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


METHODS
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.
Brzeziński
Jan
J
Department of Endocrinological and General Surgery, Institute of Endocrinology, Medical University of Łódź, ul. Pabianicka 62, 93-513 Łódź, Poland.
Migodziński
Adam
A
Toczek
Aleksandra
A
Tazbir
Józef
J
Dedecjus
Marek
M
D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000032:analysis*; D019927:Cyclin E / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006801:Humans; D007150:Immunohistochemistry; D016160:Retinoblastoma Protein / Q000032:analysis; D013961:Thyroid Gland / Q000737:chemistry / Q000473:pathology; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein