Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024;39(3):211-221.
doi: 10.3233/CBM-230230.

Diagnostic and prognostic utility of TROP-2, SLP-2, and CXCL12 expression in papillary thyroid carcinoma

Amany Selim Attia  1 , Samia Hussein  2 , Hend Sameh  2 , Amr Khalil  3 , Ahmad Barakat Waley  4 , Ihab Matar  5 , Reham Sameh  1
Affiliations

Diagnostic and prognostic utility of TROP-2, SLP-2, and CXCL12 expression in papillary thyroid carcinoma

Amany Selim Attia et al. Cancer Biomark. 2024.

Abstract

Background: Papillary thyroid carcinoma (PTC) is the most frequent thyroid malignancy. Histopathological examination is widely accepted as the gold standard test for the diagnosis of PTC. However, the histopathological examination sometimes can't differentiate PTC from other thyroid diseases. Differentiating PTC from other thyroid diseases is essential for a therapeutic approach and prognosis.

Objectives: The current study was performed to investigate the utility of TROP-2, SPL-2, and CXCL12 mRNA and protein expression in discriminating PTC from other thyroid diseases that mimic PTC.

Methods: The current study was performed on 75 cases of surgically resected thyroid glands. The cases were distributed in two groups: the PTC group and the non-PTC group. The PTC group consisted of 35 cases (25 patients of the classic PTC variant and 10 patients of the PTC follicular variant). The non-PTC group consisted of 40 cases (10 cases were multinodular goiter, 5 cases were Graves' disease, 5 cases were Hashimoto thyroiditis, 15 patients were follicular adenoma (FA) and 5 cases were follicular carcinoma). TROP-2, SPL-2, and CXCL12 mRNA expression were estimated by qRT-PCR, and protein expression was estimated by immunohistochemistry.

Results: There were upregulated TROP-2, SPL-2, and CXCL12 mRNA and protein expressions in PTC compared to non-PTC (P< 0.001, for each). There was a statistically significant upregulation in the mRNA expression of the three genes among PTC cases with larger tumor sizes (P< 0.001, for each), those with tumor stages III and IV (P= 0.008, 0.002 and < 0.001 respectively), and those with LN metastasis (P< 0.001, for each). Moreover, there was a statistically significant upregulation in CXCL-12 gene expression among PTC cases with extra-thyroid extension (P< 0.001).

Conclusion: mRNA expression of TROP-2, SPL-2, and CXCL12 among PTC cases increased in larger tumor size, tumor stages III and IV, and LN metastasis. Moreover, there was an increase in CXCL-12 gene expression among PTC cases with extra-thyroid extension. Thus, TROP-2, SPL-2, and CXCL12 expressions could be possible diagnostic and prognostic markers in PTC.

Keywords: CXCL12; SPL-2; TROP-2; papillary thyroid carcinoma.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Figure 1.
Figure 1.
(A) PTC: papillary projections with nuclear features of PTC (X 200), (B) FVPTC: capsulated tumor with prominent nuclear features of PTC (X200), (C) Colloid goiter: variable sized follicles with flat lining (X100), (D) Graves’ disease: hyperplastic thyroid follicles with papillary projections (X200), (E) Hashimoto thyroiditis: prominent lymphoid follicles with abundant hurthle cells (X100), (F) follicular adenoma with intact capsule (X100), (G) Follicular carcinoma; thickened capsule with full thickness penetration (X100), (H) Follicular carcinoma with prominent atypia and mitosis (X200).
Figure 2.
Figure 2.
TROP2 immunostaining: (A) PTC positive membranous staining (x400), (B) FVPTC: positive membranous staining (x200), (C) Colloid goiter: negative (x200), (D) Graves’ disease with papillary hyperplasia-negative (x400), (E) Hashimoto negative (x100), (F) Follicular adenoma negative (x200), (G) Follicular carcinoma negative (x200).
Figure 3.
Figure 3.
SLP2 immunostaining: (A) PTC positive cytoplasmic staining (x200), (B) FVPTC: positive cytoplasmic staining (x200), (C) Colloid goiter: negative (x200), (D) Graves’ disease with papillary hyperplasia-negative (x200), (E) Hashimoto negative (x200), (F) Follicular adenoma negative (x200), (G) Follicular carcinoma negative (x200).
Figure 4.
Figure 4.
CXCL2 immunostaining: (A) PTC positive cytoplasmic staining (x400), (B) FVPTC: positive cytoplasmic staining (x200), (C) Colloid goitre: negative (x200), (D) Graves’ disease with papillary hyperplasia-negative (x200), (E) Hashimoto negative (x200), (F) Follicular adenoma negative (x200), (G) Follicular carcinoma negative (x200).
Figure 5.
Figure 5.
Receiver Operator Curve (ROC) for TROP2, SLP2 and CXCL2.
See this image and copyright information in PMC

References

    1. Yang X., Hu Y., Shi H., Zhang C., Wang Z. et al., The diagnostic value of TROP-2, SLP-2 and CD56 expression in papillary thyroid carcinoma, European Archives of Oto-Rhino-Laryngology 275 (2018), 2127–2134. doi: 10.1007/s00405-018-5045-x. - DOI - PubMed
    1. Mokhtar N., Salama A., Badawy O., Khoshed E. and Mohamed G., Cancer Pathology Registry 2000–2011, Cairo [Egypt], Malignant endocrine system tumors, eds.: Cairo Press, 2015, 182–192.
    1. Abdou A., Shabaan M., Abdallha R. and Nabil N., Diagnostic value of TROP-2 and CK19 expression in papillary thyroid carcinoma in both surgical and cytological specimens, Clinical Pathology 12 (2019), 1–16. doi: 10.1177/2632010X19863047. - DOI - PMC - PubMed
    1. Lin J.C., Wu Y.Y., Wu J.Y., Lin T.C., Wu C.T., Chang Y.L., Jou Y.S., Hong T.M. and Yang P.C., TROP2 is epigenetically inactivated and modulates IGF-1R signalling in lung adenocarcinoma, EMBO Mol Med 4(6) (2012), 472–485. - PMC - PubMed
    1. Trerotola M., Cantanelli P., Guerra E., Tripaldi R., Aloisi A.L., Bonasera V., Lattanzio R., de Lange R., Weidle U.H., Piantelli M. et al., Upregulation of Trop-2 quantitatively stimulates human cancer growth, Oncogene 32(2) (2013), 222–233. - PubMed