Semi-automated diagnosis of cervical intra-epithelial neoplasia grade 2 by the measurement of acid labile DNA in cytologically normal nucle

Sincock, A. M.

doi:10.1002/1097-0142(19860701)58:1<83::aid-cncr2820580115>3.0.co;2-j

Cited by 9 publications

(3 citation statements)

References 16 publications

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“…Looking at the hydrolysis curves in our cases, it becomes clear that the increase of hydrolyzed DNA in nuclei from benign urothelium is delayed compared with that of malignant tumor cell nuclei. This has been reported to be a constant finding in various tissues investigated 13–19. In our cases, this early increase was even more pronounced in the more aggressive tumors ( P = 0.001; data not shown).…”

Section: Discussionsupporting

confidence: 76%

“…In contrast to determining DNA ploidy, other studies have investigated the dynamics of the Feulgen hydrolysis reaction, which differentiates a rapidly hydrolyzed component of nuclear DNA, the increase of which is linked to malignancy 13–15. Semiautomated, quantitative determination of acid‐labile DNA has been applied successfully applied to cervical smears to detect cervical intraepithelial neoplasia 16–19. We measured the rapidly hydrolyzable fraction of DNA from patients with normal urothelium and with urothelial tumors to determine whether sufficient discrimination can be achieved between these groups for the purpose of monitoring patients with carcinoma of the bladder and bladder carcinoma screening.…”

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Quantitative assessment of bladder carcinoma by acid labile DNA assay

Gschwendtner

Mairinger

1999

Cancer

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BACKGROUND Effective noninvasive methods for monitoring patients with bladder carcinoma and screening for bladder carcinoma that show better performance than the methods currently in use would be desirable for detecting urothelial carcinoma at an early, easily treatable stage. A rapidly hydrolyzed component of nuclear DNA has been described, the increase of which has been linked to malignancy. Quantitative determination of acid labile DNA has been applied successfully to detect other neoplasms. This study investigates the potential of this method to detect transitional cell carcinomas. METHODS Touch imprints of transurethral resection material from 62 cases of nonmalignant urothelium (control group including reactive changes) and 94 cases of bladder carcinoma were analyzed. The full Feulgen hydrolysis profiles of the nonmalignant and malignant urothelial cells were compared by measuring the staining density of the nuclei using digital image analysis after various hydrolysis times. Twenty cells were sampled randomly from among the cells measured for calculation of the mean optical density (MOD). The MOD of each time was used to build the hydrolysis profile of a case. RESULTS A hydrolysis time of 10 minutes was found to be the most discriminative between control and carcinoma cases. Applying a single threshold MOD value of 101 resulted in a test sensitivity of 95.7%, a specificity of 94.4%, a positive predictive value of 98.3%, a negative predictive value of 95.9%, and an area under the receiver operating characteristic curve of 0.97. CONCLUSIONS The results of this pilot study suggest that measurement of the rapidly hydrolyzed component of DNA present in the nuclei of bladder urothelium offers a highly sensitive and reliable supplement to the qualitative and subjective cytologic procedures currently in use. Cancer 1999;86:105–13. © 1999 American Cancer Society.

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Section: Discussionsupporting

confidence: 76%

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confidence: 99%

Quantitative assessment of bladder carcinoma by acid labile DNA assay

Gschwendtner

Mairinger

1999

Cancer

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“…Precancerous lesions of the uterine cervix show cytogenetic aneuploidy28 as a marker of transition into aneuploid carcinomas 29–31. This aneuploidy has been demonstrated with cytometric methods as well 7–9, 12, 16, 17, 23–25, 27, 32–69. DNA aneuploidy has been regarded as an objective marker for progressive CIN 7, 33, 60.…”

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confidence: 99%

DNA cytometry confirms the utility of the Bethesda system for the classification of Papanicolaou smears

Bollmann¹,

Bollmann²,

Henson

et al. 2001

Cancer

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BACKGROUND Developed in 1989, the Bethesda System has largely replaced previous classifications of Papanicolaou (Pap) smears from the uterine cervix. The system is binary, dividing smears into two groups — low‐grade, squamous, epithelial lesions (LSIL) or high‐grade, squamous, epithelial lesions (HSIL). A third category, atypical squamous cells of undetermined significance (ASCUS), is used to classify minimal cellular changes that do not satisfy the criteria for the low‐ or high‐grade categories. This study was designed to confirm the utility of this binary division and to compare the results with another classification system (the Munich II Nomenclature) that is not binary but contains three divisions or grades for dysplasia — low, intermediate, and high. METHODS Pap smears were obtained from 593 women with a cytologic diagnosis of dysplasia based on the Munich System. Smears were then classified by the Bethesda System into LSIL or HSIL. Patients were followed for 2 years either with biopsy or repeat cytology. The initial smears were restained by the Feulgen method, and ploidy was evaluated by interactive DNA cytometry. RESULTS Of 241 cases of LSIL, 39% were diploid, 57% polyploid, and 4% aneuploid. Of 352 cases classified HSIL, 4% were diploid, 17% polyploid, and 79% aneuploid. After 2 years of follow‐up, 2 of 108 patients who were biopsied and who were originally classified as diploid progressed to cervical intraepithelial neoplasia/carcinoma in situ (CIN/CIS) whereas 109 of 217 patients who were aneuploid and biopsied were found to have CINIII/CIS. CONCLUSIONS The two divisions of the Bethesda System, LSIL and HSIL, correlated with ploidy as evaluated by cytometry. Aneuploidy was found to be useful to separate cases of HSIL from those of LSIL as defined in the Bethesda System. Because of the binary division, use of a system with three divisions for dysplasia, such as the Munich II Nomenclature, creates a therapeutic dilemma because a single diagnostic category (usually the intermediate grade) may contain both self‐limiting and progressive lesions. DNA cytometry of Pap smears was found to be useful as a routine procedure. Cancer (Cancer Cytopathol) 2001;93:222–228. © 2001 American Cancer Society.

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DNA quantification in cervical intraepithelial neoplasia thick tissue sections by confocal laser scanning microscopy

Crist¹,

Kim²,

Goldblatt³

et al. 1996

J. Cell. Biochem.

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Image analysis of tissue biopsies for determination of DNA content as an early marker of neoplasia is hampered by the complexity of corrections necessary to deal with nuclear truncation and overlap in thin sectlons. The use of confocal laser scanning microscopy (CLSM) for measurement of cellular DNAcontent on whole cells within thick tissue sections offers the advantage of preservation of cellular architecture, capacity for 3-dimensional analysis, and absence of sectioning artifacts. We have applied this technique to pararosaniline-Feulgen stained human cervical tissues graded from normal to cervical intraepithelial neoplasia (CIN) Ill. For the purpose of Comparison, 15 pm sections were stained and mapped so that the same cell population could be analyzed by both integrated optical density and fluorescence intensity. Distribution of DNA content from normal cervical epithelial cells 2-3 layers out from the basal cell layer measured by both methodologies showed a stable GO/C1 population with no observable S-phase or G2 cells. Cells measured from areas of increasing CIN grade showed progressively higher DNA content values that were not observable in normal tissue. Although these data are preliminary they suggest that CLSM can be used to identify aneuploid states within defined structural areas of pre-invasive neoplasia.

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Semi-automated diagnosis of cervical intra-epithelial neoplasia grade 2 by the measurement of acid labile DNA in cytologically normal nucle

Cited by 9 publications

References 16 publications

Quantitative assessment of bladder carcinoma by acid labile DNA assay

Quantitative assessment of bladder carcinoma by acid labile DNA assay

DNA cytometry confirms the utility of the Bethesda system for the classification of Papanicolaou smears

DNA quantification in cervical intraepithelial neoplasia thick tissue sections by confocal laser scanning microscopy

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