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Estrogen Receptor-Beta Genotype, Seven Immunohistochemical Markers, and Human Lung Cancer

Song, Ji Young (2010) Estrogen Receptor-Beta Genotype, Seven Immunohistochemical Markers, and Human Lung Cancer. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Lung cancer is the leading cause of cancer death in the United States. However, few new and effective treatments are available for lung cancer. A comprehensive understanding of the multiple signaling pathways that lead to tumor growth is a prerequisite for more effective and targeted cancer treatments. The purpose of this research was to investigate the relationship between proteins [hepatocypte growth factor (HGF), c-Met, and estrogen receptor-beta (ER-beta)] and gene expression of ER-beta (ESR2) and lung cancer survival along with identifying meaningful expression patterns of seven biomarkers [HGF, c-Met, ER-alpha, ER-beta, progesterone receptor (PR), aromatase, and epidermal growth factor receptor (EGFR)]. We used immunohistochemistry to quantify the expression of seven proteins in primary lung tumor tissues from the Lung Cancer Specialized Program of Research Excellence substudy (N=204). The generalized linear mixed model approach, which controlled for sample type (tissue microarray vs. whole-section), showed high HGF expression associated negatively with advanced cancer stage (Pglobal=0.05) and positively with smoking (Pglobal=0.14). After accounting for stage and other factors, neither HGF nor c-Met expression predicted survival. Using a cluster algorithm, two groups were identified: (Cluster 1: high expression of ER-alpha ER-beta, cytoplasmic PR, EGFR, and aromatase; Cluster 2: high expression of HGF, c-Met, and nuclear PR). Two lung cancer subgroups exhibiting dissimilar 7-protein IHC expression patterns were similar in terms of host and tumor characteristics and in terms of overall survival (log rank test: p=0.69).Among 22 htSNPs of ESR2 gene, we have identified that rare allele of rs1256061 is associated with the maximum ER-beta expression among patients with adenocarcinoma, but not with squamous cell carcinoma.The results of this research enhanced the knowledge of the role of HGF and c-Met on lung cancer survival and also suggested that the relationship between genetic variation of ESR2 gene and protein expression may differ by lung cancer histology. Understanding the roles, the expression patterns, and the genetic of steroid hormones, growth factors and their receptors in lung cancer is of great public health significance because it may enable biologically directed and individually tailored treatment and their possible use as biomarkers for early detection and prevention.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Song, Ji
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWeissfeld, Joel
Committee MemberDiergaarde, Brenda B.diergaardeb@upmc.eduBBD3
Committee MemberSiegfried, Jill
Committee MemberBowser, Robert
Committee MemberLand, Stephanie
Date: 29 September 2010
Date Type: Completion
Defense Date: 1 July 2010
Approval Date: 29 September 2010
Submission Date: 27 June 2010
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: aromatase; biomarker; c-Met; ER-alpha; ESR2 gene; estrogen receptor beta; Hepatocyte growth factor; immunohistochemistry; lung cancer; polymorphisms; PR; single nucleotide polymorphisms; survival; ERGR; tissue microarray
Other ID:, etd-06272010-005007
Date Deposited: 10 Nov 2011 19:48
Last Modified: 19 Dec 2016 14:36


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