Expression of Periostin in Patients with Non-Small Cell Lung Cancer: Correlation with Angiogenesis and Lymphangiogenesis

Abstract

The aim of this study was to evaluate periostin expression measured immunohistochemically in patients with non-small cell lung cancer (NSCLC) and to determine its association with clinical features, prognosis, angiogenesis, and lymphangiogenesis. We investigated periostin expression in a series of 88 patients with NSCLC. We also determined whether expression of periostin correlated with microvessel density and lymphatic microvessel density. Periostin was expressed in 42% of 88 patients. Its expression was significantly correlated with tumor size, lymph node metastasis, disease stage, and lymphatic invasion (p=0.0128, 0.0015, 0.0310 and 0.0273, respectively). There also was a significant relation between periostin expression and microvessel density and lymphatic microvessel density (all p<0.0001). Five-year survival rates were better in patients with negative periostin expression than in those with positive periostin expression (p=0.0044). Periostin expression was not significant in a multivariate additive model. Our findings show that periostin correlates with increased tumor progression and a worse prognosis in NSCLC, as well as with angiogenesis and lymphangiogenesis.

The multifaceted role of periostin in tumorigenesis

“…Its expression was significantly correlated with tumor size, disease stage, metastasis, and lymph node and lymphatic invasion [29]. Another report also demonstrated that high expression of periostin in either stroma or tumor epithelia, correlated with male gender, higher stage, higher pT category, and larger tumor size; similarly, periostin expression in stroma also correlated with tumor relapse [30].…”

“…There also was a significant relationship between periostin expression and density of both circulatory and lymphatic microvessels. NSCLC patients with periostin expression have significantly poorer survival rates than patients showing no periostin expression [3,29]. In addition, the serum periostin level may serve as a prognostic marker for NSCLC [31].…”

“…Thus, although periostin may confer a growth advantage to breast tumors in vivo by altering the microenvironment through promotion of angiogenesis, its overexpression may impose a growth disadvantage when the tumor cells are grown in culture [27]. In oral cancers and NSCLC, periostin is also frequently overexpressed and enhances angiogenesis and invasion [16,29]. Therefore, epithelial cell-derived tumors may gain the ability to generate more blood vessels, invade, and metastasize during late stages of tumorigenesis via the acquired expression of genes that normally are associated only with mesenchymal cells [27].…”

Interleukin-18 suppresses angiogenesis and lymphangiogenesis in implanted Lewis lung cancer

“…The occurrence, development and metastasis of solid tumors are often accompanied by the increase of new vessels and lymphatic vessels, while tumor metastasis is closely linked with the blood vessels and lymphatic vessels in tumor [13,14] . The metastasis of malignant tumors is mainly through blood and lymphatic channel, and vascular system and lymphatic system form a mutual transportation network structure.…”

Negative transcriptional regulation of the human periostin gene by YingYang-1 transcription factor

“…The role of POSTN in these contexts is supported by a growing number of evidence showing that POSTN is frequently over-expressed in cancer. POSTN is increased in breast cancer (Shao et al, 2004), as well as in cancer of the colon (Bao et al, 2004;Tai et al, 2005), prostate (Tischler et al, 2010), lung (Takanami et al, 2008), head and neck (Kudo et al, 2006;Siriwardena et al, 2006). Moreover, it has been postulated that POSTN is involved in tumor spread and metastatic growth by promoting cancer cell survival, invasion and angiogenesis (Bao et al, 2004;Kudo et al, 2006;Shao et al, 2004;Yan and Shao, 2006).…”