The expression of ck-19,hbme-1, galectin-3, cox-2 and vegf in thyroid papillary carcinomas, nodular hyperplasia and well-differantiated tumors of uncertain malignant potential

THE EXPRESSION OF CK-19,HBME-1, GALECTIN-3, COX-2 AND VEGF IN THYROID PAPILLARY CARCINOMAS, NODULAR HYPERPLASIA AND WELL-DIFFERANTIATED TUMORS OF UNCERTAIN MALIGNANT POTENTIAL Objective: Thyroid carcinomas are the most frequent malignancies of the endocrine system. There is a significant increase in the incidence of papillary thyroid cancers recently. Histological types of the benign and malign thyroid epithelial tumors have similar morphological features causing problems in differential diagnosis and diagnostic disagreement between pathologists. Thus immunohistochemical markers are needed to contribute in histological diagnosis and their usefulness in routine practice is still being researched. In our study we evaluated immunoreactivities of CK19, HBME-1, galectin-3, COX-2 and VEGF in nodular hyperplasia, well-differentiated tumor of uncertain malignant potential, papillary microcarcinoma and papillary carcinoma. Material and Methods: 97 cases were evaluated retrospectively in 4 groups, involving 30 cases of nodular hyperplasia, 7 cases of well-differentiated tumor of uncertain malignant potential, 30 cases of papillary microcarcinoma (classic and follicular variant) and 30 cases of papillary carcinoma (classic and follicular variant), which were diagnosed at Afyon Kocatepe University, Hospital of Medical Faculty, Department of Pathology, between January 2002 and July 2012. Gender, age, tumor diameter, tumor type (classic-follicular), multifocality, capsular invasion and vascular invasion status of the cases were identified. 164 blocks were selected involving one block from each case of nodular hyperplasia and two blocks (one from the tumor and one from the opposite non-tumoral lobe) from each case of well-differentiated tumor of uncertain malignant potential, papillary microcarcinoma and papillary carcinoma. Sections of these blocks were stained with CK-19, HBME-1, galectin-3, COX-2 and VEGF using immunohistochemical methods. Features of staining were evaluated and scored according to the extent and intensity. Results: Papillary carcinoma and papillary microcarcinoma showed significantly higher CK-19, HBME-1, galectin-3, VEGF expression compared to nodular hyperplasia (p<0,05). Tumoral areas of the papillary carcinoma showed significantly higher CK-19, HBME-1, galectin-3, COX-2 and VEGF expression, and tumoral areas of the papillary microcarcinoma showed significantly higher CK-19, HBME-1, galectin-3 and VEGF expression than that of extratumoral areas (p<0,05). Classic type of papillary carcinoma and papillary microcarcinoma showed higher CK-19, HBME-1, galectin-3 and VEGF expression compared to the follicular type (p<0,05). Well-differentiated tumor of uncertain malignant potential showed higher CK-19 and HBME-1 expression than nodular hyperplasia; lower HBME-1 and VEGF expression than papillary microcarcinoma and papillary carcinoma; lower galectin-3 expression than papillary microcarcinoma, and these differences were statistically significant (p<0,05). However, there was no statistically significant difference in expression of all the markers we have studied between tumoral and extratumoral areas in this group (p>0,05). Conclusion: CK-19, HBME-1, galectin-3, COX-2 and VEGF may serve as useful immunohistochemical markers for diagnosis of papillary carcinoma and papillary microcarcinoma. We have observed significantly higher CK-19, HBME-1, galectin-3 and VEGF expression in papillary carcinoma and papillary microcarcinoma compared to nodular hyperplasia; suggesting that these markers may be more useful for supporting the diagnosis. We have observed significantly higher CK-19, HBME-1, galectin-3, COX-2 and VEGF expression in papillary carcinoma, and CK-19, HBME-1, galectin-3 and VEGF expression in papillary microcarcinoma in tumoral areas than that of extratumoral areas, supporting the idea that these markers may be useful for diagnosis of papillary carcinoma and papillary microcarcinoma. Classic type of papillary carcinoma and papillary microcarcinoma showed higher CK-19, HBME-1, galectin-3 and VEGF expression compared to the follicular type. These markers may be useful especially for diagnosis of malignant tumors with papillary morphology. We have observed that well-differentiated tumor of uncertain malignant potential showed significantly higher CK-19 and HBME-1 expression than nodular hyperplasia; suggesting that these markers may be useful for differential diagnosis of equivocal nodules. However, there was no statistically significant difference between tumoral and extratumoral areas in this group for expression of all the markers we have studied. Immunohistochemical markers may have a supplementary role for diagnosis of papillary carcinoma and papillary microcarcinoma in equivocal nodules, however in our opinion they cannot be used alone for diagnosis in the absence of nuclear criteria. In our study we had very limited number of cases for well-differentiated tumor of uncertain malignant potential, thus further immunohistochemical studies in larger series is needeed to clarify this subject.