Alteration of PTEN expression in endometrial carcinoma is associated with down-regulation of cyclin-dependent kinase inhibitor, p27

H. J. An, Y. H. Lee, N. H. Cho, J. Y. Shim, J. Y. Kim, C. Lee, S. J. Kim

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Aims: PTEN is a recently identified tumour suppressor inactivated in a wide variety of human cancers, including endometrial cancers. Mutation of the PTEN tumour suppressor gene has been reported in approximately 50-83% of endometrial adenocarcinoma. Despite this fact, study of the expression of PTEN protein in human tumours is limited. PTEN protein functions as a tumour suppressor by regulating the cell cycle and survival through signal transduction pathway. PTEN protein was considered to have a dual-specificity phosphatase activity, but it is now known that its principal physiological activity is mainly derived from its lipid phosphatase activity. The cyclin-dependent kinase inhibitor, p27, has been suggested as a downstream target of cell cycle arrest of PTEN in various in vitro studies. In this study, we evaluated the alteration of PTEN protein expression in endometrial carcinoma and assessed its relationship to the expression of p27, the presumed downstream target of PTEN. Methods and results: Immunohistochemical staining was performed on 66 cases of endometrial carcinoma including 61 endometrioid type and five serous type, using antibodies to PTEN and p27. Loss or decrease of PTEN expression was observed in 66% (40 / 61 cases) of uterine endometrioid carcinoma, whereas most uterine serous carcinoma (4 / 5 cases) showed intense PTEN expression. Four (30%) of 13 endometrial hyperplasia synchronous with endometrioid carcinoma demonstrated complete loss of PTEN expression. All endometrioid carcinoma synchronous with PTEN-negative endometrial hyperplasia showed loss of PTEN expression. Alteration of PTEN expression was not correlated with histological grade or stage. Decreased immunoreactivity of p27 was found in 48 cases (79%) of 61 endometrioid carcinoma, and 76% (36 cases) of them also showed loss or decrease of PTEN expression. Four of five uterine serous carcinoma revealed strong p27 immunoreactivity, all of which showed intense PTEN expression. A positive correlation between PTEN and p27 expression was statistically significant (Mantel-Haenszel χ2 test, P = 0.001). Immunoreactivity of p27 was not related to histological grade and clinical stage. Conclusion: These results show that PTEN and p27 are differentially expressed in endometrioid type carcinoma compared with those of the serous type, and suggest that the cyclin-dependent kinase inhibitor, p27, is a downstream target of PTEN-dependent cell cycle arrest in endometrial carcinoma.

Original languageEnglish
Pages (from-to)437-445
Number of pages9
JournalHistopathology
Volume41
Issue number5
DOIs
Publication statusPublished - 2002 Nov 26

Fingerprint

Cyclin-Dependent Kinase Inhibitor p27
Endometrioid Carcinoma
Endometrial Neoplasms
PTEN Phosphohydrolase
Down-Regulation
Endometrial Hyperplasia
Cell Cycle Checkpoints
Neoplasms
Dual-Specificity Phosphatases
Carcinoma
Tumor Suppressor Genes
Phosphoric Monoester Hydrolases
Signal Transduction
Cell Survival
Cell Cycle
Adenocarcinoma
Staining and Labeling
Lipids
Mutation
Antibodies

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology

Cite this

An, H. J. ; Lee, Y. H. ; Cho, N. H. ; Shim, J. Y. ; Kim, J. Y. ; Lee, C. ; Kim, S. J. / Alteration of PTEN expression in endometrial carcinoma is associated with down-regulation of cyclin-dependent kinase inhibitor, p27. In: Histopathology. 2002 ; Vol. 41, No. 5. pp. 437-445.
@article{9f8a96f81f7c424b92dac350ed31b549,
title = "Alteration of PTEN expression in endometrial carcinoma is associated with down-regulation of cyclin-dependent kinase inhibitor, p27",
abstract = "Aims: PTEN is a recently identified tumour suppressor inactivated in a wide variety of human cancers, including endometrial cancers. Mutation of the PTEN tumour suppressor gene has been reported in approximately 50-83{\%} of endometrial adenocarcinoma. Despite this fact, study of the expression of PTEN protein in human tumours is limited. PTEN protein functions as a tumour suppressor by regulating the cell cycle and survival through signal transduction pathway. PTEN protein was considered to have a dual-specificity phosphatase activity, but it is now known that its principal physiological activity is mainly derived from its lipid phosphatase activity. The cyclin-dependent kinase inhibitor, p27, has been suggested as a downstream target of cell cycle arrest of PTEN in various in vitro studies. In this study, we evaluated the alteration of PTEN protein expression in endometrial carcinoma and assessed its relationship to the expression of p27, the presumed downstream target of PTEN. Methods and results: Immunohistochemical staining was performed on 66 cases of endometrial carcinoma including 61 endometrioid type and five serous type, using antibodies to PTEN and p27. Loss or decrease of PTEN expression was observed in 66{\%} (40 / 61 cases) of uterine endometrioid carcinoma, whereas most uterine serous carcinoma (4 / 5 cases) showed intense PTEN expression. Four (30{\%}) of 13 endometrial hyperplasia synchronous with endometrioid carcinoma demonstrated complete loss of PTEN expression. All endometrioid carcinoma synchronous with PTEN-negative endometrial hyperplasia showed loss of PTEN expression. Alteration of PTEN expression was not correlated with histological grade or stage. Decreased immunoreactivity of p27 was found in 48 cases (79{\%}) of 61 endometrioid carcinoma, and 76{\%} (36 cases) of them also showed loss or decrease of PTEN expression. Four of five uterine serous carcinoma revealed strong p27 immunoreactivity, all of which showed intense PTEN expression. A positive correlation between PTEN and p27 expression was statistically significant (Mantel-Haenszel χ2 test, P = 0.001). Immunoreactivity of p27 was not related to histological grade and clinical stage. Conclusion: These results show that PTEN and p27 are differentially expressed in endometrioid type carcinoma compared with those of the serous type, and suggest that the cyclin-dependent kinase inhibitor, p27, is a downstream target of PTEN-dependent cell cycle arrest in endometrial carcinoma.",
author = "An, {H. J.} and Lee, {Y. H.} and Cho, {N. H.} and Shim, {J. Y.} and Kim, {J. Y.} and C. Lee and Kim, {S. J.}",
year = "2002",
month = "11",
day = "26",
doi = "10.1046/j.1365-2559.2002.01455.x",
language = "English",
volume = "41",
pages = "437--445",
journal = "Histopathology",
issn = "0309-0167",
publisher = "Wiley-Blackwell",
number = "5",

}

Alteration of PTEN expression in endometrial carcinoma is associated with down-regulation of cyclin-dependent kinase inhibitor, p27. / An, H. J.; Lee, Y. H.; Cho, N. H.; Shim, J. Y.; Kim, J. Y.; Lee, C.; Kim, S. J.

In: Histopathology, Vol. 41, No. 5, 26.11.2002, p. 437-445.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alteration of PTEN expression in endometrial carcinoma is associated with down-regulation of cyclin-dependent kinase inhibitor, p27

AU - An, H. J.

AU - Lee, Y. H.

AU - Cho, N. H.

AU - Shim, J. Y.

AU - Kim, J. Y.

AU - Lee, C.

AU - Kim, S. J.

PY - 2002/11/26

Y1 - 2002/11/26

N2 - Aims: PTEN is a recently identified tumour suppressor inactivated in a wide variety of human cancers, including endometrial cancers. Mutation of the PTEN tumour suppressor gene has been reported in approximately 50-83% of endometrial adenocarcinoma. Despite this fact, study of the expression of PTEN protein in human tumours is limited. PTEN protein functions as a tumour suppressor by regulating the cell cycle and survival through signal transduction pathway. PTEN protein was considered to have a dual-specificity phosphatase activity, but it is now known that its principal physiological activity is mainly derived from its lipid phosphatase activity. The cyclin-dependent kinase inhibitor, p27, has been suggested as a downstream target of cell cycle arrest of PTEN in various in vitro studies. In this study, we evaluated the alteration of PTEN protein expression in endometrial carcinoma and assessed its relationship to the expression of p27, the presumed downstream target of PTEN. Methods and results: Immunohistochemical staining was performed on 66 cases of endometrial carcinoma including 61 endometrioid type and five serous type, using antibodies to PTEN and p27. Loss or decrease of PTEN expression was observed in 66% (40 / 61 cases) of uterine endometrioid carcinoma, whereas most uterine serous carcinoma (4 / 5 cases) showed intense PTEN expression. Four (30%) of 13 endometrial hyperplasia synchronous with endometrioid carcinoma demonstrated complete loss of PTEN expression. All endometrioid carcinoma synchronous with PTEN-negative endometrial hyperplasia showed loss of PTEN expression. Alteration of PTEN expression was not correlated with histological grade or stage. Decreased immunoreactivity of p27 was found in 48 cases (79%) of 61 endometrioid carcinoma, and 76% (36 cases) of them also showed loss or decrease of PTEN expression. Four of five uterine serous carcinoma revealed strong p27 immunoreactivity, all of which showed intense PTEN expression. A positive correlation between PTEN and p27 expression was statistically significant (Mantel-Haenszel χ2 test, P = 0.001). Immunoreactivity of p27 was not related to histological grade and clinical stage. Conclusion: These results show that PTEN and p27 are differentially expressed in endometrioid type carcinoma compared with those of the serous type, and suggest that the cyclin-dependent kinase inhibitor, p27, is a downstream target of PTEN-dependent cell cycle arrest in endometrial carcinoma.

AB - Aims: PTEN is a recently identified tumour suppressor inactivated in a wide variety of human cancers, including endometrial cancers. Mutation of the PTEN tumour suppressor gene has been reported in approximately 50-83% of endometrial adenocarcinoma. Despite this fact, study of the expression of PTEN protein in human tumours is limited. PTEN protein functions as a tumour suppressor by regulating the cell cycle and survival through signal transduction pathway. PTEN protein was considered to have a dual-specificity phosphatase activity, but it is now known that its principal physiological activity is mainly derived from its lipid phosphatase activity. The cyclin-dependent kinase inhibitor, p27, has been suggested as a downstream target of cell cycle arrest of PTEN in various in vitro studies. In this study, we evaluated the alteration of PTEN protein expression in endometrial carcinoma and assessed its relationship to the expression of p27, the presumed downstream target of PTEN. Methods and results: Immunohistochemical staining was performed on 66 cases of endometrial carcinoma including 61 endometrioid type and five serous type, using antibodies to PTEN and p27. Loss or decrease of PTEN expression was observed in 66% (40 / 61 cases) of uterine endometrioid carcinoma, whereas most uterine serous carcinoma (4 / 5 cases) showed intense PTEN expression. Four (30%) of 13 endometrial hyperplasia synchronous with endometrioid carcinoma demonstrated complete loss of PTEN expression. All endometrioid carcinoma synchronous with PTEN-negative endometrial hyperplasia showed loss of PTEN expression. Alteration of PTEN expression was not correlated with histological grade or stage. Decreased immunoreactivity of p27 was found in 48 cases (79%) of 61 endometrioid carcinoma, and 76% (36 cases) of them also showed loss or decrease of PTEN expression. Four of five uterine serous carcinoma revealed strong p27 immunoreactivity, all of which showed intense PTEN expression. A positive correlation between PTEN and p27 expression was statistically significant (Mantel-Haenszel χ2 test, P = 0.001). Immunoreactivity of p27 was not related to histological grade and clinical stage. Conclusion: These results show that PTEN and p27 are differentially expressed in endometrioid type carcinoma compared with those of the serous type, and suggest that the cyclin-dependent kinase inhibitor, p27, is a downstream target of PTEN-dependent cell cycle arrest in endometrial carcinoma.

UR - http://www.scopus.com/inward/record.url?scp=0036428714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036428714&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2559.2002.01455.x

DO - 10.1046/j.1365-2559.2002.01455.x

M3 - Article

C2 - 12405911

AN - SCOPUS:0036428714

VL - 41

SP - 437

EP - 445

JO - Histopathology

JF - Histopathology

SN - 0309-0167

IS - 5

ER -