Tall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers.
Expression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry.
Expression of the PROM1 gene, encoding the cancer stem cell marker CD133, was elevated in tall cell variant compared to classic papillary thyroid carcinoma in a large cohort of unmatched samples from The Cancer Genome Atlas Thyroid Cancer database (P < .001). By immunohistochemistry in age and stage matched samples, CD133 protein was confirmed to be significantly increased in tall cell variant versus classic papillary thyroid carcinoma (P = .006). Analyzing all thyroid cancers, high PROM1 expression was associated with worse disease-specific survival. Optimal cutoffs were determined to define a tall cell variant-like cancer stem cell signature characterized by high PROM1, high ALDH1A3, and low CD24 expression. Classic papillary thyroid carcinoma with a tall cell variant-like gene signature had worse recurrence disease-free survival compared to classic papillary thyroid carcinoma with a non-tall cell variant signature (P = .02).
Tall cell variant of papillary thyroid carcinoma has increased expression of cancer stem cell markers compared to classic papillary thyroid carcinoma. The tall cell variant-like cancer stem cell gene signature identified a molecular subtype of classic papillary thyroid carcinoma that has a worse recurrence-free survival.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Surgery
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- A comparison of the clinicopathological features and prognoses of the classical and the tall cell variant of papillary thyroid cancer: a meta-analysis.Oncotarget. 2017; 8: 6222-6232
- Aggressive variants of papillary thyroid microcarcinoma are associated with extrathyroidal spread and lymph-node metastases: a population-level analysis.Thyroid. 2013; 23: 1305-1311
- Classical and follicular variant of papillary thyroid carcinoma: a comparative study on clinicopathologic features and long-term outcome.World J Surg. 2006; 30: 752-758
- Follicular variant of papillary thyroid carcinoma is a unique clinical entity: a population-based study of 10,740 cases.Thyroid. 2013; 23: 1263-1268
- c-Met expression in tall cell variant papillary carcinoma of the thyroid.Cancer. 2003; 98: 1386-1393
- Tall cell variant of papillary thyroid carcinoma: impact of change in WHO definition and molecular analysis.Endocr Pathol. 2019; 30: 43-48
- The cancer stem cell: premises, promises and challenges.Nat Med. 2011; 17: 313-319
- In vitro identification and characterization of CD133(pos) cancer stem-like cells in anaplastic thyroid carcinoma cell lines.PLoS One. 2008; 3: e3544
- CD133+ anaplastic thyroid cancer cells initiate tumors in immunodeficient mice and are regulated by thyrotropin.PLoS One. 2009; 4: e5395
- Cancer stem cells as a potential therapeutic target in thyroid carcinoma.Oncol Lett. 2016; 12: 2254-22560
- Cancer stem cells in the thyroid.Front Endocrinol (Lausanne). 2016; 7: 20
- Insulin receptor isoforms and insulin-like growth factor receptor in human follicular cell precursors from papillary thyroid cancer and normal thyroid.J Clin Endocrinol Metab. 2011; 96: 766-774
- Tumorigenic and metastatic activity of human thyroid cancer stem cells.Cancer Res. 2010; 70: 8874-8885
- CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy.Eur J Nucl Med Mol Imaging. 2013; 40: 61-71
- Integrated genomic characterization of papillary thyroid carcinoma.Cell. 2014; 159: 676-690
- Visualizing and interpreting cancer genomics data via the Xena platform.Nat Biotechnol. 2020; 38: 675-678
- Rationales for the use of cancer stem cells markers in the staging of papillary thyroid carcinoma.J Oncol. 2019; 20191659654
- Association of cancer stem cell markers with aggressive tumor features in papillary thyroid carcinoma.Cancer Control. 2015; 22: 508-514
- Immunohistochemical analysis of cancer stem cell marker expression in papillary thyroid cancer.Front Endocrinol (Lausanne). 2019; 10: 523
- Prognostic value of putative cancer stem cell markers (CD24, CD44, CD133, and ALDH1) in human papillary thyroid carcinoma.Pathol Res Pract. 2017; 213: 956-963
- Expression of cancer stem cell markers is more frequent in anaplastic thyroid carcinoma compared to papillary thyroid carcinoma and is related to adverse clinical outcome.J Clin Pathol. 2014; 67: 125-133
- All-trans retinoic acid suppresses malignant characteristics of CD133-positive thyroid cancer stem cells and induces apoptosis.PLoS One. 2017; 12e0182835
- Coexpression of EpCAM, CD44 variant isoforms and claudin-7 in anaplastic thyroid carcinoma.PLoS One. 2014; 9: e94487
- Molecular profiles of cancer stem-like cell populations in aggressive thyroid cancers.Endocrine. 2016; 53: 145-156
- Overexpression of p53 in tall cell variants of papillary thyroid carcinoma.Surgery. 1996; 120: 1046-1050
- AP-2alpha expression in papillary thyroid carcinoma predicts tumor progression and poor prognosis.Cancer Manag Res. 2018; 10: 2615-2625
- Targeting the SUMO pathway as a novel treatment for anaplastic thyroid cancer.Oncotarget. 2017; 8 (114801–11415)
Published online: August 03, 2021
Accepted: March 23, 2021
© 2021 Elsevier Inc. All rights reserved.