METHODOLOGY: MCM2, 4, 5 and 7 genes expression profiles were evaluated in three cervical tissue samples each of normal cervix, human papillomavirus (HPV)-infected low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC), using Human Transcriptome Array 2.0 and validated by nCounter® PanCancer Pathway NanoString Array. Immunohistochemical expression of MCM2 protein was semi-quantitatively assessed by histoscore in tissue microarrays containing 9 cases of normal cervix, 10 LSIL, 10 HSIL and 42 cases of SCC.
RESULTS: MCM2, 4, 5 and 7 genes expressions were upregulated with increasing fold change during the progression from LSIL to HSIL and the highest in SCC. MCM2 gene had the highest fold change in SCC compared to normal cervix. Immunohistochemically, MCM2 protein was localised in the nuclei of basal cells of normal cervical epithelium and dysplastic-neoplastic cells of CIN and SCC. There was a significant difference in MCM2 protein expression between the histological groups (P = 0.039), and histoscore was the highest in HSIL compared to normal cervix (P = 0.010).
CONCLUSION: The upregulation of MCM genes expressions in cervical carcinogenesis reaffirms MCM as a proliferative marker in DNA replication pathway, whereby proliferation of dysplastic and cancer cells become increasingly dysregulated and uncontrolled. A strong expression of MCM2 protein in HSIL may aid as a concatenated screening tool in detecting pre-cancerous cervical lesions.
METHODOLOGY: A retrospective study was conducted to evaluate 77 cervical cases collected from the histopathology laboratory of Ipoh hospital from 1st January, 2005, to 31st December, 2006.
RESULTS: Cervical intraepithelial neoplasia (CIN) was found in 33 (42%) cases, CIN III accounting for 27%, and CIN I, CIN II and CIN II-III 5% each. The highest rate for CIN cases was 43% in the 41-50 year age group and the lowest rate was 6% in the group aged 61-70 years. Non-keratinizing and metastatic squamous cell carcinomas (SCCs) accounted for 16% and 13%, respectively, the combination being second in majority (29%), followed by adenocarcinoma (17%). The histopathological results showed CIN I to be characterized by mild papillary projections of the epithelium with some degree of nuclear enlargement, pleomorphism, mild koilocytosis, bionucleated cells and a low nucleo-cytoplasmic ratio. CIN II demonstrated typical squamous epithelium with disorganization of the lower part of the epithelium accompanied by nuclear hyperchromatism, an increased nucleo-cytoplasmic ratio, and scanty mitotic figures. CIN III was characterized by pleomorphic nuclei, atypical cells with mitotic figures, nucleo-cytoplasmic ratio, anisokaryosis and hyperchromasia.
CONCLUSION: Lesions related to cervical cancer showed tumor progression correlating with histopathological changes in cell morphology.
METHODS: Liquid based cervico-vaginal cytology specimens with squamous abnormalities and corresponding histology from 97 women with subsequent colposcopy and biopsy were included. The specimens were then subjected to the dual stain and Roche Cobas 4800 multiplex real time PCR HPV DNA testing. The sensitivity and specificity of the dual stain and HPV testing were calculated using CIN 2+ on histology as a reference standard.
RESULTS: The sensitivity and specificity of the dual stain in detecting histology proven CIN 2+ was 93.7% and 76.5% while HPV testing was 85.7% and 14.7% respectively. Of the 44 women with ASCUS or LSIL on cytology, the dual stain also reduced the number of unnecessary colposcopy referrals from 27 to 7 when used as a triage marker compared to HPV testing.
CONCLUSION: p16/Ki-67 dual stain was more sensitive and specific than HPV testing in determining the presence of CIN 2+ on histology. It could triage low grade cervico-vaginal specimens more effectively and potentially help women avoid unnecessary colposcopies. Future studies are needed to further evaluate its role in cervical cancer screening programmes.