Expression Of CK19, PCNA, VEGF, And TTF-1 In Thyroid Follicuylar Tumors

Thyroid follcular carcinoma is the second most common thyroid cancers in which the most common type is thyroid papillary carcinoma. Thyroid follcular carcinoma is accounting for 15-20% of all thyroid cancers. It is highly malignant and numerous cases of follcular thyroid cancer are subclinical at the early stage of the disease. Vascular invasion is characteristic to follicular carcinoma and it is prone to spread through blood stream to other distant organs of the body, correlating with a poor prognosis.Sometime it's hard to distinguish reliably between well differentiated follicular carcinoma and follicular adenoma basing on the pathomorphology, leading to misdiagnosis. Actually, the fact that the pathomorphology based differential diagnosis is always a clinical failure between follicular carcinoma and follicular adenoma makes it necessary and urgent for pathologist to seek other assessment approaches to assist in the differential diagnosis.Immunohistochemistry staining for the protein markers which are exclusively or preferentially present in follicular carcinoma or follicular adenoma, as far as concerned, is the leading assistant assessment to the differential diagnosis. We detected the immunoexpression profiles of CK19, PCNA, VEGF and TTF-1 in follicular carcinoma sections and follicular adenoma sections, aiming to investigate the value of those combined protein markers in the differential diagnosis between the two types of thyroid lesions. CK19, a keratin with a low molecular weight of 40kD, is the smallest member of the keratin family. It is widely expressed in the simple epithelium including mesothelium, and the location is mainly confined to cytoplasm. The value of CK19 in the differential diagnosis in thyroid lesions especially between papillary hyperplasia and papillocarcinoma is widely recognized.PCNA is a cyclin, and its dynamic expression alteration correlates with that of DNA content during the cell cycle. It is correlated with the cell proliferation and it is able to function as an endogenous marker or indicator for the cell proliferation rate, thus highly correlating with the tumor cell proliferation potential, metastasis and prognosis. PCNA is widely involved in the researches on different kinds of carcinomas like gastric carcinoma, pulmonary carcinoma, hepatoma, colorectal carcinoma and endometrial carcinoma.Vascular endothelial growth factor (VEGF) stimulates endothelial cell proliferation, migration, and plays an important role in tumor vascularization through paracrine secretion. It also enhances vascular permeability and promotes the infiltration of mononuclear cell, fibroblast and endothelial cell, facilitating the induction of tumor matrix formation and the vascular invasion and eventually promoting tumor metastasis.Thyroid transcription factor-1 (TTF-1) is a member of Nkx-2 family, sharing the homeodomain of intranuclear transcription factors. It regulates transcription of genes specific for the thyroid, lung, and diencephalon. It is also known as thyroid specific enhancer binding protein (T/EBP). It is used in anatomic pathology as a marker to determine if a tumor arises from the lung or thyroid. In the thyroid, follicular and parafollicular cells are positive for TTF-1.Immunohistochemistry is applied to detect the expression profiles of CK19,PCNA,VEGF and TTF-1 in 26 cases of follicular carcinoma and 41 cases of follicular adenoma, aiming to estimate the value of those four markers on the differential diagnosis between follicular carcinoma and follicular adenoma.Results:Granular cytoplasmic staining of CK19 is considered to be positive. The positive expression rate of CK19 is high in follicular carcinoma tissues, with a positive percentage of 92.31%(24 cases are positive staining out of the total 26 cases). However, in follicular adenoma tissues, the positive expression rate of CK19 is strikingly low compared to that in follicular carcinoma tissues, with a positive percentage of 7.69%(3 cases are positive staining out of the total 41cases. On the basis of these experiments we conclude that immnunostaining of CK19 is beneficial to the differential diagnosis between follicular carcinoma and follicular adenoma.PCNA shows diffuse or granular nuclear staining and the granular nuclear staining is considered to be positive. The positive expression rates of PCNA in follicular carcinoma sections and follicular adenoma sections are 39.62%～88.57% and 2.61%～19.60% respectively. The proliferation indexes in follicular carcinoma sections and follicular adenoma sections are 70.96%±11.7% and 7.05%±0.43% respectively. It indicates that PCNA is of a high positive expression rate in follicular carcinoma wile with a low one in follicular adenoma, and that PCNA can be used as a sensitive marker in assisting in the differential diagnosis between follicular carcinoma and follicular adenoma.VEGF locates in cytoplasm or on the cell membrane and the granular staining is considered to be positive. The positive expression rates of VEGF in follicular carcinoma and follicular adenoma are 65.38%(17 positive cases of total 26 cases)and 21.95%(9 positive cases of total 41 cases)respectively. It means that VEGF is highly expressed in follicular carcinoma while its expression in follicular adenoma is low. On the basis of these experiments we conclude that VEGF, one of the most important angiogenesis promoting factors, play its crucial role in the transformation and progression of follicular carcinoma.We detect the expression of TTF-1 by a quantitative method and find that TTF-1 locates in the nuclei in both follicular carcinoma sections and follicular adenoma sections. The PU values of TTF-1 in follicular carcinoma sections and follicular adenoma sections are 14.9%±2.4% and 16.1%±1.3% respectively. It suggests that the TTF-1 is expressed in both follicular carcinoma and follicular adenoma, and with no significant difference in positive expression rate. On the basis of these experiments we conclude that TTF-1 is not beneficial to the differential diagnosis between follicular carcinoma and follicular adenoma.Collectively, the combined detection of CK19,PCNA,VEGF is beneficial to the differential diagnosis between follicular carcinoma and follicular adenoma while TTF-1 can't assist in differential diagnosis. However, it can be used in anatomic pathology as a marker to determine if a tumor arises from the thyroid.