Difference of Genome-Wide Copy Number Alterations between High-Grade Squamous Intraepithelial Lesions and Squamous Cell Carcinomas of the Uterine Cervix

BACKGROUND: About 10% of high-grade squamous intraepithelial lesions (HSILs) progress to invasive carcinomas within 2-10 years. By delineating the events that occur in the early stage of the invasion, the pathogenesis of cervical cancer could be better understood. This will also propose the possible methods for inhibiting the tumor invasion and improving the survival of patients. METHODS: We compared the genomic profiles between the HSIL and the invasive squamous cell carcinoma (SCC) using an array comparative genomic hybridization. Using recurrently altered genes, we performed a principal component analysis to see variation of samples in both groups. To find possibly affected pathways by altered genes, we analyzed genomic profiles with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database and GOEAST software. RESULTS: We found 11q12.3 and 2p24.1 regions have recurrent copy number gains in both groups. 16p12-13 and 20q11-13 regions showed an increased copy number only in cases of HSIL. 1q25.3 and 3q23-29 regions showed copy number gains only in cases of SCC. Altered genes in the SCC group were related to the mitogen-activated protein kinase signaling pathway and the RNA transport. Altered genes in the HSIL group were related to the ubiquitin mediated proteolysis and cell adhesion molecules. CONCLUSIONS: Our results showed not only that gains in 11q12.3 and 2p24.1 were early events occurring in the premalignant lesions and then maintained in cases of SCC but also that gains in 1q25.3 and 3q23-29 were late events occurring after invasion in those of SCC.

Copy Number Alterations of BCAS1 in Squamous Cell Carcinomas

BACKGROUND: Breast carcinoma amplified sequence 1 (BCAS1), located in 20q13, is amplified and overexpressed in breast cancers. Even though BCAS1 is expected to be an oncogene candidate, its contribution to tumorigenesis and copy number status in other malignancies is not reported. To elucidate the role of BCAS1 in squamous cell carcinomas, we investigated the copy number status and expression level of BCAS1 in several squamous cell carcinoma cell lines, normal keratinocytes and primary tumors. METHODS: We quantitated BCAS1 gene by real-time polymerase chain reaction (PCR). Expression level of BCAS1 was measured by real-time reverse transcription-PCR and immunoblot. RESULTS: Seven (88%) of 8 squamous cell carcinoma cell lines showed copy number gain of BCAS1 with various degrees. BCAS1 gene in primary tumors (73%) also showed copy number gain. However, expression level did not show a linear correlation with copy number changes. CONCLUSIONS: We identified copy number gain of BCAS1 in squamous cell carcinomas. Due to lack of linear correlation between copy numbers of BCAS1 and its expression level, we could not confirm that the overexpression of BCAS1 is a common finding in squamous cell carcinoma cell lines. However, this study shows that the copy number gain of BCAS1 is a common finding in squamous cell carcinomas.

Prognostic significance of syndecan-1 expression in cervical cancers / 부인종양

OBJECTIVE: Syndecans are reported to have variable expression in several solid tumors and blood cancers. The cause provoking altered expression of syndecans is not known to date. We studied copy number status of syndecan-1 (SDC1) and significance of SDC1 gene product (syndecan-1, SDC1) expression in cervical cancers. METHODS: Using 121 cases of cervical cancer tissues, we screened SDC1 expression pattern using immunohistochemistry. We analyzed the relationship between SDC1 expression and clinicopathological parameters. To find possible causes of the expression change, we exploited interphase fluorescent in situ hybridization to screen copy number alteration of SDC1. RESULTS: Among 121 cases, 101 (83.5%) were positive and 20 (16.4%) were negative for SDC1. Among the parameters, age, histological type, and grade were significantly associated with SDC1 expression (p<0.05). Strong SDC1 expression in the cytoplasm showed better patient survival (p=0.02). In multivariate regression model, grade and SDC1 expression were independent prognostic factors (p<0.05). SDC1 in cervical cancers did not show copy number alteration. CONCLUSION: Strong SDC1 expression in the cytoplasm of tumor cells predicts better patient survival. The change of SDC1 expression in cervical cancers is not caused by copy number alteration of the gene.