Cancer Letters

Cancer Letters

Volume 281, Issue 2, 28 August 2009, Pages 188-195
Cancer Letters

Loss of cellular polarity/cohesiveness in the invasive front of papillary thyroid carcinoma and periostin expression

https://doi.org/10.1016/j.canlet.2009.02.043Get rights and content

Abstract

Loss of cellular polarity/cohesiveness and periostin expression are involved in the epithelial–mesenchymal transition in the epithelial malignancies. Their roles in papillary thyroid carcinoma were studied. There was a significant correlation between the loss of cellular polarity/cohesiveness in the invasive front and the up-regulation of periostin in tumors. Both of them were significantly correlated with extrathyroid invasion, pT and lymph node metastasis. Our results suggest that the loss of cellular polarity/cohesiveness is a useful parameter for predicting prognosis of patients with papillary thyroid carcinoma, and periostin could be a candidate gene for therapeutic targeting for the blockage of tumor invasion.

Introduction

Papillary thyroid carcinoma (PTC) is the most common malignancy of the endocrine organs. It is well known that PTC has a good prognosis with a 10-year disease-free survival rate of more than 90%, but still about 10% of patients with PTC develop cancer recurrence or metastasis to the lymph nodes and/or distant organs after surgery and cancer death may occur. Previous studies have revealed that extrathyroid invasion at surgery is significantly correlated with PTC recurrence [1], [2], [3], [4]. Therefore identification of the molecular changes responsible for PTC development and invasiveness could be of great therapeutic significance for PTC treatment.

Recently, a novel gene periostin, also called osteoblast specific factor 2 (OSF-2) was shown by many authors to have a role in tumor growth, angiogenesis, invasiveness, and metastasis [4], [5], [6], [7], [8], [9], [10], [11], [12]. The up-regulation of periostin promoted tumor progression and angiogenesis through the up-regulation of vascular endothelial growth factor 2 expression in human breast cancers in a cultured cell experiment and tumor xenograft analysis in mice [5]. Non-small cell lung carcinoma patients with high serum periostin levels had significantly poorer survival than the patients with low serum levels [6]. Periostin creates a tumor-supportive microenvironment in the pancreas by sustaining fibrogenic stellate cell activity, therefore increased periostin expression is often accompanied by a more aggressive tumor phenotype [7]. Periostin is also frequently overexpressed and is believed to promote invasion and angiogenesis in oral squamous cell carcinoma, and so is believed to be a strong marker for metastasis in oral cancer patients [8]. Puppin et al. recently show that high expression of periostin is correlated with extrathyroid invasion, lymph node metastasis and higher grade staging in papillary thyroid carcinomas [12]. Most importantly, transduction of the periostin gene into 293T cells induced cell invasive activity through epithelial–mesenchymal transition (EMT) [13]. The expression of periostin is strikingly up-regulated in the EMT phenotype than in the epithelial phenotype of the squamous carcinoma cells lines [14]. EMT is a common event in PTC invasion, which features by a loss of epithelial properties and the acquisition of mesenchymal properties, including the loss of apical–basal polarity, loss of cell–cell adhesion, loss of E-cadherin expression, and overexpression of vimentin, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9, TGF-β, NFkβ, and integrin pathway members in the invasive front [13], [15], [16], [17], [18]. Taken together with our previous finding that loss of cellular polarity/cohesiveness was associated with a poor disease-free survival rate [1], [19], it raises the question what is the relationship between the loss of cellular polarity/cohesiveness and the clinical parameters in PTC such as the status of extrathyroid invasion and lymph node metastasis, and whether periostin expression plays a role in the development of PTC.

Our purpose is to solve the following questions: (1) What is the clinical significance of the loss of cellular polarity/cohesiveness in the invasive front of PTC? (2) What is the clinicopathological significance of differences in periostin expression in tumor and adjacent non-neoplastic tissue? (3) Is there any correlation between periostin expression and the loss of cellular polarity/cohesiveness in PTC?

Section snippets

Patients and specimens

Thyroid carcinoma tissues and matched non-neoplastic tissues were obtained from 68 patients with primary papillary thyroid carcinoma who were operated on at the Kuma Hospital, Kobe, Japan. Eight (11.8%) men and 60 (88.2%) women were enrolled in the study, and their mean age at surgery was 53.4 ± 15.8 years (mean ± SD, median = 57.5). Mean tumor size was 2.8 ± 1.5 cm (mean ± SD, median = 2.2). Extrathyroid invasion was present in 49 (72.1%) cases. Metastasis to the lymph node was histologically identified

Histological examination and classification

All HE sections were reviewed by two pathologists (Y.B and K.K). Of the 68 cases of PTC, 59 cases were diagnosed as PTC common type, three as PTC tall cell variant, three as PTC follicular variant, one as PTC diffuse scleorosing variant, and two as poorly differentiated PTC (Table 1). The matched non-neoplastic tissues showed histological features of normal thyroid, adenomatous goiter or Hashimoto’s disease.

The status of loss of cellular polarity/cohesiveness in the invasive front of PTC is

Discussion

In this study, we correlated the histological change of loss of cellular polarity/cohesiveness in the invasive front of PTC, which are the main morphological features of EMT, with the clinical parameters of PTC and found that loss of cellular polarity/cohesiveness in the invasive front was significantly associated with extrathyroid invasion and lymph node metastasis. We examined the expression of periostin, a gene involved in EMT, and detected its relationship with the clinicopathological

Conflict of interest statement

The authors declared no conflict of interest.

Acknowledgements

We send our sincere appreciation to Ms. Maekawa, at the Department of Pathology, Kuma hospital, Kobe, Japan for preparing fresh and frozen samples for us. Part of the research fund was covered by a scholarship to Yanhua Bai from Rotary Yoneyama Memorial Foundation, Japan.

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