Down-regulation of cytoplasmic PLZF correlates with high tumor grade and tumor aggression in non-small cell lung carcinoma

Guang Qian Xiao; Faqian Li; Jennifer Findeis-Hosey; Ollivier Hyrien; Pamela D. Unger; Lu Xiao; Richard Dunne; Eric S. Kim; Qi Yang; Loralee McMahon; David E. Burstein

doi:10.1016/j.humpath.2015.06.021

Down-regulation of cytoplasmic PLZF correlates with high tumor grade and tumor aggression in non-small cell lung carcinoma

Guang Qian Xiao, Faqian Li, Jennifer Findeis-Hosey, Ollivier Hyrien, Pamela D. Unger, Lu Xiao, Richard Dunne, Eric S. Kim, Qi Yang, Loralee McMahon, David E. Burstein

Laboratory Medicine and Pathology

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Abstract

There are currently no effective prognostic biomarkers for lung cancer. Promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor, has a role in cell cycle progression and tumorigenicity in various cancers. The expression and value of PLZF in lung carcinoma, particularly in the subclass of non-small cell lung carcinoma (NSCLC), has not been studied. Our aim was to study the immunohistochemical expression of PLZF in lung adenocarcinoma and squamous cell carcinoma and correlate the alteration of PLZF expression with tumor differentiation, lymph node metastasis, tumor stage, and overall survival. A total of 296 NSCLCs being mounted on tissue microarray (181 adenocarcinomas and 91 squamous cell carcinomas) were investigated. Moderate to strong expression of PLZF was found in the cytoplasm of all the nonneoplastic respiratory epithelium and most (89.9%) well-differentiated adenocarcinoma. The proportions of moderately differentiated, poorly differentiated adenocarcinoma, and paired lymph node adenocarcinoma metastases that demonstrated negative or only weak PLZF reactivity were 75.6%, 97.2%, and 89.9%, respectively. The expression of PLZF in squamous cell carcinoma was mostly weak or absent and significantly lower than that in adenocarcinoma of the same grade (P <.0005). The loss of cytoplasmic PLZF strongly correlated with high tumor grade and lymph node metastasis in both squamous carcinoma and adenocarcinoma (P <.0001). Down-regulation of PLZF also correlated with higher tumor stage and shorter overall survival (P <.05). These results support a prognostic value for loss of cytoplasmic PLZF expression in the stratification of NSCLC and a possible role of cytoplasmic shift and down-regulation of PLZF in the pathogenesis of NSCLC.

Original language	English (US)
Pages (from-to)	1607-1615
Number of pages	9
Journal	Human pathology
Volume	46
Issue number	11
DOIs	https://doi.org/10.1016/j.humpath.2015.06.021
State	Published - Nov 2015

Bibliographical note

Funding Information:
Funding/Support: The project described in this publication was partly supported by the University of Rochester Clinical and Translational Science Institute (Award No. UL1 TR000042 ) from the National Center for Advancing Translational Sciences of the National Institutes of Health . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

Aggression
Cytoplasmic
Differentiation
Non-small cell lung carcinoma
PLZF

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@article{df573c13485a494e997f7123c09a76dd,

title = "Down-regulation of cytoplasmic PLZF correlates with high tumor grade and tumor aggression in non-small cell lung carcinoma",

abstract = "There are currently no effective prognostic biomarkers for lung cancer. Promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor, has a role in cell cycle progression and tumorigenicity in various cancers. The expression and value of PLZF in lung carcinoma, particularly in the subclass of non-small cell lung carcinoma (NSCLC), has not been studied. Our aim was to study the immunohistochemical expression of PLZF in lung adenocarcinoma and squamous cell carcinoma and correlate the alteration of PLZF expression with tumor differentiation, lymph node metastasis, tumor stage, and overall survival. A total of 296 NSCLCs being mounted on tissue microarray (181 adenocarcinomas and 91 squamous cell carcinomas) were investigated. Moderate to strong expression of PLZF was found in the cytoplasm of all the nonneoplastic respiratory epithelium and most (89.9%) well-differentiated adenocarcinoma. The proportions of moderately differentiated, poorly differentiated adenocarcinoma, and paired lymph node adenocarcinoma metastases that demonstrated negative or only weak PLZF reactivity were 75.6%, 97.2%, and 89.9%, respectively. The expression of PLZF in squamous cell carcinoma was mostly weak or absent and significantly lower than that in adenocarcinoma of the same grade (P <.0005). The loss of cytoplasmic PLZF strongly correlated with high tumor grade and lymph node metastasis in both squamous carcinoma and adenocarcinoma (P <.0001). Down-regulation of PLZF also correlated with higher tumor stage and shorter overall survival (P <.05). These results support a prognostic value for loss of cytoplasmic PLZF expression in the stratification of NSCLC and a possible role of cytoplasmic shift and down-regulation of PLZF in the pathogenesis of NSCLC.",

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author = "Xiao, {Guang Qian} and Faqian Li and Jennifer Findeis-Hosey and Ollivier Hyrien and Unger, {Pamela D.} and Lu Xiao and Richard Dunne and Kim, {Eric S.} and Qi Yang and Loralee McMahon and Burstein, {David E.}",

note = "Funding Information: Funding/Support: The project described in this publication was partly supported by the University of Rochester Clinical and Translational Science Institute (Award No. UL1 TR000042 ) from the National Center for Advancing Translational Sciences of the National Institutes of Health . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

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AU - Xiao, Guang Qian

AU - Li, Faqian

AU - Findeis-Hosey, Jennifer

AU - Hyrien, Ollivier

AU - Unger, Pamela D.

AU - Xiao, Lu

AU - Dunne, Richard

AU - Kim, Eric S.

AU - Yang, Qi

AU - McMahon, Loralee

AU - Burstein, David E.

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PY - 2015/11

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N2 - There are currently no effective prognostic biomarkers for lung cancer. Promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor, has a role in cell cycle progression and tumorigenicity in various cancers. The expression and value of PLZF in lung carcinoma, particularly in the subclass of non-small cell lung carcinoma (NSCLC), has not been studied. Our aim was to study the immunohistochemical expression of PLZF in lung adenocarcinoma and squamous cell carcinoma and correlate the alteration of PLZF expression with tumor differentiation, lymph node metastasis, tumor stage, and overall survival. A total of 296 NSCLCs being mounted on tissue microarray (181 adenocarcinomas and 91 squamous cell carcinomas) were investigated. Moderate to strong expression of PLZF was found in the cytoplasm of all the nonneoplastic respiratory epithelium and most (89.9%) well-differentiated adenocarcinoma. The proportions of moderately differentiated, poorly differentiated adenocarcinoma, and paired lymph node adenocarcinoma metastases that demonstrated negative or only weak PLZF reactivity were 75.6%, 97.2%, and 89.9%, respectively. The expression of PLZF in squamous cell carcinoma was mostly weak or absent and significantly lower than that in adenocarcinoma of the same grade (P <.0005). The loss of cytoplasmic PLZF strongly correlated with high tumor grade and lymph node metastasis in both squamous carcinoma and adenocarcinoma (P <.0001). Down-regulation of PLZF also correlated with higher tumor stage and shorter overall survival (P <.05). These results support a prognostic value for loss of cytoplasmic PLZF expression in the stratification of NSCLC and a possible role of cytoplasmic shift and down-regulation of PLZF in the pathogenesis of NSCLC.

AB - There are currently no effective prognostic biomarkers for lung cancer. Promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor, has a role in cell cycle progression and tumorigenicity in various cancers. The expression and value of PLZF in lung carcinoma, particularly in the subclass of non-small cell lung carcinoma (NSCLC), has not been studied. Our aim was to study the immunohistochemical expression of PLZF in lung adenocarcinoma and squamous cell carcinoma and correlate the alteration of PLZF expression with tumor differentiation, lymph node metastasis, tumor stage, and overall survival. A total of 296 NSCLCs being mounted on tissue microarray (181 adenocarcinomas and 91 squamous cell carcinomas) were investigated. Moderate to strong expression of PLZF was found in the cytoplasm of all the nonneoplastic respiratory epithelium and most (89.9%) well-differentiated adenocarcinoma. The proportions of moderately differentiated, poorly differentiated adenocarcinoma, and paired lymph node adenocarcinoma metastases that demonstrated negative or only weak PLZF reactivity were 75.6%, 97.2%, and 89.9%, respectively. The expression of PLZF in squamous cell carcinoma was mostly weak or absent and significantly lower than that in adenocarcinoma of the same grade (P <.0005). The loss of cytoplasmic PLZF strongly correlated with high tumor grade and lymph node metastasis in both squamous carcinoma and adenocarcinoma (P <.0001). Down-regulation of PLZF also correlated with higher tumor stage and shorter overall survival (P <.05). These results support a prognostic value for loss of cytoplasmic PLZF expression in the stratification of NSCLC and a possible role of cytoplasmic shift and down-regulation of PLZF in the pathogenesis of NSCLC.

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Down-regulation of cytoplasmic PLZF correlates with high tumor grade and tumor aggression in non-small cell lung carcinoma

Abstract

Bibliographical note

Keywords

UN SDGs

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