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Updated: Aug 8, 2026
An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
Cold thyroid nodules show a marked increase in proliferation markers
Knut Krohn1, Ingo Stricker, Peter Emmrich
1III Medical Department, and Interdisciplinary Centre for Clinical Research, University of Leipzig, Leipzig, Germany.
Insights
Thyroid nodules, often found in iodine-deficient areas, show increased cell proliferation. This study found higher levels of proliferation markers (PCNA and Ki-67) in cold thyroid nodules, indicating a common feature of these growths.
Area of Science:
- Endocrinology
- Oncology
- Pathology
Background:
- Thyroid follicular adenomas and nodules are common, especially in iodine-deficient regions.
- These nodules can be hypofunctioning (cold) or hyperfunctioning (hot).
- Their clonal origin suggests increased cell proliferation is involved.
Purpose of the Study:
- To investigate if increased cell proliferation is detectable in cold thyroid nodules.
- To evaluate the expression of proliferation markers PCNA and Ki-67 in cold nodules.
Main Methods:
- Studied paraffin-embedded tissues from 40 cold thyroid nodules and surrounding normal tissue.
- Assessed proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1 antibody) expression.
- Calculated the labeling index for nodular and surrounding tissues.
Main Results:
- A significant increase in PCNA labeling index was found in 33 out of 40 cold nodules.
- A significant increase in Ki-67 labeling index was detected in 19 out of 40 cold nodules.
- Surrounding tissues with lymphocyte infiltration showed higher proliferation marker indices.
Conclusions:
- Increased thyroid epithelial cell proliferation is a common feature in most cold thyroid nodules.
- The observed proliferation marker heterogeneity did not correlate with histopathological, molecular, or clinical characteristics.
Abstract:
Thyroid follicular adenomas and adenomatous thyroid nodules are a frequent finding in geographical areas with iodine deficiency. They occur as hypofunctioning (scintigraphically cold) or hyperfunctioning (scintigraphically hot) nodules. Their predominant clonal origin suggests that they result from clonal expansion of a single cell, which is very likely the result of a prolonged increase in proliferation compared with non-affected surrounding cells. To test whether increased cell proliferation is detectable in cold thyroid nodules, we studied paraffin-embedded tissue from 40 cold thyroid nodules and their surrounding normal thyroid tissue for the occurrence of the proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1 antibody) epitopes as markers for cell proliferation. All 40 thyroid nodules were histologically well characterized and have been studied for molecular characteristics before. The labeling index (number of labeled cells versus total cell number) for nodular and surrounding tissue was calculated. In 33 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for PCNA was detectable. In 19 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for Ki-67 was detectable. Moreover, surrounding tissues with lymphocyte infiltration showed a significantly higher labeling index for both PCNA and Ki-67 compared with normal surrounding tissue. These findings are first evidence that an increased thyroid epithelial cell proliferation is a uniform feature common to most cold nodules. However, the increase of proliferation markers shows a heterogeneity that is not correlated with histopathologic, molecular, or clinical characteristics.
