Tumor Suppressor Gene Allelic Loss Profiles of the Variants of Papillary Thyroid Carcinoma

Abstract

Papillary thyroid carcinoma (PTCa) is a relatively common, indolent tumor that usually has an excellent prognosis. While the diagnosis of conventional PTCa is relatively straightforward, encapsulated tumors with follicular growth pattern and unusual or incomplete cytologic features of papillary carcinoma can be diagnostically challenging. Encapsulated, noninvasive tumors are particularly controversial as the differential diagnosis includes a nonneoplastic nodule, a benign follicular adenoma, and papillary carcinoma. In this study, we performed molecular genotyping to identify loss of heterozygosity of tumor suppressor genes in conventional PTCa and in several different morphologic variants, including follicular variant, tall cell variant, and oncocytic variant. Our data demonstrate that conventional PTCas have the lowest frequency of allelic loss (7%), as compared with follicular, oncocytic, and tall cell variants (19%, 34%, and 20%, respectively). Frequency of allelic loss increased with increasing size of the tumors, but did not correlate with age, gender, extrathyroidal extension, or lymph node metastases. Though it is unlikely that these results will enable the distinction between different variants of papillary carcinoma, the finding of significant rates ofallelic loss in the variants of PTCa provides additional evidence of malignancy and may be useful in distinguishing encapsulated tumors from nonneoplastic or benign nodules.

Liver transplantation for hepatocellular carcinoma: Extension of indications based on molecular markers

“…The 18 MS analyzed in this report have been previously tested in a number of cancer types including lung [16], ovarian [17], bone [18], thyroid [20], pancreatobiliary [21], brain [22], and melanoma [23] was largely based on empiric observation of an association between AI at these loci and cancer. The 9 MS for which AI correlated with HCC recurrence comprise the panel used to calculate FAI; attempts to reduce the number of MS used to calculate FAI while preserving its predictive ability were unsuccessful due to the high incidence of noninformative MS. One of the 9 significant MS, MYCL 5NT, is located within the known oncogene l-myc on chromosome 1p34, and among all the MS tested this one had the strongest correlation with HCC recurrence (p < 0.0001).…”

“…Manual microdissection was employed in preference to the more cumbersome laser-capture technology based on side-by-side comparison in our laboratory that failed to demonstrate any advantage to LCM in this setting. In addition to analysis of HCC [12,14,15], the techniques employed in the current work have been previously validated in a variety of other tumors including lung [16], ovary [17], bone [18], hemangioblastoma [19], thyroid [20], pancreas [21], meningioma [22], melanoma [23], neuroendocrine [24], and esophagus [25].…”

Clinical Features and Outcome of the Tall Cell Variant of Papillary Thyroid Carcinoma

“…The genetic mechanism behind the aggressive behavior of TCV is not fully understood. It has been found in one study that TCV is associated with a higher percentage of loss of heterozygosity of tumor suppressor genes (20%) compared with conventional PTC (7%) 12 . In another study, RET/PTC3 rearrangement, which leads to activation of downstream mitogenic signaling pathways, was found in 35.8% of TCV 13 .…”

Thyroidectomies from patients with history of therapeutic radiation during childhood and adolescence have a unique mutational profile

“…Papillary thyroid carcinomas have a relative low rate of tumor suppressor gene mutations, as measured by LOH to detect allele deletion. 29 Follicular derived carcinomas, in contrast, have a much higher rate of tumor suppressor gene loss. 30 Follicular adenomas have low rates, and hyperplastic and non-neoplastic thyroid tissues have negligible rates of tumor suppressor gene loss.…”