Expression And Clinical Significance Of EGFR,TGF-a And PCNA Protein In Papillary Thyroid Carcinoma

Thyroid carcinoma is one of the common head and neck carcinomas, Papillary thyroid carcinoma is about 70%-80% in thyroid carcinoma. The five-years survival rate is higher after operation, but they trend metastasis of lymph node, then increase the difficulties of operation and the occurrence rate of the thyroid neoplasm tends to ascend in recent years, So it is important of finding the biological parameter to prognosticate the degree of metastasis and prognosis.The epidermal growth factor receptor and its ligand are the important signal systems that regulate normal cell growth. Abnormal expression of the epidermal growth factor receptor and its ligand has been associated with malignant transformation. They have been referred to as autocrine growth stimulation and play an important role in the development and progression of tumors.Family of epidermal growth factor receptor includes c-erbB-1, c-erB-2, c-erB-3 and c-erB-4.EGFR is glycoprotein encoded by c-erbB-1.EGFR is distributed on epithelial cell of mammal. The single transmembrane sequence separates the domain of integrating ligand and the domain of tyrosine protein kinase. The activities of tyrosine protein kinase play an important role in cell proliferation. The domain of integrating ligand binds with two molecule can actives tyrosine protein kinase and increase genetic transcription.TGF-αbelongs to family of epidermal growth factor receptor. It can be synthesized in human and mammal. It affects tissue and organ by autocrine,paracrine and endocrine. TGF-αgains self-stimulation function of growth by autocrine. That can partially explain the indeterminate growth of tumor cell and can be called intracrine loop. Paracrine is that cell secretes regulatory peptide and affect vicinity cells. It tends to form larger tumour and metabasis of tumor. TGF-αalso has the function of endocrine.PCNA is an accessory protein. It exists in the cell nucleus and only is expressed in proliferation cell. It plays an important role in synthesis of PCNA. When the duplicating of PCNA accelerates, the expression of PCNA is higher, so it is an endogenous marker reflecting growing of cell. PCNA has visible periodicity in proliferation cell.Now to detect the expression of EGFR,TGF-αand PCNA protein in Papillary thyroid carcinoma(PTC) and investigate theirs' relationship with development invasiveness and metastasis of the tumor.Material and methodsWe have collected 82 specimens from surgical resections during 2005 year. All the sections have detailed clinical data and they were affirmed by pathologists. All the cases were not performed any chemotherapy, radiotherapy and immunization therapy before operation. There is 47 cases for papillary thyroid carcinoma, with metastasis of lymph node 24 examples, without metastasis of lymph node 23 examples, 10 male, 37 female, age between 13 to 72years old, average age is 41.68±14.57, thyroid adenoma 20 examples and normal thyroid tissue 15 examples. The histological type and grade were assigned with the use of UICC, 29 cases had stageⅠ,12 stageⅡ, 5 stageⅢand 1 stageⅣ. By using immunohistochemical SP method detect the expression of EGFR,TGF-a and PCNA protein in all tissues. Control sections with negative expression of EGFR,TGF-a and PCNA were incubated with PBS. Meanwhile, we used Papillary thyroid carcinoma sections as control group with positive expression of EGFR,TGF-a and PCNA. Statistical analysis was performed using test and P value less than 0.05 were considered significant.Results 1.The expression of EGFR,TGF-a and PCNA in PTC, thyroid adenoma and normal thyroid gland tissueThe expression of EGFR is orientated as the cytoplasm and cytomembrane. The positive rate of EGFR is 59.57% in papillary carcinoma, notably higher than25% in thyroid adenoma and 6.67%in normal thyroid tissues (P<0.05). The expression of TGF-a is orientated as the cytoplasm. The positive rate of TGF-a is 55.32% in papillary carcinoma, notably higher than20% in thyroid adenoma and 13.33%in normal thyroid tissues (P<0.05). The expression of PCNA is orientated as the cytoblast. The positive rate of PCNA is 74.47% in papillary carcinoma, notably higher than45% in thyroid adenoma and 13.33%in normal thyroid tissues (P<0.05). The result shows that the expression of EGFR,TGF-a and PCNA protein in papillary carcinomas is significantly higher than others.2.The relationship between the expression of EGFR,TGF-a and PCNA ,clinical data and pathology characterThere is no obvious relationship among age,sex and TNM of the positive expression of EGFR(P>0.05), but there is obviious relationship between the degree of infiltration and metastasis of lymph node(P<0.05). There is no obvious relationship among age,sex,TNM and the degree of infiltration of the positive expression of TGF-a (P>0.05), but there is obvious relationship of metastasis of lymph node(P<0.05). There is no obvious relationship among age,sex,TNM and the degree of infiltration of the positive expression of PCNA(P>0.05), but there is obvious relationship of metastasis of lymph node(P<0.05).3.Relationship among EGFR,TGF-a and PCNAThe positive rate of papillary carcinoma with metastasis of lymph node in the both expression of EGFR and TGF-a is 84.21%; The positive rate of papillary carcinoma with metastasis of lymph node in the neither expression of EGFR and TGF-a or either expression of EGFR and TGF-a is 46.15%. They have the significant difference (P<0.05).The correlation between the expression of EGFR and PCNA in papillary carcinomas: 28 aberrant expression of EGFR in PTC have appeared 27 positive expression of PCNA. The aberrant expression of EGFR is significant correlated to the expression of PCNA (P<0.05). The correlation between the expression of TGF-a and PCNA in papillary carcinomas: 26 aberrant expression of TGF-a in PTC have appeared 24 positive expression of PCNA. The aberrant expression of TGF-a is significant correlated to the expression of PCNA (P<0.05).ConclusionAccording the expression of EGFR,TGF-a and PCNA protein in several kinds of Histology classifications of thyroid we have found that:1.The high expression of EGFR,TGF-a and PCNA in papillary carcinomas relate to the development and progression of papillary carcinomas.2.The high expression of both EGFR and TGF-a protein relate to the metastasis of lymph node. EGFR,TGF-a may form an autocrine growth loop on the surface of thyroid cancer cells.3.A positive correlation is observed among EGFR,TGF-a and PCNA expression. They probably play a cooperation role in tumor genesis.4.To detect the expression of EGFR,TGF-a and PCNA protein in the samples by puncturing, it may be an useful method to early diagnose the thyroid carcinomas.5.The activities of RTK may play an important role in tumor genesis, the inhibitors to aim the target of EGFR can interrupt the EGFR' s function, they may be a useful method to treat papillary thyroid carcinoma.