Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma

Glypican-3 is a membrane-bound proteoglycan whose expression has been linked to malignancies through the existence of both mutations and aberrant protein expression. Reports on glypican-3 expression in lung cancer were limited, with some evidence for loss of expression, which suggested a tumor-suppr...

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Published in:Modern pathology 2008-07, Vol.21 (7), p.817-825
Main Authors: Aviel-Ronen, Sarit, Lau, Suzanne K, Pintilie, Melania, Lau, Davina, Liu, Ni, Tsao, Ming Sound, Jothy, Serge
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Adult
Aged
Aged, 80 and over
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
DNA Mutational Analysis
Female
Gene Expression
glypican-3
Glypicans - genetics
Glypicans - metabolism
Humans
immunohistochemistry
Laboratory Medicine
Lung - anatomy & histology
Lung - metabolism
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Male
Medicine
Medicine & Public Health
Middle Aged
Mutation
Neuroblastoma
Oligonucleotide Array Sequence Analysis
original-article
Pathology
Patients
Proteins
quantitative PCR (qPCR)
RAS mutation
RNA, Messenger - metabolism
RNA, Neoplasm - analysis
Smoking
Tumors
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description Glypican-3 is a membrane-bound proteoglycan whose expression has been linked to malignancies through the existence of both mutations and aberrant protein expression. Reports on glypican-3 expression in lung cancer were limited, with some evidence for loss of expression, which suggested a tumor-suppressor role. We sought to evaluate glypican-3 expression in lung cancer at the protein and mRNA levels and correlate it with clinical, histological and genomic characteristics such as RAS mutation status. We used immunohistochemistry on tissue microarray to study glypican-3 expression in 97 patients, evaluated glypican-3 mRNA levels by quantitative polymerase chain reaction in 143 patients and identified RAS mutations by allele-specific oligonucleotide hybridization. We correlated the results with clinical and histological data. Glypican-3 immunostaining was negative in all normal lung tissues, but positive in 23% of lung carcinoma samples. High protein and mRNA expression was associated with squamous histology (positive stain in 55% of squamous cell carcinoma vs 8% of adenocarcinoma, P
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Reports on glypican-3 expression in lung cancer were limited, with some evidence for loss of expression, which suggested a tumor-suppressor role. We sought to evaluate glypican-3 expression in lung cancer at the protein and mRNA levels and correlate it with clinical, histological and genomic characteristics such as RAS mutation status. We used immunohistochemistry on tissue microarray to study glypican-3 expression in 97 patients, evaluated glypican-3 mRNA levels by quantitative polymerase chain reaction in 143 patients and identified RAS mutations by allele-specific oligonucleotide hybridization. We correlated the results with clinical and histological data. Glypican-3 immunostaining was negative in all normal lung tissues, but positive in 23% of lung carcinoma samples. High protein and mRNA expression was associated with squamous histology (positive stain in 55% of squamous cell carcinoma vs 8% of adenocarcinoma, P&lt;0.0001 for both immunostaining and mRNA). RAS mutations were highly associated with adenocarcinoma and low glypican-3 mRNA expression (P&lt;0.0001 for both). Among smokers, glypican-3 mRNA expression was reduced in adenocarcinoma patients (P=0.013), and was elevated in those with squamous cell carcinoma (P=0.03, interaction P=0.0009). These opposing associations also correlated with the smoking burden. Patients with tumors staining positively for glypican-3 smoked significantly more than patients with tumors staining negatively (P=0.013). No association was found between glypican-3 expression and patient outcome. In conclusion, glypican-3 was overexpressed in cancerous compared with normal lung tissue. Adenocarcinoma and squamous cell carcinoma had differential expression of glypican-3, with predilection to squamous cell carcinoma patients who smoked. Glypican-3 expression in squamous cell carcinoma as an oncofetal protein renders it a potential candidate marker for early detection of lung squamous cell carcinoma.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.2008.37</identifier><identifier>PMID: 18469798</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; DNA Mutational Analysis ; Female ; Gene Expression ; glypican-3 ; Glypicans - genetics ; Glypicans - metabolism ; Humans ; immunohistochemistry ; Laboratory Medicine ; Lung - anatomy &amp; histology ; Lung - metabolism ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Male ; Medicine ; Medicine &amp; Public Health ; Middle Aged ; Mutation ; Neuroblastoma ; Oligonucleotide Array Sequence Analysis ; original-article ; Pathology ; Patients ; Proteins ; quantitative PCR (qPCR) ; RAS mutation ; RNA, Messenger - metabolism ; RNA, Neoplasm - analysis ; Smoking ; Tumors</subject><ispartof>Modern pathology, 2008-07, Vol.21 (7), p.817-825</ispartof><rights>2008 United States &amp; Canadian Academy of Pathology</rights><rights>United States and Canadian Academy of Pathology, Inc. 2008</rights><rights>Copyright Nature Publishing Group Jul 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-93ca1aa5a92c081e86d329a41557f2c9845d766fdca3cb5d181207ddd5cb17fe3</citedby><cites>FETCH-LOGICAL-c494t-93ca1aa5a92c081e86d329a41557f2c9845d766fdca3cb5d181207ddd5cb17fe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18469798$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aviel-Ronen, Sarit</creatorcontrib><creatorcontrib>Lau, Suzanne K</creatorcontrib><creatorcontrib>Pintilie, Melania</creatorcontrib><creatorcontrib>Lau, Davina</creatorcontrib><creatorcontrib>Liu, Ni</creatorcontrib><creatorcontrib>Tsao, Ming Sound</creatorcontrib><creatorcontrib>Jothy, Serge</creatorcontrib><title>Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>Glypican-3 is a membrane-bound proteoglycan whose expression has been linked to malignancies through the existence of both mutations and aberrant protein expression. Reports on glypican-3 expression in lung cancer were limited, with some evidence for loss of expression, which suggested a tumor-suppressor role. We sought to evaluate glypican-3 expression in lung cancer at the protein and mRNA levels and correlate it with clinical, histological and genomic characteristics such as RAS mutation status. We used immunohistochemistry on tissue microarray to study glypican-3 expression in 97 patients, evaluated glypican-3 mRNA levels by quantitative polymerase chain reaction in 143 patients and identified RAS mutations by allele-specific oligonucleotide hybridization. We correlated the results with clinical and histological data. Glypican-3 immunostaining was negative in all normal lung tissues, but positive in 23% of lung carcinoma samples. High protein and mRNA expression was associated with squamous histology (positive stain in 55% of squamous cell carcinoma vs 8% of adenocarcinoma, P&lt;0.0001 for both immunostaining and mRNA). RAS mutations were highly associated with adenocarcinoma and low glypican-3 mRNA expression (P&lt;0.0001 for both). Among smokers, glypican-3 mRNA expression was reduced in adenocarcinoma patients (P=0.013), and was elevated in those with squamous cell carcinoma (P=0.03, interaction P=0.0009). These opposing associations also correlated with the smoking burden. Patients with tumors staining positively for glypican-3 smoked significantly more than patients with tumors staining negatively (P=0.013). No association was found between glypican-3 expression and patient outcome. In conclusion, glypican-3 was overexpressed in cancerous compared with normal lung tissue. Adenocarcinoma and squamous cell carcinoma had differential expression of glypican-3, with predilection to squamous cell carcinoma patients who smoked. Glypican-3 expression in squamous cell carcinoma as an oncofetal protein renders it a potential candidate marker for early detection of lung squamous cell carcinoma.</description><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>DNA Mutational Analysis</subject><subject>Female</subject><subject>Gene Expression</subject><subject>glypican-3</subject><subject>Glypicans - genetics</subject><subject>Glypicans - metabolism</subject><subject>Humans</subject><subject>immunohistochemistry</subject><subject>Laboratory Medicine</subject><subject>Lung - anatomy &amp; histology</subject><subject>Lung - metabolism</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine &amp; 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RAS mutations were highly associated with adenocarcinoma and low glypican-3 mRNA expression (P&lt;0.0001 for both). Among smokers, glypican-3 mRNA expression was reduced in adenocarcinoma patients (P=0.013), and was elevated in those with squamous cell carcinoma (P=0.03, interaction P=0.0009). These opposing associations also correlated with the smoking burden. Patients with tumors staining positively for glypican-3 smoked significantly more than patients with tumors staining negatively (P=0.013). No association was found between glypican-3 expression and patient outcome. In conclusion, glypican-3 was overexpressed in cancerous compared with normal lung tissue. Adenocarcinoma and squamous cell carcinoma had differential expression of glypican-3, with predilection to squamous cell carcinoma patients who smoked. 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subjects Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Adult
Aged
Aged, 80 and over
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
DNA Mutational Analysis
Female
Gene Expression
glypican-3
Glypicans - genetics
Glypicans - metabolism
Humans
immunohistochemistry
Laboratory Medicine
Lung - anatomy & histology
Lung - metabolism
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Male
Medicine
Medicine & Public Health
Middle Aged
Mutation
Neuroblastoma
Oligonucleotide Array Sequence Analysis
original-article
Pathology
Patients
Proteins
quantitative PCR (qPCR)
RAS mutation
RNA, Messenger - metabolism
RNA, Neoplasm - analysis
Smoking
Tumors
title Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma
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