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...
P63 and p73 are two homologues of the important tumor suppressor gene p53. In this study, we investigated p63 and p73 expression by immunocytochemistry using antibodies for TAp73 and p634A4 isoforms in 91 highgrade and 107 low-grade squamous intraepithelial lesions, 212 atypical squamous cells of undetermined significance, 9 squamous cell carcinomas and 63 normal samples from an Asian screening population together with 47 hospital samples of carcinomas. There was significant correlation between the TAp73 and p634A4 indices (Po0.0001). Significantly, higher TAp73 and p634A4 indices were found in high-grade lesions or carcinoma when compared with atypical squamous cells and low-grade lesions (Po0.0001). Among atypical squamous cells, p634A4 indices of cases that subsequently progressed to low-grade (P ¼ 0.031) or high-grade lesions (P ¼ 0.006) were significantly higher than those that did not. For atypical squamous cells positive for high-risk human papillomavirus (HPV) as detected by Digene (61%), cases with high p634A4 index were still more likely to have subsequent high-grade lesions detected (P ¼ 0.016). Among low-grade lesions, significantly higher TAp73 (P ¼ 0.038) was found in cases that subsequently progressed to high-grade lesions. There was significant correlation between presence of high-risk HPV and p634A4 index (P ¼ 0.01). In summary, p63 and p73 immunocytochemistry are potential good markers for detection of carcinoma and high-grade lesions in cervical cytology samples and for triage management of women with atypical squamous cells and low-grade Cervical cytology screening is effective in the prevention of cervical cancer by detecting asymptomatic cervical cancer and its precursors although there is limitation in its sensitivity and specificity. 1 Among cytological abnormalities detectable in a screening population, atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL), especially the former, are the most common diagnostic categories. [2][3][4] Both were associated with a higher possibility of subsequent development of cervical cancer when compared with women with negative cytology. 3 Colposcopic examination of all such cases poses significant demand on the community resources. To improve the efficiency of cervical cancer screening, human papillomaviruses (HPV) DNA testing has been introduced for the triage of women with ASC-US and for primary screening. 5,6 Although HPV test shows high sensitivity, additional markers are necessary to improve the specificity of identifying cervical cancers or high-grade precursors. [7][8][9][10][11] It is also necessary to discover adjunct markers for management of LSIL as HPV testing is not so effective in triage management of LSIL.
Iread with some interest the report by Cheung et al. 1 comparing the diagnostic results obtained using the ThinPrep test (Cytyc Corp., Boxborough, MA) with the results obtained using conventional cervical cytologic methods. The authors noted that the incidence of high-grade squamous intraepithelial or more severe lesions was not significantly increased among women for whom the ThinPrep test was performed. In fact, fewer cases of high-grade squamous intraepithelial or more severe lesions were detected during the 2-year period in which the ThinPrep test was performed compared with the period in which conventional methods were used (469 of 190,667 [0.246%] vs. 508 of 191,581 [0.265%]). Nonetheless, diagnoses of atypical squamous cells of undetermined significance, atypical glandular cells of undetermined significance, and low-grade squamous intraepithelial lesions all increased, and the authors considered this finding to be indicative of a significant enhancement in efficiency relative to cervical cytologic screening. Assuming that the two populations examined actually were identical and that cytologic interpretations of the cells present were equally accurate, one would be forced to conclude that some high-grade lesions were not adequately detected by the ThinPrep technique. REFERENCE1. Cheung AN, Szeto EF, Leung BS, Khoo US, Ng AW. Liquid-based cytology and conventional cervical smears: a comparison study in an Asian screening population. Cancer. 2003;99:331-335.
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