Patterns of cyclin E, retinoblastoma protein, and p21Cip1/WAF1 immunostaining in the oncogenesis of papillary thyroid carcinoma

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 clinicohistopatbologic 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 (PNC)] 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.