Association between lymphangiogenesis-/micrometastasis- and adhesion-related molecules in resected stage I NSCLC.

Abstract

BACKGROUND:

The purpose of this study was to clarify the role and clinical significance of lymphangiogenesis/micrometastases and adhesion molecules in resected stage I non-small cell lung cancer (NSCLC).

METHODS:

Immunohistochemical (IHC) staining was used to analyze the protein expression of vascular endothelial growth factor-C (VEGF-C), VEGF, E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin in paraffin-embedded tumor samples from 117 well-characterized stage I NSCLC patients and to compare the protein expression, clinical variables and survival outcome. As a micrometastatic parameter in lymph nodes (LNs), cytokeratin (CK) staining was performed.

RESULTS:

The positive expression of VEGF-C and VEGF were detected in 54 (48.7%) and 86 (73.5%), respectively. We identified micrometastatic tumor cells in pathological N0 LNs in 34 (29.1%) of 117 patients. E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin were identified in 70 (59.8%), 41 (35.0%), 83 (70.9%), and 61 (52.1%) specimens, respectively. The VEGF-C expression was found more frequently in squamous cell carcinoma (SQ) and in the tumors with negative expression of beta-catenin than counter features. The VEGF expression was found more frequently in the tumors with a negative expression of E-cadherin. Micrometastasis was found more frequently in a pathological T2 status and in the tumors with a negative expression of alpha-catenin. Beta-catenin and gamma-catenin expressions were found less and more frequently in SQ, respectively. A univariate and multivariate survival analysis demonstrated that old age, pathological T2 status, and micrometastasis were independently associated with an increased risk of poor survival in the patients who underwent a surgical resection of stage I NSCLC.

CONCLUSIONS:

Complicated relationships exist between lymphangiogenesis/micrometastases and adhesion molecules with a specific histology. The detection of lymph nodal micrometastasis by CK may therefore be a useful marker for predicting a poor prognosis in patients who undergo a complete resection of stage I NSCLC.

• Authors: Toshihiro Yamashita, Hidetaka Uramoto, Takamitsu Onitsuka, Kenji Ono, Tetsuro Baba, Tetsuya So, Tomoko So, Mitsuhiro Takenoyama, Takeshi Hanagiri, Tsunehiro Oyama, Kosei Yasumoto
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 70 Issue 3 Pg. 320-8 (Dec 2010) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 20363046 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Cadherins
• Catenins
• Vascular Endothelial Growth Factors
• Keratins

Topics

• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Cadherins (genetics, metabolism)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology, physiopathology, surgery)
• Catenins (genetics, metabolism)
• Cell Adhesion
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Keratins (genetics, metabolism)
• Lung Neoplasms (genetics, metabolism, pathology, physiopathology, surgery)
• Lymph Nodes (metabolism, pathology)
• Lymphangiogenesis
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Staging
• Vascular Endothelial Growth Factors (genetics, metabolism)