrial cytology. The cytologic diagnosis was made according to the 1994 classification scheme of the World Health Organization. After establishment of the criteria, three additional cytopathologists without any experience in liquid-based endometrial cytology examined the same cases to determine interobserver variability. The intraobserver variability also was evaluated by all the observers. RESULTS: The cytomorphologic criteria were established in the following four diagnostic categories: atrophic endometrium, hyperplasia without atypia, hyperplasia with atypia, and adenocarcinoma. The overall interobserver agreement was nearly perfect with a kappa value of 0.89 during the checking round and ranged from moderate to substantial with kappa values of 0.48-0.80, respectively, in the other diagnostic rounds (P < 0.0001); hyperplasia with atypia was found to be the most difficult category to identify correctly. Furthermore, the intraobserver agreement ranged from substantial to perfect with kappa values of 0.61-1.00 in all diagnostic rounds (P < 0.0001). CONCLUSIONS: Liquid-based cytology allows for standardized and reproducible endometrial preparations, which in turn allows the application of common diagnostic criteria among cytopathologists. Furthermore, liquid-based cytology in combination with endometrial sampling could be a useful tool for the outpatient diagnosis of endometrial lesions, which could reduce unnecessary curettage.