Periostin expression and its supposed roles in benign and malignant thyroid nodules: an immunohistochemical study of 105 cases

Abstract

Background: Thyroid tumors are often difficult to histopathologically diagnose, particularly follicular adenoma (FA) and follicular carcinoma (FC). Papillary carcinoma (PAC) has several histological subtypes. Periostin (PON), which is a non-collagenous extracellular matrix molecule, has been implicated in tumor invasiveness. We herein aimed to elucidate the expression status and localization of PON in thyroid tumors.

Method: We collected 105 cases of thyroid nodules, which included cases of adenomatous goiter, FA, microcarcinoma (MIC), PAC, FC, poorly differentiated carcinoma (PDCa), and undifferentiated carcinoma (UCa), and immunohistochemically examined the PON expression patterns of these lesions.

Results: Stromal PON deposition was detected in PAC and MIC, particularly in the solid/sclerosing subtype, whereas FA and FC showed weak deposition on the fibrous capsule. However, the invasive and/or extracapsular regions of microinvasive FC showed quite strong PON expression. Except for it, we could not find any significant histopathological differences between FA and FC. There were no other significant histopathological differences between FA and FC. Although PDCa showed a similar PON expression pattern to PAC, UCa exhibited stromal PON deposition in its invasive portions and cytoplasmic expression in its carcinoma cells. Although there was only one case of UCa, it showed strong PON immunopositivity. PAC and MIC showed similar patterns of stromal PON deposition, particularly at the invasive front.

Conclusions: PON may play a role in the invasion of thyroid carcinomas, particularly PAC and UCa, whereas it may act as a barrier to the growth of tumor cells in FA and minimally invasive FC.

Fig. 1

Histology of thyroid nodules. A Microcarcinoma (H&E). The nuclei of tumor cells showed a ground glass-like appearance, and tumor cells were surrounded by a sclerotic stroma. B Papillary carcinoma (H&E). Tumor cells, whose nuclei exhibited a ground glass-like appearance, formed irregular papillary structures. C Follicular adenoma (H&E). Follicles composed of tumor cells that exhibited mild nuclear atypia, but not capsular invasion, were observed (fc, fibrous capsule). D Minimally invasive follicular carcinoma (H&E). Tumor cells that exhibited mild atypia invaded the fibrous capsule (fc, fibrous capsule; arrows, capsular invasion). E Undifferentiated carcinoma (H&E). Polymorphous atypical short spindle-shaped cells that exhibited loose cell-cell adherence were arranged in fascicular structures or diffusely distributed. F Adenomatous goiter (H&E). Hyperplastic follicular cells without atypia were detected. Follicles contained colloid

Fig. 2

Results of immunohistochemical staining for periostin (PON) in each thyroid nodule. A Microcarcinoma. Immunopositivity for PON was observed in the sclerotic stroma. B Papillary carcinoma. Moderate to strong immunopositivity for PON was observed in the sclerotic stroma around the neoplastic follicles. C Follicular adenoma. Weak immunopositivity for PON was noted in the fibrous capsule (fc), together with some calcification (cal). D Widely invasive follicular carcinoma. Diffuse immunopositivity for PON was detected in the sclerotic stroma in the invasive regions. E Undifferentiated carcinoma. Strong immunopositivity for PON was diffusely observed in the stroma around cancer cells. (E, inset) PON immunoreactivity was also observed in the cytoplasm of cancer cells. F Adenomatous goiter. Very weak signals for PON were found in the pseudo-capsule (ps-fc) around the nodule in adenomatous goiter

Fig. 3

Immunohistochemical staining results for other thyroid tumor markers. In microcarcinoma, cancer cells exhibited strong positivity for galectin-3 (Gal-3) (A) and nuclear positivity for cyclin D1 (B). In papillary carcinoma, the cytoplasm of cancer cells was diffusely positive for Gal-3 (C). Undifferentiated carcinoma showed cytoplasmic immunopositivity for Gal-3 with a mosaic-like pattern (D). In papillary carcinoma, the luminal side of papillary structures was positive for Hector Battifora mesothelial 1 (HBME-1) (E), and tumor cells were diffusely positive for cytokeratin 19 (F). In undifferentiated carcinoma, cancer cells were diffusely positive for Ki-67 (G), whereas tumor cells in papillary carcinoma were sporadically positive for Ki-67 (H)