Expression of CK-19, cErbB2, galectin-3, and p53 in papillary thyroid carcinomas

Amaç: Bu çalışmada papiller tiroid karsinomlarında CK-19, cErbB2, galectin-3 ve p53 ekspresyonu araştırıldı. Yöntem ve gereç: Çalışmaya dahil edilen 23 papiller karsinom (PK) ve 20 papiller mikrokarsinom (PMK) olgusuna immünhistokimya uygulandı. Boyanma yaygınlığı ve yoğunluğu semikantitatif olarak değerlendirildi. Bulgular: PK olgularının % 56,5’ i ve PMK olgularının % 15,0’ i cErbB2 ile güçlü immünreaksiyon gösterdi. Galectin- 3 ile PK olgularının % 47,8’ inde boyanma yaygınlığı skoru 2+ iken, PMK olgularında bu oran % 10,0 idi (P = 0,003). PMK olgularının tamamı ile PK olgularının 21’ inde değişken yaygınlıkta CK-19 ekspresyonu gözlendi. p53 ile nükleer boyanma saptanmazken PK olgularının % 65,2’sinde ve PMK olgularının % 55,0’inde sitoplazmik immünreaksiyon gözlendi.Sonuç: Hem PK hem de PMK olgularının benzer yaygınlık ve yoğunlukta CK-19 ekspresyonu göstermesi, papiller karsinomun saptanmasında bu markırın yardımcı olabileceğini düşündürür. PK olgularının çoğunluğunda yaygın ve güçlü galectin-3 ekspresyonu, cErbB2 ile bu olguların güçlü immünreaksiyon göstermesi ve PMK olgularında daha az yaygın olan zayıf boyanma, bu boyanmaların tümör boyutu ile ilişkili olabileceğini akla getirir. Toplam 43 papiller karsinomun hiçbirinde p53 ile nükleer immünreaksiyon gözlenmemesi, p53’ün tiroid karsinogenezisinde daha ileri basamaklarda rol aldığı görüşünü desteklemektedir.

Papiller tiroid karsinomlarında CK-19, cErb B2, galectin-3 ve p53 ekspresyonu

Aim: To determine the immunohistochemical expression of CK-19, cErbB2, galectin-3, and p53 in papillary thyroid carcinomas (PTC).Materials and methods: In this study immunohistochemistry was performed on 23 papillary carcinomas (PCs) and 20 papillary microcarcinomas (PMCs). The extents of staining and intensity were scored semiquantitatively.Results: Of the PC cases 56.5% and of the PMC cases 15.0% were stained strongly by cErbB2. The extent of 2+ staining by galectin-3 was 47.8% in PC, whereas it was only 10.0% in PMC (P=0.003). All PMC cases were stained by CK-19 and 21 cases of PC expressed positivity in varying extent of staining. No nuclear immunostaining was detected by p53 in PC and PMC. However, 65.2% of PC and 55.0% of PMC cases showed cytoplasmic reactivity.Conclusion: Both PC and PMC cases showed similar staining extent and intensity by CK-19. This may conclusively help in identifying the papillary carcinoma cases. The majority of PCs stained diffusely and strongly by galectin-3 and expressed strong reaction by cErbB2, which might suggest a relation with the size of the tumor as PMCs stained less diffusely and strongly. As no nuclear staining was detected by p53 in 43 papillary carcinomas, we support the idea that p53 expression is a late event in thyroid carcinogenesis.

PDF

___

1. Cheung CC, Ezzat S, Freeman JL, Rosen IB, Asa SL. Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol 2001; 14(4): 338-342.
2. Khurana KK, Truong LD, LiVolsi VA, Baloch ZW. Cytokeratin-19 immunolocalization in cell block preparation of thyroid aspirates. An adjunct to ine-needle aspiration diagnosis of papillary thyroid carcinoma. Arch Pathol Lab Med 2003; 127(5): 579-583.
3. Nasır MR, Mukhopadhyay S, Zhang S, Katzenstein AL. Immunohistochemical markers in diagnosis of papillary thyroid carcinoma: Utility of HMBE-1 combined with CK-19 immunostaining. Mod Pathol 2006; 19(12): 1631-1637.
4. Utrilla JC, Lacave IM, San Martin MV, Fernandez- Santos JM, Davidson GH. Expression of c- erbB2 oncoprotein in human thyroid tumours. Histopathology 1999; 34: 60- 65.
5. Ensinger C, Prommegger R, Kendler D, Gabriel M, Spizzo G. Her2/ neu expression in poorly- diferentiated and anaplastic thyroid carcinomas. Anticancer Research 2003; 23: 2349-2354.
6. Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, Chapelle A. Galectin-3, ibronectin-1, CITED-1, HMBE-1 and cytokeratin- 19 immunohistochemistry is useful for the diferential diagnosis of thyroid tumors. Mod Pathol 2005; 18: 48-57.
7. de Matos PS, Ferreira AP, de Oliveiria Facuri F, Assumpcao LV, Metze K, Ward LS. Usefulness of HMBE-1, cytokeratin-19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology 2005; 47(4): 391-401.
8. Zafon C, Obilos G, Castellvi J, Tallada N, Baena JA. Clinical signiicance of RET/PTC and p53 protein expression in sporadic papillary thyroid carcinoma. Histopathology 2007; 50: 225-231.
9. Lemoine NR, Wyllie FS, Lillehaug JR, Staddon SL, Hughes CM, Aasland R, Shaw J, Varhaug JE, Brown CL and Gullic WJ. Absence of abnormalities of the cErbB1 and cErbB2 protooncogenes in human thyroid neoplasia. Eur J Cancer 1990; 26: 777-779.
10. Sugg SL, Ezzat S, Zeng L, Rosen IB, Freeman JR, Asa SL. Cytoplasmic staining of erbb-2 but not mRNA level correlates with diferentiation in human thyroid neoplasia. Clin Endocrinol (Oxf). 1998 Nov; 49(5): 629-37.
11. Aksalen LA, Varhaug JE. Oncoproteins and tumor progression in papillary thyroid carcinoma: presence of epidermal growth factor reseptor, c-erbB-2 protein, estrogen reseptor related protein, p21-ras protein, and proliferation indicators in relations to tumor recurrences and patient survival. Cancer 1995; 76: 1643-1654.
12. Haugen DR, Akslen LA, Varhaug JE, Lillehaug JR. Expression of c-erbB-2 protein in papillary thyroid carcinomas. Br J Cancer. 1992 Jun; 65(6): 832-7.
13. Cvejic D, Savin S, Petrovic I, Paunovic I, Tatic S. Galectin-3 expression in papillary microcarcinoma of the thyroid. Histopathology 2005; 47(2): 209-214.
14. Hermann S, Sturm I, Mrozek A, Klosterhalfen B, Hauptmann S, Dörken B. BAX expression in benign and malignant thyroid tumours: dysregulation of wild-type p53 is associated with a high BAX and p21 expression in thyroid carcinoma. Int J Cancer 2001; 92: 805-811.