The Correlation between Proliferative Immunohistochemical Markers and Papillary Thyroid Carcinoma Aggressiveness

Abstract

Background and Objectives: Papillary thyroid carcinoma (PTC) is one of the most common malignancies of the endocrine system. In order to improve the ability to predict tumor behavior, several studies have been conducted to search for surrogate prognostic immunohistochemical tumor markers. Objective: To evaluate the correlation between the intensity of different immunohistochemical marker staining in PTC and the risk for extrathyroidal extension and metastases. Materials and Methods: The study comprised patients who underwent hemi- or total thyroidectomy. Thyroid tissues were immunohistochemically stained for different tumor proliferative markers: Minichromosome maintenance proteins 2 (MCM2), Ki-67 labeling index, E-Cadherin, Neuropilin-1 and Metallothionein. The correlation between the intensity of each marker staining and the final diagnosis (benign neoplasm and PTC) and the correlation between the intensity of each staining and tumor extrathyroidal extension and metastases were evaluated. Results: The study included 66 patients. Staining for Metallothionein, E-Cadherin and MCM2 significantly differed between benign neoplasm (n = 22) and thyroid-confined PTC (n = 21) (p = 0.002, 0.004 and 0.005, respectively), between benign neoplasm and PTC with extrathyroidal extension (n = 11) (p = 0.001, 0.006 and 0.01, respectively), and between benign neoplasm and PTC with metastases (n = 12) (p = 0.01, <0.001 and 0.037, respectively). No staining correlated with extrathyroidal extension. The intensity of E-Cadherin staining was significantly lower in PTC with metastases than thyroid confined PTC and PTC with extrathyroidal extension (p = 0.028 and 0.021, respectively). Conclusions: Immunohistochemical staining for Metallothionein, E-Cadherin and MCM2 significantly distinguished between benign thyroid tumor and PTC. E-Cadherin staining significantly and inversely correlated with the presence of metastases.

Keywords: extrathyroidal invasion; immunohistochemical markers; metastases; papillary thyroid carcinoma.

Figure 1

Photomicrographs of the immunohistochemical staining of MCM2 (arrows) in the different studied groups. (A), Benign neoplasm, 10% of cells stained (original magnification × 200); (B), PTC + 0, 20% of cells stained (original magnification × 200); (C), PTC + E, 25% of cells stained (original magnification × 200); (D), PTC + M, 25% of cells stained (original magnification × 200).

Figure 2

Photomicrographs of the immunohistochemical staining of NP-1 (stained in brown) in the different studied groups. Different groups had the same staining intensity (score 2). (A), Benign neoplasm (original magnification × 100); (B), PTC + 0 (original magnification × 100); (C), PTC + E, (original magnification × 100); (D), PTC + M, (original magnification × 200).

Figure 3

Photomicrographs of the immunohistochemical staining of MT (arrows) in the different studied groups, being able to differentiate benign neoplasm from all PTC groups but not between PTC groups. (A), Benign neoplasm, score 3 (original magnification × 100); (B), PTC + 0, score 1 (original magnification × 200); (C), PTC + E, score 1 (original magnification × 200); (D), PTC + M, score 1 (original magnification × 200).

Figure 4

Photomicrographs of the immunohistochemical staining of E-Cadherin (arrows) in the different studied groups, being able to differentiate between all groups. (A), benign neoplasm, score 3 (original magnification × 400); (B), PTC + 0, score 2 (original magnification × 200); (C), PTC + E, score 1 (original magnification × 400); (D), PTC + M, score 0 (original magnification × 200).