Elsevier

Surgery

Volume 140, Issue 6, December 2006, Pages 899-906
Surgery

American Association of Endocrine Surgeons
Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression

Presented at the 27th Annual Meeting of the American Association of Endocrine Surgeons, New York, New York, May, 2006.
https://doi.org/10.1016/j.surg.2006.07.027Get rights and content

Background

Genetic screening studies suggest that genetic changes underlie progression from well differentiated to anaplastic thyroid cancers. The aim of this study is to determine to what extent cell cycle/apoptosis regulators contribute to cancer progression.

Methods

Tissue microarrarys (TMAs) were constructed from well-differentiated papillary thyroid carcinoma (WDPTC; n = 41), poorly differentiated thyroid carcinoma (PDTC; n = 43), and anaplastic thyroid carcinoma (ATC; n = 22). TMAs were immunostained for 7 different cell cycle/apoptosis–related genes (p53, Ki-67, bcl-2, mdm-2, cyclin D1, p21, and p27).

Results

p53 (0%, 12%, 32%) and Ki-67 (5%, 49%, 82%) were expressed with increasing frequency, and bcl-2 (68%, 42%, 0%) and p21 (40%, 7%, 0%) with decreasing frequency in WDPTC to PDTC and ATC, respectively (P < .001). Interestingly, mdm-2 (54%, 5%, 0%) showed decreased expression along the progression axis (P < .001). p27 and cyclin D1 were expressed in <15% of cases, with a trend toward decreasing expression from WDPTC to PDTC to ATC.

Conclusions

These data confirm the presence of increasing genetic complexity with progressive dedifferentiation in thyroid cancer, with aberrant tumor suppressor activity and increased proliferative activity being most prevalent in ATC. The data also confirm the intermediate position of PDTC in the classification scheme of thyroid carcinomas.

Section snippets

Specimens

A total of 41 WDPTC, 43 PDTC, and 22 ATC specimens were selected from the Memorial Sloan-Kettering Cancer Center (MSKCC) Pathology Database. The specimens were reviewed by our endocrine pathologist (R.A.G.) to ensure proper histologic diagnosis. PTC included papillary thyroid cancers displaying “ground glass” nuclei (“Orphan Annie eye” nuclei) without a significant degree of mitotic activity, necrosis, or nuclear pleomorphism. Only classical and follicular variants of papillary carcinoma were

Ki-67 expression

Only 2 (5.4%) of 37 WDPTC overexpressed Ki-67, whereas 21 (48.8%) of 43 PDTC and 18 (81.8%) of 22 ATC were Ki-67 positive. All aspects of this increase in Ki-67 were statistically significant, WDPTC versus PDTC or ATC (P < .0001) and PDTC versus ATC (P = .015) (Fig 1).

p53 expression

None of the 37 WDPTC expressed p53, whereas 5 (11.6%) of 43 PDTC and 7 (31.8%) of 22 ATC were p53 positive. In regard to p53 overexpression, there was a statistically borderline significant correlation between WDPTC versus PDTC (P

Discussion

This study was undertaken to further our understanding of thyroid carcinoma progression at the molecular level with the hope of identifying useful diagnostic and therapeutic markers. For this purpose, we studied a cohort of pathologically well-characterized thyroid carcinomas of follicular cell origin encountered at a single institution. Because the histopathologic definition of certain thyroid tumors (such as PDTC) can vary, all cases included in this study were subjected to a standardized

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