MAD2 and CDC20 are upregulated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix

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Abstract

Abnormal expression of the spindle assembly checkpoint proteins causes tumor cell aneuploidy, which has been reported in various malignancies. The expression of mitotic arrest deficient 2 (MAD2) and cell-division cycle 20 homolog (CDC20), the key spindle assembly checkpoint proteins, has not been studied in cervical carcinogenesis. In this study, we compared the expression of MAD2 and CDC20 in 332 cases, including normal cervical tissues, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and invasive squamous cell carcinomas (SCCs). Both MAD2 and CDC20 were overexpressed in the nuclei or cytoplasm of dysplastic and malignant tumor cells. The frequency of MAD2 overexpression was markedly increased from undetectable (0/100) in normal cervical tissues and 2% (1/50) in low-grade squamous intraepithelial lesions to 67.1% (53/79) in HSILs and 52.4% (54/103) in SCCs. Similarly, CDC20 was overexpressed in 49.4% (39/79) of HSILs and 22.3% (23/103) of SCCs, whereas CDC20 was not detectable (0/100) in normal cervical tissues and overexpressed only in 8.0% (4/50) of low-grade squamous intraepithelial lesions. In SCC cases, MAD2 overexpression correlated with a patient age of less than 60 yr (P=0.043), nonkeratinizing histologic type (P=0.018), and a lesser degree of stromal invasion (P=0.026). In conclusion, MAD2 and CDC20 overexpression was increased in HSILs and SCCs, suggesting their involvement in the initiation of cervical cancers. Controlling CDC20 and MAD2 expression may be a therapeutic strategy for cervical cancer.

Original languageEnglish
Pages (from-to)517-523
Number of pages7
JournalInternational Journal of Gynecological Pathology
Volume33
Issue number5
DOIs
Publication statusPublished - 2014 Jan 1

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Cervix Uteri
Squamous Cell Carcinoma
Cell Cycle
M Phase Cell Cycle Checkpoints
Uterine Cervical Neoplasms
Neoplasms
Aneuploidy
Squamous Intraepithelial Lesions of the Cervix
Carcinogenesis
Cytoplasm
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Obstetrics and Gynaecology

Cite this

@article{98abc5231bfa4d7ebf40166b7dfdfb26,
title = "MAD2 and CDC20 are upregulated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix",
abstract = "Abnormal expression of the spindle assembly checkpoint proteins causes tumor cell aneuploidy, which has been reported in various malignancies. The expression of mitotic arrest deficient 2 (MAD2) and cell-division cycle 20 homolog (CDC20), the key spindle assembly checkpoint proteins, has not been studied in cervical carcinogenesis. In this study, we compared the expression of MAD2 and CDC20 in 332 cases, including normal cervical tissues, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and invasive squamous cell carcinomas (SCCs). Both MAD2 and CDC20 were overexpressed in the nuclei or cytoplasm of dysplastic and malignant tumor cells. The frequency of MAD2 overexpression was markedly increased from undetectable (0/100) in normal cervical tissues and 2{\%} (1/50) in low-grade squamous intraepithelial lesions to 67.1{\%} (53/79) in HSILs and 52.4{\%} (54/103) in SCCs. Similarly, CDC20 was overexpressed in 49.4{\%} (39/79) of HSILs and 22.3{\%} (23/103) of SCCs, whereas CDC20 was not detectable (0/100) in normal cervical tissues and overexpressed only in 8.0{\%} (4/50) of low-grade squamous intraepithelial lesions. In SCC cases, MAD2 overexpression correlated with a patient age of less than 60 yr (P=0.043), nonkeratinizing histologic type (P=0.018), and a lesser degree of stromal invasion (P=0.026). In conclusion, MAD2 and CDC20 overexpression was increased in HSILs and SCCs, suggesting their involvement in the initiation of cervical cancers. Controlling CDC20 and MAD2 expression may be a therapeutic strategy for cervical cancer.",
keywords = "CDC20, Cervical cancer, MAD2",
author = "Younghye Kim and Jung-Woo Choi and Ju-Han Lee and Kim, {Young Sik}",
year = "2014",
month = "1",
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doi = "10.1097/PGP.0000000000000082",
language = "English",
volume = "33",
pages = "517--523",
journal = "International Journal of Gynecological Pathology",
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TY - JOUR

T1 - MAD2 and CDC20 are upregulated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix

AU - Kim, Younghye

AU - Choi, Jung-Woo

AU - Lee, Ju-Han

AU - Kim, Young Sik

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Abnormal expression of the spindle assembly checkpoint proteins causes tumor cell aneuploidy, which has been reported in various malignancies. The expression of mitotic arrest deficient 2 (MAD2) and cell-division cycle 20 homolog (CDC20), the key spindle assembly checkpoint proteins, has not been studied in cervical carcinogenesis. In this study, we compared the expression of MAD2 and CDC20 in 332 cases, including normal cervical tissues, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and invasive squamous cell carcinomas (SCCs). Both MAD2 and CDC20 were overexpressed in the nuclei or cytoplasm of dysplastic and malignant tumor cells. The frequency of MAD2 overexpression was markedly increased from undetectable (0/100) in normal cervical tissues and 2% (1/50) in low-grade squamous intraepithelial lesions to 67.1% (53/79) in HSILs and 52.4% (54/103) in SCCs. Similarly, CDC20 was overexpressed in 49.4% (39/79) of HSILs and 22.3% (23/103) of SCCs, whereas CDC20 was not detectable (0/100) in normal cervical tissues and overexpressed only in 8.0% (4/50) of low-grade squamous intraepithelial lesions. In SCC cases, MAD2 overexpression correlated with a patient age of less than 60 yr (P=0.043), nonkeratinizing histologic type (P=0.018), and a lesser degree of stromal invasion (P=0.026). In conclusion, MAD2 and CDC20 overexpression was increased in HSILs and SCCs, suggesting their involvement in the initiation of cervical cancers. Controlling CDC20 and MAD2 expression may be a therapeutic strategy for cervical cancer.

AB - Abnormal expression of the spindle assembly checkpoint proteins causes tumor cell aneuploidy, which has been reported in various malignancies. The expression of mitotic arrest deficient 2 (MAD2) and cell-division cycle 20 homolog (CDC20), the key spindle assembly checkpoint proteins, has not been studied in cervical carcinogenesis. In this study, we compared the expression of MAD2 and CDC20 in 332 cases, including normal cervical tissues, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and invasive squamous cell carcinomas (SCCs). Both MAD2 and CDC20 were overexpressed in the nuclei or cytoplasm of dysplastic and malignant tumor cells. The frequency of MAD2 overexpression was markedly increased from undetectable (0/100) in normal cervical tissues and 2% (1/50) in low-grade squamous intraepithelial lesions to 67.1% (53/79) in HSILs and 52.4% (54/103) in SCCs. Similarly, CDC20 was overexpressed in 49.4% (39/79) of HSILs and 22.3% (23/103) of SCCs, whereas CDC20 was not detectable (0/100) in normal cervical tissues and overexpressed only in 8.0% (4/50) of low-grade squamous intraepithelial lesions. In SCC cases, MAD2 overexpression correlated with a patient age of less than 60 yr (P=0.043), nonkeratinizing histologic type (P=0.018), and a lesser degree of stromal invasion (P=0.026). In conclusion, MAD2 and CDC20 overexpression was increased in HSILs and SCCs, suggesting their involvement in the initiation of cervical cancers. Controlling CDC20 and MAD2 expression may be a therapeutic strategy for cervical cancer.

KW - CDC20

KW - Cervical cancer

KW - MAD2

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U2 - 10.1097/PGP.0000000000000082

DO - 10.1097/PGP.0000000000000082

M3 - Article

VL - 33

SP - 517

EP - 523

JO - International Journal of Gynecological Pathology

JF - International Journal of Gynecological Pathology

SN - 0277-1691

IS - 5

ER -