Decreased expression of Ki-67 in atrophic cervical epithelium of post-menopausal women

Bulten, Johan; Wilde, P.C.M. de; Schijf, C.P.T.; Laak, J.A.W.M. van der; Wienk, S.; Poddighe, Pino J.; Hanselaar, A. G. J. M.

doi:10.1002/(sici)1096-9896(200004)190:5<545::aid-path549>3.0.co;2-s

Cited by 25 publications

(11 citation statements)

References 13 publications

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“…The Ki-67 labelling index is low in normal cases and gradually increases with CIN. [33][34][35] Ki-67 immunoreactivity has been found to be a useful and reliable proliferation marker in smears from postmenopausal women. 11 34 In our study, Ki-67 immunoreactivity was mostly positive in HSIL and carcinoma cells and negative in normal cells and LSIL, so that this marker could be used to distinguish between these two groups.…”

Section: Discussionmentioning

confidence: 99%

Chromosome in situ hybridisation, Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology

Cheung

Chiu²,

Tsun³

et al. 2004

J Clin Pathol

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Aims: To assess the potential value of chromosome in situ hybridisation (CISH), Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology to help detect carcinoma cells and precursors. Method: Sixty ThinPrep processed cervical cytology samples were studied: 23 cases within the normal limit, 13 low grade squamous intraepithelial lesions (LSILs), 10 high grade squamous intraepithelial lesions (HSILs), six squamous cell carcinomas, three endocervical adenocarcinomas, two cervical adenosquamous cell carcinomas, and three endometrial adenocarcinomas. CISH was performed with DNA probes specific for the pericentromeric regions of chromosome 11 and 16. Hybridisation signals were visualised with the streptavidin-biotin peroxidase technique. The monoclonal MIB1 and polyclonal TRT-H231 antibodies were used to detect Ki-67 and telomerase immunoreactivity, respectively. Results: Non-specific background staining was almost absent in CISH slides. Normal squamous and glandular cells showed a diploid chromosomal pattern. A relative gain in chromosomes 11 and 16 (aneusomy) was seen in HSIL and the carcinomas (p,0.0001). In MIB1 stained smears, normal cells and koilocytes showed inconspicuous immunoreactivity, whereas strongly immunoreactive nuclei were found in cancer cells and HSIL (p,0.0001). Not only carcinoma and HSIL cells, but also some normal cells, showed cytoplasmic staining for telomerase. Conclusions: These preliminary results indicate that ThinPrep processed cervical smears are suitable for CISH and immunocytochemical studies. The neoplastic squamous and glandular cells were easily identified based on nuclear aneusomy and strong Ki-67 immuoreactivity in the context of abnormal nuclear morphology. This is the first study to apply CISH in cervical cytology using an immunoenzymatic approach. C ervical cancer is one of the most common forms of cancer in women worldwide. Cytological examination of cervical smears is the most widely applied screening method for cervical cancer and its precursors. However, the success of the Papanicolaou smear test is limited with respect to sensitivity and specificity. False negative rates for cervical premalignant lesions and cervical cancer lie between 15% and 50% and false positive rates of approximately 30% have been reported.1 Such suboptimal performance may be related to the subjectivity of cytological diagnosis. ThinPrep processing, an automated cytopreparatory method, has been reported to produce good quality cervical cytology preparations. Moreover, it allows the use of auxiliary laboratory techniques, which may help to distinguish neoplastic from benign diseases, and thus may further improve the efficiency of cancer detection in cervical cytology.A wide array of immunohistochemical and molecular markers have been tested to evaluate their specificity in staining dysplastic cells in cervical smears.2-8 Immunohistochemical detection of the MIB1 (Ki-67) antigen is one of the most frequently used methods for studying cell proliferation in cancer. 9 We have shown in ea...

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Section: Discussionmentioning

confidence: 99%

Chromosome in situ hybridisation, Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology

Cheung

Chiu²,

Tsun³

et al. 2004

J Clin Pathol

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“…10 Many found Ki-67 to have prognostic and diagnostic value in the classification of CIN or as a surrogate marker for HPV related neoplasia. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] There are only a few studies that have used cytology to test whether Ki-67 could function as an adjunctive or complementary tool. Similar to the results of our present study, they report Ki-67 immunocytochemistry to be of value as a complementary tool in cervical cytology, not only in the initial triage of minor abnormalities, but also in the follow up of abnormal Pap smears.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13][14][15][16][17][18][19][20][21] Ki-67 has been used in routine cervical pathology to assess adequate excision of cervical intraepithelial neoplasia (CIN) and to differentiate between postmenopausal atrophy and CIN. 22 "In dysplasia and carcinoma, Ki-67 expression extends above the basal one third of the epithelium and the number of positive cells increases"…”

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confidence: 99%

Ki-67 immunocytochemistry in liquid based cervical cytology: useful as an adjunctive tool?

Sahebali

Depuydt²,

Segers³

et al. 2003

Journal of Clinical Pathology

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Aims: To test the ability of Ki-67 to detect cytological lesions in a screening setting and its use as a surrogate marker of human papillomavirus (HPV) infection. Methods: A study of liquid based cytology, HPV DNA testing by MY09/MY11 consensus polymerase chain reaction (PCR), type specific PCRs, and Ki-67 immunocytochemistry on a randomly selected series of 147 patients. Results: Comparison of the number of Ki-67 immunoreactive cells/1000 cells in the different cytological groups showed that the HSIL group yielded a significantly higher mean count than did the other groups. The number of Ki-67 immunoreactive cells/1000 cells was significantly higher in HPV-16 positive samples than in samples containing infections with other high risk types. Receiver operating characteristic curves indicated a test accuracy (area under curve) of 0.68, 0.72, and 0.86 for atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesions (LSIL), and high grade squamous intraepithelial lesions (HSIL), respectively. Thresholds for 95% sensitivity were 0.07, 0.08, and 0.15 Ki-67 immunopositive cells/1000 cells for ASCUS, LSIL and HSIL, respectively. The threshold for 95% specificity was 1.9 Ki-67 immunopositive cells/1000 cells. Conclusions: Ki-67 immunocytochemistry can be applied to liquid based cytology. The accuracy and diagnostic indices of the test are good when compared with those of other techniques. As part of a panel of screening procedures, it could be used as an adjunct to liquid based cytology to identify HSIL, and as a surrogate marker of HPV-16 infection.T he causal relation between genital human papillomavirus (HPV) infection and cervical dysplasia/carcinoma is well established.1-3 HPV type 16 (HPV-16) is most frequently found in cervical squamous cell carcinoma, with more than 50% of these tumours harbouring this type. 4 However, even though the prevalence of HPV infection can be as high as 60%, only 10% of infected women will develop cervical dysplasia.

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“…Moreover, the medical history of the women with HPV‐negative biopsies did not indicate different hormone use. Furthermore, it was recently shown that measuring the proliferative activity is a reliable procedure for differentiating between cervical atrophy and CIN 2/CIN 3 cases17. It thus seems unlikely that the above hypotheses are an adequate explanation for CIN lesions with SI90≤0.60.…”

Section: Discussionmentioning

confidence: 99%

Relationship between the presence of oncogenic HPV DNA assessed by polymerase chain reaction and Ki‐67 immunoquantitative features in cervical intraepithelial neoplasia

Kruse

Baak

Bruin

et al. 2001

The Journal of Pathology

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The aims of this study were firstly to determine which Ki-67 immunoquantitative parameters correlate with the presence of oncogenic human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) lesions; and secondly to compare prospectively the routinely assessed CIN grades with the Ki-67 quantitative pathological CIN grade, the expert revised grade, and the presence of oncogenic HPV DNA. HPV polymerase chain reaction (PCR) and Ki-67 immunoquantitation were performed on 90 consecutive biopsies (16 CIN 1, 35 CIN 2, and 39 CIN 3). CIN grade was assessed routinely by six different pathologists. The presence of the lesion was confirmed in a histological section following the material used for PCR and Ki-67 analysis. In a second prospective routine test set analysis, 66 more CIN lesions (14 CIN 1, 15 CIN 2, and 37 CIN 3) were routinely graded (also by six different pathologists, routine CIN grade=CIN(ROUT)), studied for oncogenic HPV DNA, and graded by quantitative Ki-67 features (quantitative pathological CIN grade=CIN(QP)). These latter cases were blindly revised by one of the authors (reference CIN grade=CIN(REF)). Eight of the nine Ki-67 immunoquantitative features showed a significant difference between the oncogenic HPV-positive and -negative cases. The best single discriminator was the 90th percentile of the stratification index (SI90). All 61 cases with Ki-67 SI90>0.60 were HPV-positive (68% of the total group studied). Of the 29 cases with SI90< or =0.60, 16 were negative and 13 positive for oncogenic HPV and none of the Ki-67 features (either single or combined) could distinguish them. Using stepwise multivariate analysis, the best discriminating combination of features was SI90 and the percentage of Ki-67-positive nuclei in the deep third layer of the epithelium (PERC DL). The combination of SI90 and the percentage of Ki-67-positive nuclei per 100 microm basal membrane was nearly as strong as that of SI90 and PERC DL. With these two features, 86% of the cases were correctly classified. The subjective estimate of SI90 (>0.60 or < or =0.60) by two independent observers was not accurate and not reproducible. In the prospective routine test set analysis of 66 cases, the 37 CIN(ROUT)=3 all had CIN(QP) and CIN(REF)=3 and all these cases were oncogenic HPV-positive. Eight of the 14 original CIN(ROUT)=1 grades were oncogenic HPV (=HPV)-positive and five of these eight were upgraded by CIN(QP) to CIN 2 and CIN 3. These upgrades were in agreement with the blind reference revisions. The six HPV-negative CIN(ROUT)=1 cases were CIN 1 both by CIN(QP) and by CIN(REF). Thirteen of the 15 original CIN(ROUT)=2 grades were HPV-positive and seven of these were CIN(QP)=3. All six HPV-positive CIN(ROUT)=2 cases that were CIN(QP)=2 were also CIN(REF)=2 at blind revision. In conclusion, this study has shown firstly, that in CIN lesions, Ki-67 immunoquantitative features and the presence of oncogenic HPV are highly correlated, and also within one subjective CIN grade; secondly, that subjective impressions of SI90 are not a...

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Decreased expression of Ki-67 in atrophic cervical epithelium of post-menopausal women

Cited by 25 publications

References 13 publications

Chromosome in situ hybridisation, Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology

Chromosome in situ hybridisation, Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology

Ki-67 immunocytochemistry in liquid based cervical cytology: useful as an adjunctive tool?

Relationship between the presence of oncogenic HPV DNA assessed by polymerase chain reaction and Ki‐67 immunoquantitative features in cervical intraepithelial neoplasia

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