Cyclin E expression in papillary thyroid carcinoma: Relation to staging

Abstract

Cyclin E plays a pivotal role in the regulation of G1-S transition and relates to malignant transformation of the cells. However, the clinical significance of cyclin E expression in patients with papillary thyroid carcinoma (PTC) remains unknown. We examined by immunohistochemistry the expression of cyclin E in 41 resected PTCs in pathologic stages from pT1a to pT4 and analyzed its relation to clinicohistopathologic factors. The positive staining was divided into 3 grades: no expression if less than 10%, expression if 11-50% and overexpression if more than 50% of the nuclei of tumor cells were stained positively. Cylin E expressions were observed in 75.6% of analyzed PTCs but only 60% of papillary microcarcinomas (PMCs) were immunopositive for cyclin E expression. However, cyclin E staining was observed in 90.4% of PTCs in a group with TNM higher than pT1a. Key words: cyclin E; papillary thyroid carcinoma; papillary thyroid microcarcinomaSeveral clinical and histopathologic factors have been shown to be important prognostic factors for survival in papillary thyroid carcinoma (PTC). These include patient age, patient gender, tumor size, extrathyroidal extension and the presence of distant metastases. 1,2 However, there is a clinical need for a prognostic marker for thyroid papillary cancer, especially considering increasing number of diagnosed papillary thyroid microcarcinomas. 3 Papillary microcarcinomas (PMCs) of the thyroid are defined as small papillary carcinomas measuring less than 1 cm in maximum dimension. The biology of these tumors is not fully understood because, although lymph node metastases from PMCs are very uncommon on rare occasions, a PMC behaves aggressively and metastasizes early, presenting with clinically evident lymph node metastases. These tumors then result in significant morbidity and mortality. 4 At present, traditional histopathologic assessment cannot distinguish between the typical PMC, which almost always remains quiescent, and the unusual PMC, which has the potential to behave aggressively.The last decade has seen an enormous expansion in our understanding of the molecular mechanisms governing cell cycle regulation. Altered expression of cell cycle regulators and the subsequent deregulation of the cell cycle may be important steps in carcinogenesis and are the most consistently found events in human malignancies, including thyroid cancer. [5][6][7][8][9][10][11] Among the G1 cyclins, cyclin D1 and cyclin E are key regulators during the G1/S cell cycle transition, and perhaps the most important checkpoint in the mammalian cell cycle. 12 Amplification of the cyclin E gene locus was observed in several cancers, including breast, 13-16 thyroid, 8,11 colorectal, 17,18 laryngeal 19 and lung cancers. 20 -22 Furthermore, cyclin E is also altered in leukemias and lymphomas. [23][24][25] Moreover, in several studies, the cyclin E expression was associated with bad prognosis. 14 -16,19 -21,26 In 1994, Keyomarsi et al. 14 proposed cyclin E as a prognostic marker for breast cancer and in the...

Altered Expression of Cyclins and Cell Cycle Inhibitors in Papillary Thyroid Cancer: Prognostic Implications

“…One potential explanation for the discordance in both nuclear and cytoplasmic staining among studies to date could be the choice of specific antibodies. Our studies used a rabbit polyclonal antibody; previous studies in thyroid have used either 13A3 (31,35,36) or HE12 (30) monoclonal mouse antibodies. Although ours is the first report we are aware of that has utilized this antibody in IHC studies of human thyroid, it has been used in studies of human bladder (13) and breast (9,28) cancer with results similar to those obtained with mouse monoclonal antibodies.…”

Patterns of cyclin A and B1 immunostaining in papillary thyroid carcinoma

“…Previous studies by the authors of the presented study suggested that an increased expression of cyclin D, Pin 1 (peptidyl-prolyl cis/trans isomerase, which also plays a critical role in cell restriction points -particular in G1/S phase) and cyclin E, could play an important role in PTC carcinogenesis [11,12,13,14]. However, the role of other cell cycle regulatory proteins in PTC remains largely undefined.…”

“…Carcinogenesis, as a result of uncontrolled cell proliferation, may result from an increased expression of cell cycle up-regulators, such as cyclins [11].…”

Expression of Cell Cycle Biomarkers and Telomere Length in Papillary Thyroid Carcinoma: A Comparative Study Between Radiation-Associated and Spontaneous Cancers

“…36 Cytoplasmic cyclin E overexpression was already observed in breast human cell cultures. 37 In thyroid cancers, previous studies revealed conflicting results, with nuclear and cytoplasmic cyclin E stainings being either strong 18,21,27 or weak. 18,27 In our study on PTCs, we found mainly cytoplasmic cyclin E immunostaining that was more frequently found in sporadic cancers.…”

“…20 Cyclin E is overexpressed in thyroid tumors at an advanced stage, as also found in breast cancers. [21][22][23] Telomere length abnormalities seem to be one of the earliest genetic alterations of epithelial cancer cells. 24,25 Although the expression of cyclins and telomere length have already been studied in thyroid cancer tissues, 26 -29 no study has yet compared these characteristics in radiation-induced versus sporadic PTC.…”