Multiplexed analysis of angiogenesis and lymphangiogenesis factors predicts outcome for non-small cell lung cancer patients

Valsamo Anagnostou, Dina G. Tiniakos, Marianthi Fotinou, Apostolos Achimastos, Konstantinos N. Syrigos

Research output: Contribution to journalArticle

Abstract

Angiogenesis and lymphangiogenesis are key components of non-small cell lung cancer (NSCLC) tumor growth and metastatic spread; however, the prognostic and predictive role of angiogenic and lymphangiogenic biomarkers remains controversial for NSCLC patients. We assessed VEGF, VEGFC, VEGFD, VEGFR3 protein expression, tumor microvessel, and lymphatic vessel (LmVD) density by immunohistochemistry in 103 NSCLC; biomarkers were analyzed individually as well as multi-plexed with each other. No correlations were identified between VEGF, VEGFC, VEGFD, or LmVD and clinical characteristics. VEGFR3 was correlated with VEGFC (p= 0.03), VEGFD (p<0.0001), and intratumor LmVD (p= 0.03). Tumors that did not express VEGFR3 had a worse prognosis (log rank p=0.03). VEGF was significantly correlated with survival in adenocarcinomas (log rank p= 0.014) but not in squamous cell carcinomas (log rank p= 0.5). Multivariate Cox regression analysis confirmed the independent prognostic potential of VEGFR3 (hazard ratio (HR)=0.05; 95% confidence intervals (CI)=0.008-0.32, p=0.002) for all patients and VEGF (HR=8.69, 95% CI=1.4-53.69, p=0.02) for adenocarcinomas. When bio-markers were multiplexed, only stage and VEGFC expression were independent predictors of survival for all patients. Weighted expression of VEGFC, VEGFR3, and stage was used to build a prognostic classifier for stage I-IIIA patients; patients in the low risk group had prolonged survival compared with high risk patients (log rank p= 0.02). There was no association between biomarkers and early recurrence or response to treatment. Angiogenic and lymphangiogenic biomarkers studied define subgroups of patients at high risk and may be useful for prognostic stratification of NSCLC patients especially those with early stage disease.

Original languageEnglish (US)
Pages (from-to)331-340
Number of pages10
JournalVirchows Archiv
Volume458
Issue number3
DOIs
StatePublished - Mar 2011
Externally publishedYes

Fingerprint

Lymphangiogenesis
Angiogenesis Inducing Agents
Non-Small Cell Lung Carcinoma
Vascular Endothelial Growth Factor A
Biomarkers
Survival
Lymphatic Vessel Tumors
Adenocarcinoma
Confidence Intervals
Tumor Biomarkers
Microvessels
Squamous Cell Carcinoma
Neoplasms
Immunohistochemistry
Regression Analysis
Recurrence

Keywords

  • Early stage
  • Lung cancer
  • Prognosis
  • VEGFC
  • VEGFR3

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Multiplexed analysis of angiogenesis and lymphangiogenesis factors predicts outcome for non-small cell lung cancer patients. / Anagnostou, Valsamo; Tiniakos, Dina G.; Fotinou, Marianthi; Achimastos, Apostolos; Syrigos, Konstantinos N.

In: Virchows Archiv, Vol. 458, No. 3, 03.2011, p. 331-340.

Research output: Contribution to journalArticle

Anagnostou, Valsamo ; Tiniakos, Dina G. ; Fotinou, Marianthi ; Achimastos, Apostolos ; Syrigos, Konstantinos N. / Multiplexed analysis of angiogenesis and lymphangiogenesis factors predicts outcome for non-small cell lung cancer patients. In: Virchows Archiv. 2011 ; Vol. 458, No. 3. pp. 331-340.
@article{5ada7d76c1444fdcb4f4a918d4233225,
title = "Multiplexed analysis of angiogenesis and lymphangiogenesis factors predicts outcome for non-small cell lung cancer patients",
abstract = "Angiogenesis and lymphangiogenesis are key components of non-small cell lung cancer (NSCLC) tumor growth and metastatic spread; however, the prognostic and predictive role of angiogenic and lymphangiogenic biomarkers remains controversial for NSCLC patients. We assessed VEGF, VEGFC, VEGFD, VEGFR3 protein expression, tumor microvessel, and lymphatic vessel (LmVD) density by immunohistochemistry in 103 NSCLC; biomarkers were analyzed individually as well as multi-plexed with each other. No correlations were identified between VEGF, VEGFC, VEGFD, or LmVD and clinical characteristics. VEGFR3 was correlated with VEGFC (p= 0.03), VEGFD (p<0.0001), and intratumor LmVD (p= 0.03). Tumors that did not express VEGFR3 had a worse prognosis (log rank p=0.03). VEGF was significantly correlated with survival in adenocarcinomas (log rank p= 0.014) but not in squamous cell carcinomas (log rank p= 0.5). Multivariate Cox regression analysis confirmed the independent prognostic potential of VEGFR3 (hazard ratio (HR)=0.05; 95{\%} confidence intervals (CI)=0.008-0.32, p=0.002) for all patients and VEGF (HR=8.69, 95{\%} CI=1.4-53.69, p=0.02) for adenocarcinomas. When bio-markers were multiplexed, only stage and VEGFC expression were independent predictors of survival for all patients. Weighted expression of VEGFC, VEGFR3, and stage was used to build a prognostic classifier for stage I-IIIA patients; patients in the low risk group had prolonged survival compared with high risk patients (log rank p= 0.02). There was no association between biomarkers and early recurrence or response to treatment. Angiogenic and lymphangiogenic biomarkers studied define subgroups of patients at high risk and may be useful for prognostic stratification of NSCLC patients especially those with early stage disease.",
keywords = "Early stage, Lung cancer, Prognosis, VEGFC, VEGFR3",
author = "Valsamo Anagnostou and Tiniakos, {Dina G.} and Marianthi Fotinou and Apostolos Achimastos and Syrigos, {Konstantinos N.}",
year = "2011",
month = "3",
doi = "10.1007/s00428-010-1015-4",
language = "English (US)",
volume = "458",
pages = "331--340",
journal = "Virchows Archiv",
issn = "0945-6317",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Multiplexed analysis of angiogenesis and lymphangiogenesis factors predicts outcome for non-small cell lung cancer patients

AU - Anagnostou, Valsamo

AU - Tiniakos, Dina G.

AU - Fotinou, Marianthi

AU - Achimastos, Apostolos

AU - Syrigos, Konstantinos N.

PY - 2011/3

Y1 - 2011/3

N2 - Angiogenesis and lymphangiogenesis are key components of non-small cell lung cancer (NSCLC) tumor growth and metastatic spread; however, the prognostic and predictive role of angiogenic and lymphangiogenic biomarkers remains controversial for NSCLC patients. We assessed VEGF, VEGFC, VEGFD, VEGFR3 protein expression, tumor microvessel, and lymphatic vessel (LmVD) density by immunohistochemistry in 103 NSCLC; biomarkers were analyzed individually as well as multi-plexed with each other. No correlations were identified between VEGF, VEGFC, VEGFD, or LmVD and clinical characteristics. VEGFR3 was correlated with VEGFC (p= 0.03), VEGFD (p<0.0001), and intratumor LmVD (p= 0.03). Tumors that did not express VEGFR3 had a worse prognosis (log rank p=0.03). VEGF was significantly correlated with survival in adenocarcinomas (log rank p= 0.014) but not in squamous cell carcinomas (log rank p= 0.5). Multivariate Cox regression analysis confirmed the independent prognostic potential of VEGFR3 (hazard ratio (HR)=0.05; 95% confidence intervals (CI)=0.008-0.32, p=0.002) for all patients and VEGF (HR=8.69, 95% CI=1.4-53.69, p=0.02) for adenocarcinomas. When bio-markers were multiplexed, only stage and VEGFC expression were independent predictors of survival for all patients. Weighted expression of VEGFC, VEGFR3, and stage was used to build a prognostic classifier for stage I-IIIA patients; patients in the low risk group had prolonged survival compared with high risk patients (log rank p= 0.02). There was no association between biomarkers and early recurrence or response to treatment. Angiogenic and lymphangiogenic biomarkers studied define subgroups of patients at high risk and may be useful for prognostic stratification of NSCLC patients especially those with early stage disease.

AB - Angiogenesis and lymphangiogenesis are key components of non-small cell lung cancer (NSCLC) tumor growth and metastatic spread; however, the prognostic and predictive role of angiogenic and lymphangiogenic biomarkers remains controversial for NSCLC patients. We assessed VEGF, VEGFC, VEGFD, VEGFR3 protein expression, tumor microvessel, and lymphatic vessel (LmVD) density by immunohistochemistry in 103 NSCLC; biomarkers were analyzed individually as well as multi-plexed with each other. No correlations were identified between VEGF, VEGFC, VEGFD, or LmVD and clinical characteristics. VEGFR3 was correlated with VEGFC (p= 0.03), VEGFD (p<0.0001), and intratumor LmVD (p= 0.03). Tumors that did not express VEGFR3 had a worse prognosis (log rank p=0.03). VEGF was significantly correlated with survival in adenocarcinomas (log rank p= 0.014) but not in squamous cell carcinomas (log rank p= 0.5). Multivariate Cox regression analysis confirmed the independent prognostic potential of VEGFR3 (hazard ratio (HR)=0.05; 95% confidence intervals (CI)=0.008-0.32, p=0.002) for all patients and VEGF (HR=8.69, 95% CI=1.4-53.69, p=0.02) for adenocarcinomas. When bio-markers were multiplexed, only stage and VEGFC expression were independent predictors of survival for all patients. Weighted expression of VEGFC, VEGFR3, and stage was used to build a prognostic classifier for stage I-IIIA patients; patients in the low risk group had prolonged survival compared with high risk patients (log rank p= 0.02). There was no association between biomarkers and early recurrence or response to treatment. Angiogenic and lymphangiogenic biomarkers studied define subgroups of patients at high risk and may be useful for prognostic stratification of NSCLC patients especially those with early stage disease.

KW - Early stage

KW - Lung cancer

KW - Prognosis

KW - VEGFC

KW - VEGFR3

UR - http://www.scopus.com/inward/record.url?scp=79954500386&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79954500386&partnerID=8YFLogxK

U2 - 10.1007/s00428-010-1015-4

DO - 10.1007/s00428-010-1015-4

M3 - Article

VL - 458

SP - 331

EP - 340

JO - Virchows Archiv

JF - Virchows Archiv

SN - 0945-6317

IS - 3

ER -