Chromosomal Aberrations by Comparative Genomic Hybridization in Hürthle Cell Thyroid Carcinomas Are Associated with Tumor Recurrence

Abstract

Hürthle cell thyroid neoplasms are classified as variants of follicular neoplasms, but they have distinct clinicopathological features. Chromosomal aberrations by comparative genomic hybridization (CGH) are common in Hürthle cell neoplasms. However, there is currently only limited information concerning the relationship between the chromosomal aberrations by CGH and tumor behavior. We, therefore, investigated chromosomal aberrations in primary Hürthle cell neoplasms (13 carcinomas and 15 adenomas) using CGH and correlated the aberrations identified with tumor node metastasis (TNM) stage, tumor differentiation, capsular invasion, and tumor recurrence. Chromosomal aberrations were found in 62% (8 of 13) of carcinomas and 60% (9 of 15) of adenomas. Overall, common chromosomal gains were found on 5p (29%), 5q (36%), 7 (29%), 12p (14%), 12q (21%), 17p (29%), 17q (32%), 19p (32%), 19q (25%), 20p (21%), 20q (29%), and 22q (18%). Common chromosomal losses were found on 2q (18%) and 9q (18%). Thirty-eight percent (5 of 13) of carcinomas were TNM stage III, 31% (4 of 13) were moderately to poorly differentiated, and 46% (6 of 13) were intermediately to widely invasive. Recurrence occurred in 38% (5 of 13). Carcinomas that subsequently recurred had a greater number of chromosomal gains (9.0 vs. 1.3; <0.005) and had more frequent chromosomal gains on 12q, 19q, and 20p (<0.001), 5p, 7, 19p, and 20q (<0.005), and 12p (<0.01) than those that did not recur. Five of the eight (63%) patients with aberrations developed recurrence, whereas none of the five patients without aberrations developed recurrence. In conclusion, chromosomal gains by CGH on 5p, 7, 12p, 12q, 19p, 19q, 20p, and 20q in Hürthle cell carcinomas are associated with tumor recurrence. Such chromosomal aberrations may be predictive for recurrent disease in patients with Hürthle cell thyroid carcinoma.

Association between p53-binding protein 1 expression and genomic instability in oncocytic follicular adenoma of the thyroid

“…Amplification of chromosome 1p36 in oncocytic FA was additionally confirmed by FISH. This is consistent with the report by Wada et al, who also found a gain of chromosome 1p36 in oncocytic FA by CGH analysis [32]. In the current study, we further demonstrated a significant positive correlation between the percentage of tumor cells in FA expressing unstable 53BP1 expression and the percentage of cells positive for the expression of TP73, which is encoded by a gene located on chromosome 1p36.2-3.…”

“…This study also revealed a higher incidence of CNA in the tumor DNA of oncocytic FA exhibiting unstable 53BP1 expression, providing further evidence for a role of genomic instability during oncocytic FA tumorigenesis and its association with the pattern of 53BP1 expression. Previous CGH analyses found that chromosomal aberrations were common in oncocytic FA/Hürthle cell adenoma [30][31][32]. Although some studies have found that carcinomas have more chromosomal gains and losses than adenomas, in others the differences were not statistically significant [30][31][32].…”

“…Previous CGH analyses found that chromosomal aberrations were common in oncocytic FA/Hürthle cell adenoma [30][31][32]. Although some studies have found that carcinomas have more chromosomal gains and losses than adenomas, in others the differences were not statistically significant [30][31][32]. In contrast, Dittori et al demonstrated that the diffuse accumulation of mitochondria in thyroid follicular lesions with oncocytic features was specifically associated with aneuploidy, indicating numerical chromosomal changes [33], suggesting the existence of an association between genomic instability and oncocytic morphology regardless of histological type such as hyperplastic nodule, adenoma, or carcinoma.…”

Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases

“…Our analyses revealed similar allelic proportions in the primary tumor and the LN metastases, but highlighted the presence of LOH of the entire chromosome 19 in the PLM. Interestingly, results from several comparative genomic hybridization (CGH) studies have indicated that a gain of chromosome 19 is positively associated with thyroid tumor aggressivity and recurrence, including lung metastases (Tallini et al 1999, Wada et al 2002. …”

Overexpression of the S-phase kinase-associated protein 2 in thyroid cancer

“…Therefore, although there are different reports of overexpression of Skp2 protein in human haematological and solid cancers (Gstaiger et al 2001, Kudo et al 2001, Latres et al 2001, Chiarle et al 2002, Masuda et al 2002, Signoretti et al 2002, Li et al 2004, so far there are no studies regarding the clinical significance or the biological behaviour of Skp2 expression in human thyroid carcinomas. Most interestingly, genetic alterations that result in gain of part or of the entire short arm of chromosome 5, where the Skp2 gene has been assigned at 5p13, frequently occur in PTC, Hurthle carcinomas and ATC (Hemmer et al 1999,Wada et al 2002, Foukakis et al 2005, suggesting that Skp2 may be the target of gene amplification in a fraction of thyroid cancer.…”