Expression of Matrix Metalloproteinases in Thyroid Follicular Neoplasm Fnab

Abstract

Fine-Needle Aspiration Biopsy (FNAB) thyroid nodules is difficult to distinguish betwen follicular malignancy and follicular benign lesion (1). The diagnosis of malignancy can only be made from histopathology examination by examing tumor invation to capsule and vascular (2,3). Matrix Metalloproteinase 9 (MMP-9) examination can be added to help making initial diagnosis. MMP-9 is a proteolytic enzyme that plays important role in cancer progressivity, especially in thyroid. High MMP-9 expression will lead to earlier degradation of thyroid and its will make the cell metastasist easier (4). This study aims to examine MMP-9 expression of thyroid follicular neoplasm FNAB.

We used 42 sample of follicular thyroid neoplasm FNAB obtained from the Pathology Anatomic laboratories in RSUP M Djamil Padang, West Sumatera. Immunohistochemical was staining with primary antibody MMP-9 then its expression were assessed in stroma and cytoplasmic tumour. In this study FNAB follicular thyroid nodules were found in the age group 21-45 years (57.1%), women (88.1%), and MMP-9 expression was found as much as 80.9%.

Introduction

Fine-Needle Aspiration Biopsy (FNAB) thyroid nodules is difficult to distinguish betwen follicular malignancy and follicular benign lesion (1). The diagnosis of malignancy can only be made from histopathology examination by examing tumor invation to capsule and vascular (2,3). Matrix Metalloproteinase 9 (MMP-9) examination can be added to help making initial diagnosis. MMP-9 is a proteolytic enzyme that plays important role in cancer progressivity, especially in thyroid. High MMP-9 expression will lead to earlier degradation of thyroid and its will make the cell metastasist easier (4). This study aims to examine MMP-9 expression of thyroid follicular neoplasm FNAB. We used 42 sample of follicular thyroid neoplasm FNAB obtained from the Pathology Anatomic laboratories in RSUP M Djamil Padang, West Sumatera. Immunohistochemical was staining with primary antibody MMP-9 then its expression were assessed in stroma and cytoplasmic tumour. In this study FNAB follicular thyroid nodules were found in the age group 21-45 years (57.1%), women (88.1%), and MMP-9 expression was found as much as 80.9%.

Procedures and Methods

This study was an observational study using a cross sectional study method consisting of 42 FNAB samples that were diagnosed with follicular neoplasms at M. Djamil Hospital Padang, West Sumatera in 2016-2017. The preparations are reviewed and representative preparations will be stained with MMP-9 antibodies. Immunocytochemical staining has been carried out in the Anatomy Pathology laboratories of Dr. RSUP. Cipto Mangunkusumo, Jakarta. We used primary antibody MMP-9 rabit monoclonal (Dual Endogenous Enzyme Block, Labelled Polymer-HRP, DAB + Substar buffer dan DAB + Chromogen, PB) then its expression is assessed in the stroma and cytoplasmic tumor. And preparations have been analyzed at the Baiturrahmah Faculty of Medicine.

Result

There were 53 cases of follicular neoplasm with 42 cases diagnosed based on Bethesda and used as research samples, consisting of 5 men (11.9 %) and 37 women (88,1%) (Diagram 1).

Diagram 1. Proportion of Patients by Sex

This study showed that the mean age of patients were 41 years old, with a minimum age was 17 years, and a maximum age was 63 years. The proportion of patients based on age, divided into 4 age groups, including <20 years old, 21-45 years old, 46-70 years old, and > 70 years old. The results of this study showed that there were 2 (4,8%) patients of <20 years old, 24 (57,1%) patients of 21-45 years old, 16 (38,1%) patients of 46-70 years old, and 0 patients of > 70 years old (Diagram 2).

Figure 1. Proportion of Patients by Age

In this study, 34 cases (80.9%) of the thyroid follicular neoplasm stained with MMP-9 were obtained (Diagram 3). The FNAB and imuocytology stain of thyroid follicular neoplasm FNAB can be seen in Figure 1 and 2.

Figure 2. Proportion of Patients by MMP-9 stain

Discussion

The study consisted of 42 cases diagnosed based on FNAB of thyroid follicular neoplasm including 88.1% women and 11.9% men. The same as a study Lim Hyeyeun ET all in the United States (1974-2013) there were 97% (77.276) cases of thyroid cancer diagnosed in women (5).

The higher thyroid nodule found in women than men is often associated with the role of female sex hormone factors, although until now through epidemiological studies this has not been proven. The role of female sex hormones that has been widely studied is the role of estrogen in the well-differentiated carcinogenesis of thyroid carcinoma. Estrogen has a proliferative effect on papillary thyroid carcinoma in vitro, but where there is cell proliferation that is mediated by the α (ERα) estrogen receptor, there will be an inhibitory effect by the β estrogen receptor (ERβ). These findings also prove that estrogen is involved in the differentiation process of thyroid carcinoma (6). The role of hormonal factors in thyroid carcinogenesis became clearer after it was discovered that pregnancy increases the risk of thyroid carcinoma due to increased thyroid hormones and serum estrogen levels (7).

Figure 3.

Figure 4. Microscopic of thyroid follicular neoplasm FNAB with H&E stain (100x and 200x)

This study showed that the mean age of patients were 41 years old, with a minimum age was 17 years, and a maximum age was 63 years. The results of this study showed that there were 2 (4,8%) patients of <20 years old, 24 (57,1%) patients of 21-45 years old, 16 (38,1%) patients of 46-70 years old, and no patients of > 70 years old. Savafi Ali, 2017 in Iran found that the highest rate of prevalence in thyroid cancer was observed at the age of 45 years at the time of diagnosis (8). Along with the aging process, cells will undergo DNA mutations including mitochondrial DNA which can increase the production of free radicals (ROS). The oxidative damage cycle that instructs ROS will play a direct role in the initiation of carcinogenesis and increase the potential for metastatic tumors (9).

Fine needle aspiration biopsy (FNAB) is important in evaluating thyroid nodule patients, reducing unnecessary surgery in patients with benign nodules, proper interpretation, and therapy for patients with malignant nodules. Agcaoglu et al reported that the factors that can determine the success of thyroid FNAB and reduce false-negative scores are the expertise of cytopathologists (10). Metalloproteinase matrix is ​​also used as a marker of the progression of malignancy. MMP can play an important role in the process of carcinogenesis, invasive cell tumors penetrate the basement membrane to the stroma and metastases (4,11). In this study, 34 cases (80.9%) of the thyroid follicular neoplasm stained with MMP-9 were obtained. The expression of MMP-9 stains positively on the cytoplasm and cell membrane with varying intensities. The authors hope this research can be continued by finding and assessing its histopathological tissue.

Figure 5. Microscopic of thyroid follicular neoplasm FNAB were positive with MMP-9 stain

Figure 6. Microscopic of thyroid follicular neoplasm FNAB were negative with MMP-9 stain

Conclution

Studi ini menemukan bahwa noda MMP 9 adalah 80,9% positif pada nodul folikel tiroid yang didiagnosis oleh FNAB.

Reference

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