Diagnostic role of galectin-3 immunohistochemistry in thyroid lesions

Karishma Sarin; Ranjeev Bhagat; RP S. Punia; Arjun Das; Uma Handa

doi:10.4103/jhnps.jhnps_37_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 10 | Issue : 2 | Page : 152-156

Diagnostic role of galectin-3 immunohistochemistry in thyroid lesions

Karishma Sarin¹, Ranjeev Bhagat¹, RP S. Punia¹, Arjun Das², Uma Handa¹
¹ Department of Pathology, Government Medical College and Hospital, Chandigarh, India
² Department of ENT, Government Medical College and Hospital, Chandigarh, India

Date of Submission	22-Jun-2022
Date of Decision	02-Aug-2022
Date of Acceptance	11-Aug-2022
Date of Web Publication	15-Dec-2022

Correspondence Address:
Ranjeev Bhagat
Department of Pathology, Government Medical College and Hospital Sec 32 Chandigarh
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jhnps.jhnps_37_22

Abstract

Background: Galectin-3 (Gal-3) is a good diagnostic marker for thyroid cancer. Evaluation of diagnostic accuracy of this marker complements the morphological assessment of a particular thyroid lesion. The aim of this study was to evaluate the immunohistochemical expression and diagnostic role of Gal-3 in various surgically resected thyroid lesions. Materials and Methods: Surgically resected thyroid specimens from 50 patients with hematoxylin and eosin (H and E)- and Gal-3-stained sections were studied. Results: The age of the patients ranged from 14 to 64 years. Of the 50 patients, 12 (24%) were male and 38 (76%) were females. Various histopathological diagnoses included were inflammatory lesions 8 (16%), hyperplastic lesions 15 (30%), and benign 2 (4%) and malignant 25 (50%) lesions. On quantitative analysis of Gal-3 immunostaining, 16/16 (100%) of the papillary thyroid carcinoma (PTC) cases showed a positive expression. In the rest of the malignant cases, 5 (20%) of follicular thyroid carcinoma, 3 (12%) of medullary thyroid carcinoma, and 1 (4%) of anaplastic thyroid carcinoma showed a negative expression. The PTC cases showed a statistically significant difference from the rest of the benign lesions (P = 0.000). In PTC cases, the sensitivity of Gal-3 came out to be 100%, specificity was 64%, positive predictive value was 75.3%, negative predictive value was 100%, and accuracy was 82%. Conclusion: The data thus obtained indicate that Gal-3 is a valuable marker for differentiating classical PTC and its common variants (follicular variant and microcarcinoma in our study) from the other benign and malignant lesions. Gal-3 as a diagnostic marker for thyroid cancer can lead to improved outcomes for individuals diagnosed with equivocal or suspicious lesions.

Keywords: Follicular adenoma, galectin-3, papillary carcinoma, thyroiditis

How to cite this article:
Sarin K, Bhagat R, S. Punia R P, Das A, Handa U. Diagnostic role of galectin-3 immunohistochemistry in thyroid lesions. J Head Neck Physicians Surg 2022;10:152-6

How to cite this URL:
Sarin K, Bhagat R, S. Punia R P, Das A, Handa U. Diagnostic role of galectin-3 immunohistochemistry in thyroid lesions. J Head Neck Physicians Surg [serial online] 2022 [cited 2023 Jun 4];10:152-6. Available from: https://www.jhnps.org/text.asp?2022/10/2/152/363923

Introduction

Thyroid cancers are one of the common tumors encountered in endocrine organs. They represent approximately 3.8% of all the new cancers diagnosed each year.^[1] Majority of them originate from the thyroid follicular cells and are frequently encountered in a younger population.^[2]

Galectins are carbohydrate-binding proteins belonging to β-galactosidase-binding lectins. Galectin-3 (Gal-3) is a chimera type of galectin. It is encoded by LGALS3 gene located on chromosome 14. Gal-3 plays an important role in mediating cell adhesion, activation of neutrophils and macrophages, inflammation, fibrogenesis, cell differentiation, and host defense.^[3],[4] Its expression is well known in papillary thyroid carcinoma (PTC) and can be expressed infrequently in benign lesions of thyroid. However, it never occurs in normal thyroid tissue.

Gal-3 is widely expressed by various tissues such as organs of digestive system, lungs, urogenital system, kidney, heart along with myeloid cells, fibroblasts, epithelial cells, and endothelial cells.^[4] It is located in cytoplasm, and it shuttles into nucleus and can also be released extracellularly.^[3],[5] This study was conducted to evaluate the expression of Gal-3 on various benign and malignant lesions of thyroid.

Aims and objectives

This study was conducted to evaluate the immunohistochemical expression of Gal-3 in different types of surgically resected thyroid lesions and to see if they can be useful for the diagnosis of challenging cases.

Materials and Methods

This was a prospective study where 50 cases of thyroidectomy were collected and purposive sampling was done for the study. The formalin-fixed paraffin-embedded tissues were stained with hematoxylin and eosin (H and E) and examined under light microscopy. The ideal sections were selected for each case, and immunohistochemistry (IHC) Gal-3 was applied in all the cases along with positive control (benign prostatic tissue). The H and E-stained slides were evaluated independently by two observers before giving the histopathological diagnosis.

Statistical analysis

Chi-square test and Fisher's exact test were applied for categorical variables. The results, obtained thereby, have been represented in terms of frequencies and percentages. Student's t-test was used for the measurable data. Parametric test (Student's t-test) was applied for the normally distributed data. Measurable data have been presented as mean/standard deviation and other descriptive statistics. P < 0.05 was considered to be statistically significant.

Results

Out of the 50 cases, there were 12 males (24%) and 38 (76%) females with a male: female ratio of 1:3.2 and an age range of 14–64 years (mean: 36.64 ± 11.13). Out of total, 25 (50%) cases were malignant lesions of thyroid while the other 25 (50%) were benign. The most common symptoms included weight loss, palpitations, change in voice, and difficulty in swallowing.

Based on the histopathological features of the thyroidectomy specimens, the lesions were characterized as inflammatory, hyperplastic, and neoplastic. The neoplastic lesions were further divided into benign and malignant. The number of cases in neoplastic category is mentioned in [Table 1].

Table 1: Distribution of various neoplastic lesions

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IHC for Gal-3 was applied on all the cases, and the grading of the staining was done based on intensity and distribution. Based on the intensity of staining, it was categorized as no staining (Grade 0), weak (Grade 1), moderate (Grade 2), and intense (Grade 3) expression. Based on the extent of staining, it was divided into focal and diffuse.

Distribution of benign lesions and galectin-3 expression

Goiter (nodular hyperplasia)

They comprised 10 cases of solitary colloid nodule, 3 cases of multinodular goiter (MNG), and 2 cases of adenomatoid goiter. On histopathological examination (HPE), they showed predominantly variably sized colloid filled follicles lined by benign follicular cells. Secondary changes were noted in a few cases. Among the 10 cases of solitary colloid nodule, 4 of them showed positivity for Gal-3. One showed focal Grade 1, one showed focal Grade 2, and two cases showed focal Grade 3 staining; the rest of the six cases were negative. Two cases of adenomatoid goiter were focally positive; one was Grade 1 and the other was Grade 2. Out of the three cases of MNG, one showed focal Grade 2 positive staining while the other two were negative.

Lymphocytic thyroiditis

There were total six cases. On HPE, there was presence of lymphocytic infiltrate with prominent germinal centers, which was destroying the thyroid follicles at places along with Hurthle cell change. Five out of six cases showed Gal-3 positivity. Two cases showed focal Grade 2 staining; three showed focal Grade 3 staining while one case was negative [Figure 1].

Figure 1: Histopathology and negative expression of Galectin 3 in colloid goiter (a,b) however endothelial cells are positive. Negative expression of Galectin 3 in lymphocytic thyroiditis however histiocytes shows focal positivity (c,d) and histopathology and negative expression of Galectin 3 in granulomatous thyroiditis (e,f) however inflammatory cells are positive

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Granulomatous thyroiditis

There were two cases. On HPE, noncaseating granulomas along with the lymphoid follicles and multinucleated giant cells were noted. Both were Gal-3 negative [Figure 1].

Follicular adenoma

There were two cases. On HPE, they showed complete encapsulation. The tumor cells were arranged in closely packed follicles, sheets and cords. There was no evidence of capsular or vascular invasion. Both were Gal-3 negative [Figure 1].

Distribution of malignant lesions and galectin-3 expression

Papillary thyroid carcinoma

Out of 25 malignant cases, 16 were PTC. Among them, there was one case each of follicular variant and micropapillary carcinoma types. In all these tumors, papillary architecture was noted except in follicular variant where the tumor was arranged as variably sized follicles separated by thin fibrous septae. However, the nuclear features in both were same. Psammoma bodies were noted in 8/16 (50%) cases. In 5/16 (31.3%) cases, the tumor was present in a background of lymphocytic thyroiditis. In papillary microcarcinoma, the thyroid parenchyma showed microscopic foci of tumor (size <0.5cm) arranged in follicular architecture. Few mitotic figures were also noted.

All cases of PTC showed Gal-3 positivity. Four out of 16 (25%) PTC cases showed Grade 3 staining [Figure 2], 11/16 (68.7%) cases showed Grade 2 positivity, and 1/16 (6.3%) showed Grade 1 staining. Gal-3 in the cases of PTC was significantly different from the others (P = 0.000) [Figure 3].

Figure 2: Histopathology and negative expression of Galectin 3 in Follicular Adenoma (2a,2b). Positive expression of Galectin 3 in Follicular variant of PTC (2c, 2d) and Classical PTC (2e, 2f)

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Figure 3: Based upon intensity and distribution of Gal-3, statistic difference of PTC cases from rest of the benign lesions

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Malignant lesions other than papillary thyroid carcinoma

There were 5/25 cases of follicular thyroid carcinoma (FTC). HPE showed a tumor with tumor cells arranged in the form of follicles, microfollicles, and small islands. Invasion of tumor through the capsule into the thyroid parenchyma was noted. There was no evidence of vascular invasion in any of them. There were 3/25 cases of medullary thyroid carcinoma (MTC). In MTC, the tumor was arranged in nested and organoid patterns. Stroma showed eosinophilic hyaline material deposition. Areas of calcification were also noted. There was a 1/25 case of anaplastic thyroid carcinoma (ATC). In ATC, the tumor was arranged in sheets, moderately pleomorphic cells with round-to-oval to spindle-shaped nuclei. Numerous atypical mitotic figures were noted. All the cases of FTC, MTC, and ATC were negative for Gal-3 [Figure 2].

For PTC, the sensitivity of Gal-3 was 100%, specificity was 64%, positive predictive value (PPV) was 75.3%, negative predictive value (NPV) was 100%, and accuracy was 82%.

Discussion

Gal-3 is a very important and well-known marker in thyroid malignancies. There are a few studies, which shed light on the role of Gal-3 in the benign lesions of thyroid. This study focuses on studying the expression of Gal-3 in benign as well as malignant lesions.

The most common malignant lesion of thyroid is PTC.^[6],[7],[8] This is replicated in our study with PTC forming 32% of all cases and 64% of malignant lesions (16 cases). For the confirmation of thyroid malignancies, particularly for identification of PTC and its variants, IHC is a very important auxiliary tool. Gal-3 is a very important and well-known marker for PTC.^{[7],[9],[10],[11]} Some authors suggest that alteration of Gal-3 expression is an early event in PTC progression and thus may be involved in tumorigenesis.^[12] We had seen that the expression of Gal-3 was diffuse and intense in all the cases of PTC [Figure 3].

Furthermore, earlier different studies had shown 45%–80% of cases of FTC being Gal-3 positive.^{[11],[13],[14]} One of the recent studies showed variable results in FTC.^[15] However, in our study, out of five cases of FTC, none showed Gal-3 expression. Furthermore, some authors mention that Gal-3 is negative in follicular adenomas.^[7],[16] Both our cases of follicular adenoma were negative for Gal-3. None of our cases of MTC and ATC showed Gal-3 positivity. This is concordant with the other studies.^[15]

Of the benign lesions, nodular hyperplasia is the most common.^[11] These formed 15 cases (30%) in our study in the form of solitary colloid nodule, MNG, and adenomatoid goiter. Benign goiters can show some focal Gal-3 positivity of variable intensity. In lymphocytic thyroiditis, the positivity was seen in the follicular cells localized around the lymphoid follicle. The follicular cells, which were entrapped in areas of chronic lymphocytic inflammation, were also positive. The most likely explanation for the Gal-3 expression of non-neoplastic follicular cells in an inflamed area are neo-synthesis affected by cytokines secreted by inflammatory cells or the simple permeation of Gal-3 abundantly shed by lymphocytes into the neighboring follicular cells.^{[17],[18],[19],[20]}

The present study found that to differentiate PTC including its variants cases from the other lesions, the sensitivity of Gal-3 was 100%, specificity was 64%, PPV was 75.3%, NPV was 100% and accuracy was 82%. This was comparable to many other studies. In fact, the sensitivity and NPV are 100% in our study which is much more important^{[7],[10],[11],[21]} [Table 2].

Table 2: Comparison of sensitivity, specificity, positive predictive value, negative predictive value, P value, and diagnostic accuracy of galectin-3 in diagnosing papillary thyroid carcinoma and its variants in various studies

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Limitations

In the present study, the sample size was small and there was an unequal distribution of cases of the various follicular patterned thyroid lesions. However, the role of Gal-3 in follicular patterned lesions still remains unclear and has to be further evaluated in future studies.

Conclusion

The data thus obtained indicate that Gal-3 is a valuable antibody for differentiating classical PTC and its common variants (follicular variant and microcarcinoma) from the other benign and malignant lesions. In cases of lymphocytic thyroiditis, the positive Gal-3 expression may indicate its origin due to immunoresponse to the transformed follicular cells. Positive expression of microcarcinomas, in a subset of lymphocytic thyroiditis, may indicate that the precursor lesions of thyroid cancer may be present in these thyroid lesions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical approval

The permission was taken from Institutional Ethics Committee prior to starting the project. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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