Cargando…

Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer

BACKGROUND: Human sodium iodide symporter (hNIS) gene over-expression is under active consideration worldwide as an alternative target molecule for breast cancer (BC) diagnosis and targeted radio-iodine treatment. However, the field demands better stratified analysis of endogenous hNIS expression ac...

Descripción completa

Detalles Bibliográficos
Autores principales: Chatterjee, Sushmita, Malhotra, Renu, Varghese, Frency, Bukhari, Amirali B., Patil, Asawari, Budrukkar, Ashwini, Parmar, Vani, Gupta, Sudeep, De, Abhijit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544659/
https://www.ncbi.nlm.nih.gov/pubmed/23342072
http://dx.doi.org/10.1371/journal.pone.0054055
_version_ 1782255820634849280
author Chatterjee, Sushmita
Malhotra, Renu
Varghese, Frency
Bukhari, Amirali B.
Patil, Asawari
Budrukkar, Ashwini
Parmar, Vani
Gupta, Sudeep
De, Abhijit
author_facet Chatterjee, Sushmita
Malhotra, Renu
Varghese, Frency
Bukhari, Amirali B.
Patil, Asawari
Budrukkar, Ashwini
Parmar, Vani
Gupta, Sudeep
De, Abhijit
author_sort Chatterjee, Sushmita
collection PubMed
description BACKGROUND: Human sodium iodide symporter (hNIS) gene over-expression is under active consideration worldwide as an alternative target molecule for breast cancer (BC) diagnosis and targeted radio-iodine treatment. However, the field demands better stratified analysis of endogenous hNIS expression across major BC subtypes. Therefore, we have analyzed subtype-specific variation of hNIS overexpression in breast tumor tissue samples by immunohistochemistry (IHC) and also report the development of a homogeneous, quantitative analysis method of digital IHC images. METHODS: hNIS expression was analyzed from 108 BC tissue samples by IHC. Sub-cellular localization of hNIS protein was analyzed by dual immunofluorescence (IF) staining method using hNIS and HER2 antibodies. An ImageJ based two-step digital analysis method was developed and applied for the bias-free analysis of the images. RESULTS: Staining of the tumor samples show 70% cases are hNIS positive indicating high incidence of hNIS positive cases in BC. More importantly, a subtype specific analysis done for the first time shows that hNIS expression is overly dominated in estrogen receptor (ER) positive cases than the receptor negative cases. Further, 56% of the ER+ve, PgR+ve, HER2-ve and 36% of ER+ve, PgR+ve, HER2+ve cases show highest intensity staining equivalent to the thyroid tissue. A significant positive correlation is also observed between hNIS and estrogen receptor expression (p = 0.0033, CI = 95%) suggesting hNIS mediated targeted radio-iodine therapy procedures may benefit both ER+ve, PgR+ve, HER2–ve as well as HER2+ve cases. Further, in a few cases, hNIS and HER2 protein localization is demonstrated by overlapping membrane co-expression. ImageJ based image analysis method shows over 70% match with manual pathological scoring method. CONCLUSION: The study indicates a positive link between hNIS and ER expression in BC. The quantitative IHC image analysis method reported here will further help in patient stratification and potentially benefit global clinical assessment where hNIS mediated targeted (131)I radio-ablative therapy is aimed.
format Online
Article
Text
id pubmed-3544659
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-35446592013-01-22 Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer Chatterjee, Sushmita Malhotra, Renu Varghese, Frency Bukhari, Amirali B. Patil, Asawari Budrukkar, Ashwini Parmar, Vani Gupta, Sudeep De, Abhijit PLoS One Research Article BACKGROUND: Human sodium iodide symporter (hNIS) gene over-expression is under active consideration worldwide as an alternative target molecule for breast cancer (BC) diagnosis and targeted radio-iodine treatment. However, the field demands better stratified analysis of endogenous hNIS expression across major BC subtypes. Therefore, we have analyzed subtype-specific variation of hNIS overexpression in breast tumor tissue samples by immunohistochemistry (IHC) and also report the development of a homogeneous, quantitative analysis method of digital IHC images. METHODS: hNIS expression was analyzed from 108 BC tissue samples by IHC. Sub-cellular localization of hNIS protein was analyzed by dual immunofluorescence (IF) staining method using hNIS and HER2 antibodies. An ImageJ based two-step digital analysis method was developed and applied for the bias-free analysis of the images. RESULTS: Staining of the tumor samples show 70% cases are hNIS positive indicating high incidence of hNIS positive cases in BC. More importantly, a subtype specific analysis done for the first time shows that hNIS expression is overly dominated in estrogen receptor (ER) positive cases than the receptor negative cases. Further, 56% of the ER+ve, PgR+ve, HER2-ve and 36% of ER+ve, PgR+ve, HER2+ve cases show highest intensity staining equivalent to the thyroid tissue. A significant positive correlation is also observed between hNIS and estrogen receptor expression (p = 0.0033, CI = 95%) suggesting hNIS mediated targeted radio-iodine therapy procedures may benefit both ER+ve, PgR+ve, HER2–ve as well as HER2+ve cases. Further, in a few cases, hNIS and HER2 protein localization is demonstrated by overlapping membrane co-expression. ImageJ based image analysis method shows over 70% match with manual pathological scoring method. CONCLUSION: The study indicates a positive link between hNIS and ER expression in BC. The quantitative IHC image analysis method reported here will further help in patient stratification and potentially benefit global clinical assessment where hNIS mediated targeted (131)I radio-ablative therapy is aimed. Public Library of Science 2013-01-14 /pmc/articles/PMC3544659/ /pubmed/23342072 http://dx.doi.org/10.1371/journal.pone.0054055 Text en © 2013 Chatterjee et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chatterjee, Sushmita
Malhotra, Renu
Varghese, Frency
Bukhari, Amirali B.
Patil, Asawari
Budrukkar, Ashwini
Parmar, Vani
Gupta, Sudeep
De, Abhijit
Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer
title Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer
title_full Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer
title_fullStr Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer
title_full_unstemmed Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer
title_short Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer
title_sort quantitative immunohistochemical analysis reveals association between sodium iodide symporter and estrogen receptor expression in breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544659/
https://www.ncbi.nlm.nih.gov/pubmed/23342072
http://dx.doi.org/10.1371/journal.pone.0054055
work_keys_str_mv AT chatterjeesushmita quantitativeimmunohistochemicalanalysisrevealsassociationbetweensodiumiodidesymporterandestrogenreceptorexpressioninbreastcancer
AT malhotrarenu quantitativeimmunohistochemicalanalysisrevealsassociationbetweensodiumiodidesymporterandestrogenreceptorexpressioninbreastcancer
AT varghesefrency quantitativeimmunohistochemicalanalysisrevealsassociationbetweensodiumiodidesymporterandestrogenreceptorexpressioninbreastcancer
AT bukhariamiralib quantitativeimmunohistochemicalanalysisrevealsassociationbetweensodiumiodidesymporterandestrogenreceptorexpressioninbreastcancer
AT patilasawari quantitativeimmunohistochemicalanalysisrevealsassociationbetweensodiumiodidesymporterandestrogenreceptorexpressioninbreastcancer
AT budrukkarashwini quantitativeimmunohistochemicalanalysisrevealsassociationbetweensodiumiodidesymporterandestrogenreceptorexpressioninbreastcancer
AT parmarvani quantitativeimmunohistochemicalanalysisrevealsassociationbetweensodiumiodidesymporterandestrogenreceptorexpressioninbreastcancer
AT guptasudeep quantitativeimmunohistochemicalanalysisrevealsassociationbetweensodiumiodidesymporterandestrogenreceptorexpressioninbreastcancer
AT deabhijit quantitativeimmunohistochemicalanalysisrevealsassociationbetweensodiumiodidesymporterandestrogenreceptorexpressioninbreastcancer