Patterns of Cyclin E, Retinoblastoma Protein, and p21Cip1/WAF1 Immunostaining in the Oncogenesis of Papillary Thyroid Carcinoma

• Published in: Clinical cancer research 2005-02, Vol.11 (3), p.1037-1043
• Main Authors: BRZEZINSKI, Jan, MIGODZINSKI, Adam, TOCZEK, Aleksandra, TAZBIR, Jozef, DEDECJUS, Marek
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Carcinoma, Papillary - metabolism; Carcinoma, Papillary - pathology; Cell Cycle Proteins - analysis; cell cycle regulatory proteins; Cyclin E - analysis; Cyclin-Dependent Kinase Inhibitor p21; Endocrinopathies; Humans; Immunohistochemistry; Medical sciences; Non tumoral diseases. Target tissue resistance. Benign neoplasms; papillary thyroid microcarcinoma; Pharmacology. Drug treatments; Retinoblastoma Protein - analysis; Thyroid Gland - chemistry; Thyroid Gland - pathology; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases)
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.1037.11.3

Purpose: Uncontrolled cell proliferation, a hallmark of cancer, may result from an increased expression of cell cycle up-regulators, and/or from a reduced expression of cell cycle down-regulators. In the present study, we analyzed, by immunohistochemistry, the expression of a panel of three proteins: cyclin E and two cell cycle inhibitors, p21 Cip1/WAF1 and retinoblastoma protein (pRb) product, in different stages of papillary thyroid carcinomas (PTC). Experimental Design: We investigated immunostaining patterns of the proteins in question in 51 resected PTC in pathologic stages, ranging from pT 1a to pT 4 , taking into consideration their relation to clinicohistopathologic factors. Results: We observed a significant, progressive loss of expression of p21 Cip1/WAF1 with advancing tumor grade. The differences reached values of significance between pT 1a [papillary thyroid microcarcinomas (PMC)] and pT 2 and between PMC and pT 4 stages of PTC. pRb presented a similar immunostaining pattern to that of p21 Cip1/WAF1 and the differences reached values of significance between pT 1a and pT 2 , and between PMC and pT 4 stages of PTC. The results of cyclin E immunostaining corresponded to our recently published result, and a negative correlation was observed between the immunostaining index of cyclin E and pRb. Conclusions: The results of the present study suggest that cyclin E expression and suppression of pRb and p21 Cip1/WAF1 may be characteristic patterns of immunostaining for PTC with a tendency to early metastasizing. If our results are confirmed in a larger study, the diagnostic panel, constructed of the antibodies against these proteins, may become a valuable tool in predicting the metastatic potential in PTC.