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Patterns of Cyclin E, Retinoblastoma Protein, and p21^Cip1/WAF1 Immunostaining in the Oncogenesis of Papillary Thyroid Carcinoma

Jan Brzeziski¹, Adam Migodziski², Aleksandra Toczek³, Józef Tazbir² and Marek Dedecjus¹

¹ Department of Endocrinological and General Surgery, Institute of Endocrinology, Medical University of ód; Departments of ² General and Vascular Surgery and Emergency Medicine, Medical University of ód, The M. Kopernik Memorial Hospital, ód, Poland and ³ Cardiological and Transplantological Immunology, The M. Kopernik Memorial Hospital, ód, Poland

Requests for reprints: Jan Brzeziski, Department of Endocrinological and General Surgery, Institute of Endocrinology, Medical University of ód, ul. Pabianicka 62, 93-513 ód, Poland. Phone: 48-42-689-5171; Fax: 48-42-689-5172; E-mail: mdedecjus{at}poczta.wp.pl.

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 pT₄, 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 pT₂ and between PMC and pT₄ 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 pT₂, and between PMC and pT₄ 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.

Key Words: cell cycle regulatory proteins • immunohistochemistry • papillary thyroid microcarcinoma