Correlation of G1 cyclins and cyclin-dependent kinase inhibitors relative to human papillomavirus infection in the uterine cervical lesions

Namhoon Cho, Hee Jeong Ahn, YoungTae Kim, Jae Wook Kim

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Abstract

We attempted to investigate the relationship between G1 cyclins and cyclin-dependent kinase inhibitors (CDKIs) while also taking into account earlier studies about the relationship between GI cyclins and human papillomavirus (HPV) status. Previously, we observed that cyclin D was downregulated in cases associated with HPV, while cyclin E played a leading role in neoplastic transformation. In this study, we analyzed the expression of CDKIs such as p21(WAF1/CIP1) p16(INK4A), and p27(KIP1) by means of immunohistochemistry in 22 cases of normal cervix, six cases of adenocarcinoma, 30 cases of cervical intraepithelial neoplasia (CIN), and 41 cases of squamous cell carcinoma (SCC). Stratum intermedium and parabasalis demonstrated strong intranuclear staining for all CDKIs. Reserve-cell hyperplasia and koilocytes revealed strong expression of CDKIs, whereas the neoplastic transformation in squamous lesions showed significantly decreased expression (ANOVA, p<.05). While normal endocervical cells revealed focal and weak expression to CDKIs, adenocarcinoma as well as glandular dysplasia revealed strong expression for all CDKIs but p16(INK4A). Both p16(INK4A) and cyclin D were negative in adenocarcinoma, and p16(INK4A) may be independent of cyclin D. There was strong correlation between cyclin E and p27(KIP1), and cyclin E and p21(WAF1)/CIP1 as well as among CDKIs. P16(INK4A) expression in case of SCC in cases associated with HPV type 16/18 was higher than in those lacking any type of HPV (t-test, p=.023). Downregulation of cyclin D in SCC associated with HPV seems to be inversely correlated with a relative overexpression of p16(INK4A). On the other hand, p21(WAF1/CIP1) and p27(KIP1) demonstrated lower expressions in HPV-positive cases than in cases devoid of HPV, but they were not statistically significant. In conclusion, all CDKIs were downregulated in neoplastic transformation, with p16(INK4A) being relatively increased in SCC cases associated with HPV where cyclin D was kept inert. In addition, cyclin E could be activated in neoplastic transformation by eluding p21(WAF1/CIP1) and p27(KIP1).

Original languageEnglish
Pages (from-to)61-71
Number of pages11
JournalInternational Journal of Surgical Pathology
Volume7
Issue number2
DOIs
Publication statusPublished - 1999 Jan 1

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Cyclin G1
Cyclin-Dependent Kinase Inhibitor p16
Papillomavirus Infections
Cyclin-Dependent Kinases
Cyclin D
Cyclin E
Squamous Cell Carcinoma
Adenocarcinoma
Down-Regulation
Human papillomavirus 18
Cervical Intraepithelial Neoplasia
Cyclins
Human papillomavirus 16
Cervix Uteri
Hyperplasia
Analysis of Variance
Immunohistochemistry
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

@article{5796044ec14542f68dd28414a676662a,
title = "Correlation of G1 cyclins and cyclin-dependent kinase inhibitors relative to human papillomavirus infection in the uterine cervical lesions",
abstract = "We attempted to investigate the relationship between G1 cyclins and cyclin-dependent kinase inhibitors (CDKIs) while also taking into account earlier studies about the relationship between GI cyclins and human papillomavirus (HPV) status. Previously, we observed that cyclin D was downregulated in cases associated with HPV, while cyclin E played a leading role in neoplastic transformation. In this study, we analyzed the expression of CDKIs such as p21(WAF1/CIP1) p16(INK4A), and p27(KIP1) by means of immunohistochemistry in 22 cases of normal cervix, six cases of adenocarcinoma, 30 cases of cervical intraepithelial neoplasia (CIN), and 41 cases of squamous cell carcinoma (SCC). Stratum intermedium and parabasalis demonstrated strong intranuclear staining for all CDKIs. Reserve-cell hyperplasia and koilocytes revealed strong expression of CDKIs, whereas the neoplastic transformation in squamous lesions showed significantly decreased expression (ANOVA, p<.05). While normal endocervical cells revealed focal and weak expression to CDKIs, adenocarcinoma as well as glandular dysplasia revealed strong expression for all CDKIs but p16(INK4A). Both p16(INK4A) and cyclin D were negative in adenocarcinoma, and p16(INK4A) may be independent of cyclin D. There was strong correlation between cyclin E and p27(KIP1), and cyclin E and p21(WAF1)/CIP1 as well as among CDKIs. P16(INK4A) expression in case of SCC in cases associated with HPV type 16/18 was higher than in those lacking any type of HPV (t-test, p=.023). Downregulation of cyclin D in SCC associated with HPV seems to be inversely correlated with a relative overexpression of p16(INK4A). On the other hand, p21(WAF1/CIP1) and p27(KIP1) demonstrated lower expressions in HPV-positive cases than in cases devoid of HPV, but they were not statistically significant. In conclusion, all CDKIs were downregulated in neoplastic transformation, with p16(INK4A) being relatively increased in SCC cases associated with HPV where cyclin D was kept inert. In addition, cyclin E could be activated in neoplastic transformation by eluding p21(WAF1/CIP1) and p27(KIP1).",
author = "Namhoon Cho and Ahn, {Hee Jeong} and YoungTae Kim and Kim, {Jae Wook}",
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T1 - Correlation of G1 cyclins and cyclin-dependent kinase inhibitors relative to human papillomavirus infection in the uterine cervical lesions

AU - Cho, Namhoon

AU - Ahn, Hee Jeong

AU - Kim, YoungTae

AU - Kim, Jae Wook

PY - 1999/1/1

Y1 - 1999/1/1

N2 - We attempted to investigate the relationship between G1 cyclins and cyclin-dependent kinase inhibitors (CDKIs) while also taking into account earlier studies about the relationship between GI cyclins and human papillomavirus (HPV) status. Previously, we observed that cyclin D was downregulated in cases associated with HPV, while cyclin E played a leading role in neoplastic transformation. In this study, we analyzed the expression of CDKIs such as p21(WAF1/CIP1) p16(INK4A), and p27(KIP1) by means of immunohistochemistry in 22 cases of normal cervix, six cases of adenocarcinoma, 30 cases of cervical intraepithelial neoplasia (CIN), and 41 cases of squamous cell carcinoma (SCC). Stratum intermedium and parabasalis demonstrated strong intranuclear staining for all CDKIs. Reserve-cell hyperplasia and koilocytes revealed strong expression of CDKIs, whereas the neoplastic transformation in squamous lesions showed significantly decreased expression (ANOVA, p<.05). While normal endocervical cells revealed focal and weak expression to CDKIs, adenocarcinoma as well as glandular dysplasia revealed strong expression for all CDKIs but p16(INK4A). Both p16(INK4A) and cyclin D were negative in adenocarcinoma, and p16(INK4A) may be independent of cyclin D. There was strong correlation between cyclin E and p27(KIP1), and cyclin E and p21(WAF1)/CIP1 as well as among CDKIs. P16(INK4A) expression in case of SCC in cases associated with HPV type 16/18 was higher than in those lacking any type of HPV (t-test, p=.023). Downregulation of cyclin D in SCC associated with HPV seems to be inversely correlated with a relative overexpression of p16(INK4A). On the other hand, p21(WAF1/CIP1) and p27(KIP1) demonstrated lower expressions in HPV-positive cases than in cases devoid of HPV, but they were not statistically significant. In conclusion, all CDKIs were downregulated in neoplastic transformation, with p16(INK4A) being relatively increased in SCC cases associated with HPV where cyclin D was kept inert. In addition, cyclin E could be activated in neoplastic transformation by eluding p21(WAF1/CIP1) and p27(KIP1).

AB - We attempted to investigate the relationship between G1 cyclins and cyclin-dependent kinase inhibitors (CDKIs) while also taking into account earlier studies about the relationship between GI cyclins and human papillomavirus (HPV) status. Previously, we observed that cyclin D was downregulated in cases associated with HPV, while cyclin E played a leading role in neoplastic transformation. In this study, we analyzed the expression of CDKIs such as p21(WAF1/CIP1) p16(INK4A), and p27(KIP1) by means of immunohistochemistry in 22 cases of normal cervix, six cases of adenocarcinoma, 30 cases of cervical intraepithelial neoplasia (CIN), and 41 cases of squamous cell carcinoma (SCC). Stratum intermedium and parabasalis demonstrated strong intranuclear staining for all CDKIs. Reserve-cell hyperplasia and koilocytes revealed strong expression of CDKIs, whereas the neoplastic transformation in squamous lesions showed significantly decreased expression (ANOVA, p<.05). While normal endocervical cells revealed focal and weak expression to CDKIs, adenocarcinoma as well as glandular dysplasia revealed strong expression for all CDKIs but p16(INK4A). Both p16(INK4A) and cyclin D were negative in adenocarcinoma, and p16(INK4A) may be independent of cyclin D. There was strong correlation between cyclin E and p27(KIP1), and cyclin E and p21(WAF1)/CIP1 as well as among CDKIs. P16(INK4A) expression in case of SCC in cases associated with HPV type 16/18 was higher than in those lacking any type of HPV (t-test, p=.023). Downregulation of cyclin D in SCC associated with HPV seems to be inversely correlated with a relative overexpression of p16(INK4A). On the other hand, p21(WAF1/CIP1) and p27(KIP1) demonstrated lower expressions in HPV-positive cases than in cases devoid of HPV, but they were not statistically significant. In conclusion, all CDKIs were downregulated in neoplastic transformation, with p16(INK4A) being relatively increased in SCC cases associated with HPV where cyclin D was kept inert. In addition, cyclin E could be activated in neoplastic transformation by eluding p21(WAF1/CIP1) and p27(KIP1).

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