Sporadic Papillary Carcinoma Research Articles

FAMILIAL NON-MEDULLARY THYROID CARCINOMA.

Familial non-medullary thyroid carcinoma (FNMTC) is defined as cancer developing in two or more first-degree relatives if predisposing factors, for example, radiation, are absent. The disease can be either syndromic, when it is a component of complex genetic syndromes, or non-syndromic (95% cases). The genetic basis of non-syndromic FNMTC is unknown; the clinical behavior of tumorsis unclear and, at times, contradictory. To analyze clinical manifestations of FNMTC and compare them with the data for sporadic papillary thyroid carcinomas in patients of the same age groups. We examined 22 patients (a "parents" group and a "children" group) suffering from the non-syndromic FNMTC. For comparison, two groups of sporadic papillary carcinomas patients of the same age were drawn up("adult" and "young"). We analyzed tumor size and frequency of the distributionby the categoryof TNM system, invasiveness, multifocality, metastases to lymph nodes, type and extent of surgical and radioiodine treatment, and prognosis according to the MACIS criterion. Whether sporadic or familial, the tumor size, metastatic potential, and invasive potential are higher in young people, asalready known. There was no significant difference between the "parents" and "adult" groups of patients in terms of tumor parameters. One exception was the higher frequency of multifocal tumors in the FNMTC patients. Meanwhile, compared to the "young" sporadic papillary carcinomas patients, the FNMTC "children" had a higher frequency of T2 tumors, metastasizing (N1a-N1ab), and multifocal tumors, but a lower frequency of carcinomas with intrathyroidal invasions.In the FNMTC "children" compared to FNMTC "parents" was a higher frequency of T2 tumors, metastasizing carcinomas, and tumors with capsular invasion. FNMTC carcinomas are more aggressive than sporadic ones, especially in patients who are first-degree relatives in a family with parents already diagnosed with the disease.

Familial Papillary Thyroid Carcinoma (FPTC): a Retrospective Analysis in a Sample of the Bulgarian Population for a 10-Year Period.

In recent years, there are numerous reports indicating the presence of familial papillary carcinoma. Unfortunately, no genetic defect can be linked directly to the disease. In this study, we set the goal to make a retrospective analysis of the cases with papillary carcinoma in the Department of Endocrine Surgery for the past 10years, to compare the characteristics of sporadic and familial forms of the disease and to find families with hereditary papillary carcinoma. The study included 810 patients treated for thyroid cancer in the Department of Endocrine Surgery, USBALE "Acad. Iv. Penchev" Hospital, between January 1, 2006 and December 31, 2015. We used chi square test to determine statistical significant difference. The data analysis and interpretation was performed on SPSS 20.0. Both groups had similar demographic distribution. We found that 587 patients have sporadic papillary carcinoma, while 147 have a relative with thyroid pathology in the first degree of kinship. In 8 patients, there was a blood relative with thyroid cancer. When we compared the two groups, we found statistically significant difference only in tumor size. There was no significant difference in aggressiveness of the thyroid cancer (multifocality and lymph node metastasis). When analyzing the results, we identified 147 patients with a family history of thyroid disease (20%). In 8 patients (5.44%), we found at least one relative with papillary thyroid carcinoma. However, our study does not demonstrate any difference in the aggressiveness of familial and sporadic papillary thyroid carcinoma.

Ultrasonographic Screening for Thyroid Cancer in Siblings of Patients with Apparently Sporadic Papillary Carcinoma

Ultrasonographic Screening for Thyroid Cancer in Siblings of Patients with Apparently Sporadic Papillary Carcinoma

Ultrasonographic Screening for Thyroid Cancer in Siblings of Patients with Apparently Sporadic Papillary Carcinoma

Epidemiological studies have shown a higher risk of thyroid cancer among individuals who have a relative with papillary thyroid cancer (PTC) compared to those without a family history. This study evaluated the prevalence of thyroid cancer among subjects with only one first-degree relative (sibling) with PTC who had no palpable nodules, factors predictive of this malignancy, and the characteristics of tumors discovered during ultrasonographic screening. A total of 757 siblings of 447 patients with apparently sporadic PTC were examined. Nodules were palpable in 34 subjects (excluded). The 723 individuals without palpable abnormalities were submitted to thyroid ultrasonography and comprised the study group. The control group, consisting of 241 volunteers without a family history of thyroid cancer matched for gender and age to the study group, was also submitted to thyroid ultrasonography. All nodules ≥ 5 mm were examined by fine-needle aspiration cytology. Subjects with benign cytology were not submitted to surgery, whereas the subjects having malignant, suspicious for a malignancy, indeterminate, or inadequate cytology were referred for thyroidectomy. Ultrasonography detected nodules in 303 (41.9%) study subjects. PTC was observed in 5.94% of the 723 subjects studied (8% women and 3.75% men, p=0.017) and in 14.2% of the 303 subjects with nonpalpable nodular disease. In the control group, 80 (33.2%) of the volunteers had nodules. PTC was observed in 1.2% of them and in 3.8% of those with nodular disease. In addition, 7.17% of the 447 patients had siblings with PTC detected only by ultrasonography. Multicentricity of the tumor was the main predictor of the presence of malignancy in siblings of patients with PTC. Twenty-two subjects (3% of those screened) had tumors that were not intrathyroid microcarcinomas (whereas all three tumors detected in controls were intrathyroid microcarcinomas). Screening permitted an earlier diagnosis of the disease when compared to siblings with a spontaneous diagnosis. The present results favor ultrasonographic screening of first-degree relatives of patients with apparently sporadic multicentric PTC, especially among women.

Biological behavior and prognosis of familial papillary thyroid carcinoma

Although the responsible genes have not yet been identified, it is known that the risk of nonmedullary thyroid carcinoma is elevated in individuals with 1st-degree relatives with nonmedullary thyroid carcinoma. However, it remains controversial whether the biological character of familial nonmedullary carcinoma (FNMTC) differs from that of sporadic carcinoma. In this study, we investigated the prevalence of familial papillary carcinoma and its biological behavior. Between 1987 and 2004, 6,015 patients underwent initial surgical treatment for papillary carcinoma at Kuma Hospital and 273 (4.5%) were classified as having familial carcinoma. We compared the biological characteristics including prognosis between familial and sporadic papillary carcinomas. Disease-free survival and cause-specific survival rates of familial carcinoma did not differ from those of sporadic carcinoma. Familial papillary carcinoma showed multicentricity and recurrence to the thyroid more frequently than sporadic carcinoma. There were no differences in other clinicopathological parameters between the 2 groups. Prognosis of patients with familial papillary carcinoma did not differ from that of those with sporadic papillary carcinoma. Although routine total thyroidectomy is recommended for familial papillary carcinoma, its therapeutic strategy can otherwise be the same as that for sporadic papillary carcinoma.

Absence of a specific radiation signature in post-Chernobyl thyroid cancers

Thyroid cancers have been the main medical consequence of the Chernobyl accident. On the basis of their pathological features and of the fact that a large proportion of them demonstrate RET-PTC translocations, these cancers are considered as similar to classical sporadic papillary carcinomas, although molecular alterations differ between both tumours. We analysed gene expression in post-Chernobyl cancers, sporadic papillary carcinomas and compared to autonomous adenomas used as controls. Unsupervised clustering of these data did not distinguish between the cancers, but separates both cancers from adenomas. No gene signature separating sporadic from post-Chernobyl PTC (chPTC) could be found using supervised and unsupervised classification methods although such a signature is demonstrated for cancers and adenomas. Furthermore, we demonstrate that pooled RNA from sporadic and chPTC are as strongly correlated as two independent sporadic PTC pools, one from Europe, one from the US involving patients not exposed to Chernobyl radiations. This result relies on cDNA and Affymetrix microarrays. Thus, platform-specific artifacts are controlled for. Our findings suggest the absence of a radiation fingerprint in the chPTC and support the concept that post-Chernobyl cancer data, for which the cancer-causing event and its date are known, are a unique source of information to study naturally occurring papillary carcinomas.

Alterations of the <I>BRAF</I> Gene in Thyroid Tumors

BRAF belongs to the RAF family of protein kinases that are important components of the MAPK signaling pathway mediating cell growth, differentiation and survival. Activating point mutation of the BRAF gene resulting in V600E (previously designated as V599E) is a common event in thyroid papillary carcinoma, being found in approx 40% of this tumor. It has strong association with classical papillary carcinoma and tall cell and possibly Warthin-like variants. This mutation also occurs in thyroid poorly differentiated and anaplastic carcinomas, usually those containing areas of papillary carcinoma. Alterations in the BRAF gene do not overlap with RAS mutations and RET/PTC rearrangement, indicating that activation of one of the effectors of the MAPK pathway is sufficient for papillary thyroid carcinogenesis. Recently, another mechanism of BRAF activation has been identified, which involves chromosome 7q inversion that results in the AKAP9-BRAF fusion. It is rare in sporadic papillary carcinomas and is more common in tumors associated with radiation exposure. Yet another mechanism of BRAF activation may involve copy number gain, which is seen in a significant portion of thyroid follicular tumors of both conventional and oncocytic (Hürthle cell) types.

Low prevalence of BRAF mutations in radiation-induced thyroid tumors in contrast to sporadic papillary carcinomas

Point mutations of the BRAF gene have been recently described with high prevalence in papillary thyroid carcinomas. However, this molecular alteration has not been studied in radiation-induced thyroid tumors. We analyzed the prevalence of BRAF point mutations and RET/PTC rearrangements in 55 post-Chernobyl papillary carcinomas, compared with 82 sporadic papillary carcinomas. Radiation-induced tumors demonstrated a low prevalence (4%) of BRAF point mutations and high prevalence (58%) of RET/PTC rearrangements. Sporadic papillary carcinomas revealed a clearly distinct pattern, with 37% of tumors harboring BRAF mutations and 20% RET/PTC rearrangements. These results demonstrate a significant difference in the molecular genetic profile of sporadic and radiation-induced thyroid tumors.

RET oncogene activation in papillary thyroid carcinoma.

The RET proto-oncogene encodes a cell membrane tyrosine-kinase receptor protein whose ligands belong to the glial cell line-derived neurotrophic factor. RET functions as a multicompetent receptor complex that includes alphaGFRs and RET. Somatic rearrangements of RET designated as RET/PTC (from papillary thyroid carcinoma) were identified in papillary thyroid carcinoma before RET was recognized as the susceptibility gene for MEN2. There are now at least at least 15 types of RET/PTC rearrangements involving RET and 10 different genes. RET/PTC1 and RET/PTC3 are by far the most common rearrangements. All of the rearrangements are due to DNA damage and result in the fusion of the RET tyrosine-kinase (RET-TK) domain to the 5'-terminal region of heterologous genes. RET/PTC rearrangements are very common in radiation-induced tumors but have been detected in variable proportions of sporadic (i.e., non-radiation associated) papillary carcinomas. It is estimated that up to approximately half the papillary thyroid carcinomas in the United States and Canada harbor RET/PTC rearrangements, most commonly RET/PTC-1, followed by RET/PTC-3 and occasionally RET/PTC-2. The cause of these rearrangements in sporadic papillary carcinomas is not known, but the close association between their presence and the papillary carcinoma phenotype indicates that they play a causative role in tumor development. The proposed mechanisms of RET/PTC-induced tumorigenesis and the clinical and pathologic implications of RET/PTC activation are discussed.