Immunohistochemical demonstration of alteration of ß-catenin during tumor metastasis by different mechanisms according to histology in lung cancer

Xianhua Xu, Ji Eun Kim, Ping Li Sun, Seol Bong Yoo, Hyojin Kim, Yan Jin, Jin-Haeng Chung

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Abstract

The protein ß-catenin exhibits a dual function in cells, by acting as a major structural component of cell-cell adherens junctions and as a central signaling molecule in the Wnt signaling pathway. However, how the regulation of ß-catenin expression during tumor metastasis in non-small cell lung cancer (NSCLC) varies according to histological type remains unclear. To investigate the regulatory mechanism of ß-catenin on tumor metastasis, the present study compared the expression of Wnt1, ß-catenin and E-cadherin in 41 primary NSCLC tumors and their corresponding metastatic lesions by immunohistochemistry. Altered expression of ß-catenin was more frequent in the metastatic tumors (34/41, 82.9%) than in the corresponding primary tumors (24/41, 58.5%; P<0.05). There were 12 cases [nine of adenocarcinoma (ADC) and three of squamous cell carcinoma (SqCC)] that revealed discordant ß-catenin expression between the primary tumors and the corresponding metastatic lesions. Of these, 11 cases (11/12, 91.7%; nine ADCs and two SqCCs) demonstrated acquired ß-catenin alterations in the metastatic lesions. Subgroup analysis of these nine ADCs revealed that six cases (6/9, 66.7%) were accompanied by E-cadherin loss but no Wnt1 overexpression. Subgroup analysis of the three SqCCs revealed discordant ß-catenin expression. Two cases (2/3, 66.7%) demonstrated acquired ß-catenin expression during metastatic progression with Wnt1 overexpression but no change in E-cadherin expression. One case of SqCC revealed normal ß-catenin expression in the metastasis although the expression was aberrant in the primary tumor. The results of the present study revealed that the changes in ß-catenin expression occurred during tumor metastasis by different mechanisms, depending on histological type. The alterations in ß-catenin expression may be regulated by a cadherin-catenin system in ADCs with reduced membranous expression of E-cadherin, but mediated by Wnt1 overexpression in SqCCs with cytoplasmic or nuclear transition types.

Original languageEnglish
Pages (from-to)311-318
Number of pages8
JournalExperimental and Therapeutic Medicine
Volume9
Issue number2
DOIs
StatePublished - 1 Jan 2015

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Catenins
Lung Neoplasms
Histology
Neoplasm Metastasis
Neoplasms
Cadherins
Non-Small Cell Lung Carcinoma
Squamous Cell Carcinoma
Adherens Junctions
Wnt Signaling Pathway
Intercellular Junctions
Cellular Structures

Keywords

  • E-cadherin
  • Lung cancer
  • Wnt1
  • ß-catenin

Cite this

@article{eff9010161154a098422c1222ead36ae,
title = "Immunohistochemical demonstration of alteration of {\ss}-catenin during tumor metastasis by different mechanisms according to histology in lung cancer",
abstract = "The protein {\ss}-catenin exhibits a dual function in cells, by acting as a major structural component of cell-cell adherens junctions and as a central signaling molecule in the Wnt signaling pathway. However, how the regulation of {\ss}-catenin expression during tumor metastasis in non-small cell lung cancer (NSCLC) varies according to histological type remains unclear. To investigate the regulatory mechanism of {\ss}-catenin on tumor metastasis, the present study compared the expression of Wnt1, {\ss}-catenin and E-cadherin in 41 primary NSCLC tumors and their corresponding metastatic lesions by immunohistochemistry. Altered expression of {\ss}-catenin was more frequent in the metastatic tumors (34/41, 82.9{\%}) than in the corresponding primary tumors (24/41, 58.5{\%}; P<0.05). There were 12 cases [nine of adenocarcinoma (ADC) and three of squamous cell carcinoma (SqCC)] that revealed discordant {\ss}-catenin expression between the primary tumors and the corresponding metastatic lesions. Of these, 11 cases (11/12, 91.7{\%}; nine ADCs and two SqCCs) demonstrated acquired {\ss}-catenin alterations in the metastatic lesions. Subgroup analysis of these nine ADCs revealed that six cases (6/9, 66.7{\%}) were accompanied by E-cadherin loss but no Wnt1 overexpression. Subgroup analysis of the three SqCCs revealed discordant {\ss}-catenin expression. Two cases (2/3, 66.7{\%}) demonstrated acquired {\ss}-catenin expression during metastatic progression with Wnt1 overexpression but no change in E-cadherin expression. One case of SqCC revealed normal {\ss}-catenin expression in the metastasis although the expression was aberrant in the primary tumor. The results of the present study revealed that the changes in {\ss}-catenin expression occurred during tumor metastasis by different mechanisms, depending on histological type. The alterations in {\ss}-catenin expression may be regulated by a cadherin-catenin system in ADCs with reduced membranous expression of E-cadherin, but mediated by Wnt1 overexpression in SqCCs with cytoplasmic or nuclear transition types.",
keywords = "E-cadherin, Lung cancer, Wnt1, {\ss}-catenin",
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T1 - Immunohistochemical demonstration of alteration of ß-catenin during tumor metastasis by different mechanisms according to histology in lung cancer

AU - Xu, Xianhua

AU - Kim, Ji Eun

AU - Sun, Ping Li

AU - Yoo, Seol Bong

AU - Kim, Hyojin

AU - Jin, Yan

AU - Chung, Jin-Haeng

PY - 2015/1/1

Y1 - 2015/1/1

N2 - The protein ß-catenin exhibits a dual function in cells, by acting as a major structural component of cell-cell adherens junctions and as a central signaling molecule in the Wnt signaling pathway. However, how the regulation of ß-catenin expression during tumor metastasis in non-small cell lung cancer (NSCLC) varies according to histological type remains unclear. To investigate the regulatory mechanism of ß-catenin on tumor metastasis, the present study compared the expression of Wnt1, ß-catenin and E-cadherin in 41 primary NSCLC tumors and their corresponding metastatic lesions by immunohistochemistry. Altered expression of ß-catenin was more frequent in the metastatic tumors (34/41, 82.9%) than in the corresponding primary tumors (24/41, 58.5%; P<0.05). There were 12 cases [nine of adenocarcinoma (ADC) and three of squamous cell carcinoma (SqCC)] that revealed discordant ß-catenin expression between the primary tumors and the corresponding metastatic lesions. Of these, 11 cases (11/12, 91.7%; nine ADCs and two SqCCs) demonstrated acquired ß-catenin alterations in the metastatic lesions. Subgroup analysis of these nine ADCs revealed that six cases (6/9, 66.7%) were accompanied by E-cadherin loss but no Wnt1 overexpression. Subgroup analysis of the three SqCCs revealed discordant ß-catenin expression. Two cases (2/3, 66.7%) demonstrated acquired ß-catenin expression during metastatic progression with Wnt1 overexpression but no change in E-cadherin expression. One case of SqCC revealed normal ß-catenin expression in the metastasis although the expression was aberrant in the primary tumor. The results of the present study revealed that the changes in ß-catenin expression occurred during tumor metastasis by different mechanisms, depending on histological type. The alterations in ß-catenin expression may be regulated by a cadherin-catenin system in ADCs with reduced membranous expression of E-cadherin, but mediated by Wnt1 overexpression in SqCCs with cytoplasmic or nuclear transition types.

AB - The protein ß-catenin exhibits a dual function in cells, by acting as a major structural component of cell-cell adherens junctions and as a central signaling molecule in the Wnt signaling pathway. However, how the regulation of ß-catenin expression during tumor metastasis in non-small cell lung cancer (NSCLC) varies according to histological type remains unclear. To investigate the regulatory mechanism of ß-catenin on tumor metastasis, the present study compared the expression of Wnt1, ß-catenin and E-cadherin in 41 primary NSCLC tumors and their corresponding metastatic lesions by immunohistochemistry. Altered expression of ß-catenin was more frequent in the metastatic tumors (34/41, 82.9%) than in the corresponding primary tumors (24/41, 58.5%; P<0.05). There were 12 cases [nine of adenocarcinoma (ADC) and three of squamous cell carcinoma (SqCC)] that revealed discordant ß-catenin expression between the primary tumors and the corresponding metastatic lesions. Of these, 11 cases (11/12, 91.7%; nine ADCs and two SqCCs) demonstrated acquired ß-catenin alterations in the metastatic lesions. Subgroup analysis of these nine ADCs revealed that six cases (6/9, 66.7%) were accompanied by E-cadherin loss but no Wnt1 overexpression. Subgroup analysis of the three SqCCs revealed discordant ß-catenin expression. Two cases (2/3, 66.7%) demonstrated acquired ß-catenin expression during metastatic progression with Wnt1 overexpression but no change in E-cadherin expression. One case of SqCC revealed normal ß-catenin expression in the metastasis although the expression was aberrant in the primary tumor. The results of the present study revealed that the changes in ß-catenin expression occurred during tumor metastasis by different mechanisms, depending on histological type. The alterations in ß-catenin expression may be regulated by a cadherin-catenin system in ADCs with reduced membranous expression of E-cadherin, but mediated by Wnt1 overexpression in SqCCs with cytoplasmic or nuclear transition types.

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