Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 8/2015

01-08-2015 | Original Article – Cancer Research

Comparison of the expression levels of molecular markers among the peripheral area and central area of primary tumor and metastatic lymph node tumor in patients with squamous cell carcinoma of the lung

Authors: Hibiki Udagawa, Genichiro Ishii, Masahiro Morise, Shigeki Umemura, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Hironobu Ohmatsu, Masahiro Tsuboi, Koichi Goto, Atsushi Ochiai, Yuichiro Ohe

Published in: Journal of Cancer Research and Clinical Oncology | Issue 8/2015

Login to get access

Abstract

Purpose

Immunohistochemical analysis for the identification of clinically relevant biomarkers is important. However, there have been no detailed reports about the heterogeneous expressions of the various markers in squamous cell carcinoma of the lung.

Methods

A total of 113 patients with squamous cell carcinoma of the lung with lymph node metastasis were included. The expression levels of 9 molecules (E-cadherin, S100A4, CD44, ALDH1, SOX2, EGFR, HER2, FGFR1 and VEGFR2) in the peripheral area and central area of primary tumor and metastatic lymph nodes were evaluated by immunohistochemistry. The differences in the staining scores of these molecules among the three areas were assessed. We also analyzed the relationships between the expression levels of these molecules and the recurrence-free survival.

Results

The E-cadherin expression was higher in the central area than in the peripheral area and metastatic lymph nodes (median staining score: 60 vs. 50, 30); the CD44 expression was higher in the central area than in the metastatic lymph nodes (117 vs. 90); and the EGFR expression was higher in the central area than in the peripheral area and metastatic lymph nodes (163 vs. 130, 110). Low CD44 expression in the central area, low EGFR expression in the peripheral area and high SOX2 expression in the metastatic lymph nodes were associated with a shorter recurrence-free survival (p < 0.01, p = 0.02, p = 0.03, respectively).

Conclusions

Our findings confirmed that some molecular markers exhibited different expression levels in anatomically different areas and suggested that area-by-area immunohistochemical analysis for biomarkers may provide useful information for more precise prediction of the recurrence.
Appendix
Available only for authorised users
Literature
go back to reference Andersson J, Linderholm B, Bergh J, Elmberger G (2004) HER-2/neu (c-erbB-2) evaluation in primary breast carcinoma by fluorescent in situ hybridization and immunohistochemistry with special focus on intratumor heterogeneity and comparison of invasive and in situ components. Appl Immunohistochem Mol Morphol 12:14–20PubMedCrossRef Andersson J, Linderholm B, Bergh J, Elmberger G (2004) HER-2/neu (c-erbB-2) evaluation in primary breast carcinoma by fluorescent in situ hybridization and immunohistochemistry with special focus on intratumor heterogeneity and comparison of invasive and in situ components. Appl Immunohistochem Mol Morphol 12:14–20PubMedCrossRef
go back to reference De Marzo AM, Bradshaw C, Sauvageot J, Epstein JI, Miller GJ (1998) CD44 and CD44v6 downregulation in clinical prostatic carcinoma: relation to Gleason grade and cytoarchitecture. Prostate 34:162–168PubMedCrossRef De Marzo AM, Bradshaw C, Sauvageot J, Epstein JI, Miller GJ (1998) CD44 and CD44v6 downregulation in clinical prostatic carcinoma: relation to Gleason grade and cytoarchitecture. Prostate 34:162–168PubMedCrossRef
go back to reference Deeb G, Wang J, Ramnath N, Slocum HK, Wiseman S, Beck A, Tan D (2004) Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry. Mod Pathol 17:430–439. doi:10.1038/modpathol.3800041 PubMedCrossRef Deeb G, Wang J, Ramnath N, Slocum HK, Wiseman S, Beck A, Tan D (2004) Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry. Mod Pathol 17:430–439. doi:10.​1038/​modpathol.​3800041 PubMedCrossRef
go back to reference Elzagheid A et al (2006) E-cadherin expression pattern in primary colorectal carcinomas and their metastases reflects disease outcome. World J Gastroenterol 12:4304–4309PubMedPubMedCentral Elzagheid A et al (2006) E-cadherin expression pattern in primary colorectal carcinomas and their metastases reflects disease outcome. World J Gastroenterol 12:4304–4309PubMedPubMedCentral
go back to reference Friedrichs K et al (1995) CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer. Cancer Res 55:5424–5433PubMed Friedrichs K et al (1995) CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer. Cancer Res 55:5424–5433PubMed
go back to reference Funai K et al (2003) Clinicopathologic characteristics of peripheral squamous cell carcinoma of the lung. Am J Surg Pathol 27:978–984PubMedCrossRef Funai K et al (2003) Clinicopathologic characteristics of peripheral squamous cell carcinoma of the lung. Am J Surg Pathol 27:978–984PubMedCrossRef
go back to reference Italiano A et al (2006) Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors. Ann Oncol 17:981–985. doi:10.1093/annonc/mdl038 PubMedCrossRef Italiano A et al (2006) Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors. Ann Oncol 17:981–985. doi:10.​1093/​annonc/​mdl038 PubMedCrossRef
go back to reference Nagatsuma AK, Aizawa M, Kuwata T, Doi T, Ohtsu A, Fujii H, Ochiai A (2014) Expression profiles of HER2, EGFR, MET and FGFR2 in a large cohort of patients with gastric adenocarcinoma. Gastric Cancer. doi:10.1007/s10120-014-0360-4 Nagatsuma AK, Aizawa M, Kuwata T, Doi T, Ohtsu A, Fujii H, Ochiai A (2014) Expression profiles of HER2, EGFR, MET and FGFR2 in a large cohort of patients with gastric adenocarcinoma. Gastric Cancer. doi:10.​1007/​s10120-014-0360-4
go back to reference Neri S et al (2012) Recruitment of podoplanin positive cancer-associated fibroblasts in metastatic lymph nodes predicts poor prognosis in pathological N2 stage III lung adenocarcinoma. Ann Surg Oncol 19:3953–3962. doi:10.1245/s10434-012-2421-4 PubMedCrossRef Neri S et al (2012) Recruitment of podoplanin positive cancer-associated fibroblasts in metastatic lymph nodes predicts poor prognosis in pathological N2 stage III lung adenocarcinoma. Ann Surg Oncol 19:3953–3962. doi:10.​1245/​s10434-012-2421-4 PubMedCrossRef
go back to reference Pirker R et al (2012) EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol 13:33–42. doi:10.1016/s1470-2045(11)70318-7 PubMedCrossRef Pirker R et al (2012) EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol 13:33–42. doi:10.​1016/​s1470-2045(11)70318-7 PubMedCrossRef
go back to reference Scartozzi M, Bearzi I, Berardi R, Mandolesi A, Fabris G, Cascinu S (2004) Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies. J Clin Oncol 22:4772–4778. doi:10.1200/JCO.2004.00.117 PubMedCrossRef Scartozzi M, Bearzi I, Berardi R, Mandolesi A, Fabris G, Cascinu S (2004) Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies. J Clin Oncol 22:4772–4778. doi:10.​1200/​JCO.​2004.​00.​117 PubMedCrossRef
go back to reference Scartozzi M, Bearzi I, Berardi R, Mandolesi A, Pierantoni C, Cascinu S (2007) Epidermal growth factor receptor (EGFR) downstream signalling pathway in primary colorectal tumours and related metastatic sites: optimising EGFR-targeted treatment options. Br J Cancer 97:92–97. doi:10.1038/sj.bjc.6603847 PubMedPubMedCentralCrossRef Scartozzi M, Bearzi I, Berardi R, Mandolesi A, Pierantoni C, Cascinu S (2007) Epidermal growth factor receptor (EGFR) downstream signalling pathway in primary colorectal tumours and related metastatic sites: optimising EGFR-targeted treatment options. Br J Cancer 97:92–97. doi:10.​1038/​sj.​bjc.​6603847 PubMedPubMedCentralCrossRef
go back to reference Schneider J et al (1999) Histologic grade and CD44 are independent predictors of axillary lymph node invasion in early (T1) breast cancer. Tumour Biol 20:319–330PubMedCrossRef Schneider J et al (1999) Histologic grade and CD44 are independent predictors of axillary lymph node invasion in early (T1) breast cancer. Tumour Biol 20:319–330PubMedCrossRef
go back to reference Wang X, Zhang J, Fan M, Zhou Q, Deng H, Aisharif MJ, Chen X (2009) The expression of E-cadherin at the invasive tumor front of oral squamous cell carcinoma: immunohistochemical and RT-PCR analysis with clinicopathological correlation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107:547–554. doi:10.1016/j.tripleo.2008.11.021 PubMedCrossRef Wang X, Zhang J, Fan M, Zhou Q, Deng H, Aisharif MJ, Chen X (2009) The expression of E-cadherin at the invasive tumor front of oral squamous cell carcinoma: immunohistochemical and RT-PCR analysis with clinicopathological correlation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107:547–554. doi:10.​1016/​j.​tripleo.​2008.​11.​021 PubMedCrossRef
Metadata
Title
Comparison of the expression levels of molecular markers among the peripheral area and central area of primary tumor and metastatic lymph node tumor in patients with squamous cell carcinoma of the lung
Authors
Hibiki Udagawa
Genichiro Ishii
Masahiro Morise
Shigeki Umemura
Shingo Matsumoto
Kiyotaka Yoh
Seiji Niho
Hironobu Ohmatsu
Masahiro Tsuboi
Koichi Goto
Atsushi Ochiai
Yuichiro Ohe
Publication date
01-08-2015
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 8/2015
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-015-1912-7

Other articles of this Issue 8/2015

Journal of Cancer Research and Clinical Oncology 8/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.