Short Telomeres, Telomerase Reverse Transcriptase Gene Amplification, and Increased Telomerase Activity in the Blood of Familial Papillary Thyroid Cancer Patients

Capezzone, Marco; Cantara, Silvia; Marchisotta, Stefania; Filetti, Sébastiano; Santi, Maria Margherita De; Rossi, Benedetta; Ronga, Giuseppe; Durante, Cosimo; Pacini, Furio

doi:10.1210/jc.2008-0372

Cited by 84 publications

(73 citation statements)

References 38 publications

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“…In addition, we have recently demonstrated in a series of patients with familial papillary thyroid cancer (including also some patients of the present study), an imbalance of the telomeretelomerase complex at the germline level, consisting of short telomeres, increased telomerase copy number, and expression when compared with sporadic papillary thyroid cancer (Capezzone et al 2008). This alteration may contribute (among other as yet unknown abnormalities) to confer genetic predisposition to develop FNMTC and might be involved in the anticipation phenomenon.…”

Section: Capezzone Et Al: Anticipation In Familial Nmtcsupporting

confidence: 63%

Familial non-medullary thyroid carcinoma displays the features of clinical anticipation suggestive of a distinct biological entity

Capezzone¹,

Marchisotta²,

Cantara³

et al. 2008

Endocrine Related Cancer

121

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Non-medullary thyroid carcinoma (NMTC) is mostly sporadic, but familial clustering is described. We aimed to compare the features of patients with sporadic and familial NMTC (FNMTC) patients and to assess whether FNMTC patients with parent-child relationship exhibit the 'anticipation' phenomenon (earlier age at disease onset and increased severity in successive generations). Among 300 NMTCs followed in the Section of Endocrinology (University of Siena, Italy), 34 (11.3%) patients, all with the papillary histotype, (16 kindred), met the criteria of FNMTC. Twenty-seven of them (79.4%) exhibited a parent-child relationship and seven (20.6%) a sibling relationship. These patients were compared with 235 patients with sporadic papillary thyroid cancer (PTCs). To analyze the features of FNMTC of the first and second generations, we cumulated the series of Siena with 32 additional FNMTC patients (15 kindred) from the Department of Endocrinology-Endocrine Oncology, Thessaloniki, Greece. Significant difference between sporadic PTC and FNMTC patients included more frequent tumor multifocality (PZ0.001) and worse final outcome in FNMTC patients (PZ0.001). Among 47 FNMTC with parent-child relationship, we found an earlier age at disease presentation (P!0.0001), diagnosis (P!0.0001), and disease onset (PZ0.04) in the second generation when compared with the first generation. Patients in the second generation were more frequently males (PZ0.02); their tumors were more frequently multifocal (PZ0.003) and bilateral (PZ0.01), had higher rate of lymph node metastases at surgery (PZ0.02) and worse outcome (PZ0.04) when compared with the first generation. In conclusion, FNMTC displays the features of clinical 'anticipation' with the second generation acquiring the disease at an earlier age and having more advanced disease at presentation.

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Section: Capezzone Et Al: Anticipation In Familial Nmtcsupporting

confidence: 63%

Familial non-medullary thyroid carcinoma displays the features of clinical anticipation suggestive of a distinct biological entity

Capezzone¹,

Marchisotta²,

Cantara³

et al. 2008

Endocrine Related Cancer

121

View full text Add to dashboard Cite

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“…In this sense, we found an overall low percentage of aneuploid cases, and no differences in DNA ploidy status between familial (whole series and the PTC subgroups) and sporadic PTC were depicted. These findings suggest that chromosomal instability, which could result from the reported telomere length shortening (29,30), is not a common feature in these familial tumours.…”

Section: European Journal Of Endocrinologymentioning

confidence: 79%

“…Aneuploidy is a molecular feature that identifies genetic instability, and potentially, higher metastatic capacity, being commonly associated with worse disease prognosis (26,27). In two recent studies of familial PTC, although controversial (28), Capezzone et al observed shorter telomere length in the leukocytes, other non-neoplastic tissues and tumours in the familial cases when compared with patients with sporadic PTC or healthy subjects (29,30). The size reduction of these nucleoprotein complexes, which protect the ends of chromosomes from degradation and fusion, may induce chromosomal instability, and thus, aneuploidy in these familial tumours.…”

Section: Introductionmentioning

confidence: 99%

Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour

Pinto

Silva²,

Henrique

et al. 2014

European Journal of Endocrinology

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Objective: Familial non-medullary thyroid cancer has been proposed as an aggressive clinical entity. Our aim in this study is to investigate potential distinguishing features as well as the biological and clinical aggressiveness of familial vs sporadic papillary thyroid carcinoma (PTC). We assessed clinicopathological characteristics, outcome measures and DNA ploidy. Design: A matched-case comparative study. Methods: A series of patients with familial PTC (nZ107) and two subgroups, one with three or more affected elements (nZ32) and another including index cases only (nZ61), were compared with patients with sporadic PTC (nZ107), matched by age, gender, pTNM disease extension and approximate follow-up duration. Histological variant, extrathyroidal extension, vascular invasion, tumour multifocality and bilateral growth were evaluated. Ploidy pattern was analysed in available samples by DNA flow cytometry. The probabilities of disease-free survival (DFS) and overall survival (OS) were estimated according to the Kaplan-Meier (K-M) method. Results: No patient with familial PTC died of disease during follow-up (median, 72 months), contrarily to five patients (4.7%) (PZ0.06) with sporadic PTC (median, 90 months). There was a significantly higher tumour multifocality in familial PTC (index cases subgroup) vs sporadic PTC (PZ0.035), and a trend, in the familial PTC cohort with three or more affected elements, to show extrathyroidal extension (PZ0.054) more frequently. No difference was observed in DNA ploidy status. The K-M analyses showed no significant differences between both entities in relation to DFS or OS. Conclusion: Apart from multifocality, familial PTC appears to have similar clinical/prognostic behaviour when compared with sporadic forms of the disease.

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“…It is critical to explore molecular biomarkers to guide clinical decision-making with regard to the treatment of GC. TA is thought to be a critical step in the evolution of most tumor types (34)(35)(36)(37), including GC (38,39). Considerable clinical research has been conducted with the aim of assessing the correlation between TA expression and clinicopathological outcome in patients with GC, but the Size Histo T N M TNM >5 cm P/U T3/T4 positive/ positive/ TIII/IV (<5 cm) (W/M) (T1/T2) (negative) (negative) (TI/TII) Liu et al (27) 2008 English China 26 (14) --20 (6) 22 (4) 11 (15) 24 (2) Yang et al (15) 2001 English China 40 (2) 26 (14) 30 (10) 26 (14) 20 (20) -17 (23) Wu et al (17) 2006 English China 52 (12) 23 (29) 49 (3) 40 (12) 37 (15) 14 (38) 33 (19) Hu et al (23) 2004 English China 18 (17) 10 (8) 14 (4) 7 (11) 14 (4) 10 (8) -Zhan et al (31) 1999 English China 81 (13) 46 (35) 43 (38) 68 (13) 51 (30) -60 (21) Hu et al (16) 2009 English China 41 (5) 28 (13) 33 (8) 21 (20) 5 (36) 30 (11) -Wang et al (18) 2004 English China 32 (9) 19 (13) 25 (7) (21) 43 (1) 18 …”

Section: Discussionmentioning

confidence: 99%

Prognostic role of telomerase activity in gastric adenocarcinoma: A meta-analysis

Lü

Deng²,

Cao

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. Activation of telomerase is involved in carcinogenesis in most types of cancers. However, the prognostic value of telomerase activity (TA) in patients with gastric carcinoma (GC) remains controversial. We conducted a meta-analysis to assess the relationship between TA and the clinical outcome of GC. A meta-analysis of 18 studies (886 patients) was performed to evaluate the association between TA and metastasis-related parameters in GC patients by searching databases, including PubMed, MEDLINE, EMBASE, Web of Science databases, Cochrane Library and the Chinese Biomedical Literature database (CBM) (last search updated in October 2011). We used the odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association between TA and metastasis of GC. Our analysis results indicated that high telomerase activity expression tended to be associated with the presence of lymph node metastasis (866 patients) (OR=2.03, 95% CI 1.21-3.39, p=0.007), the depth of invasion (886 patients) (OR=1.87, 95% CI 1.30-2.70, p=0.0007), distant metastasis (407 patients) (OR=2.71, 95% CI 1.59-4.63, p=0.0002), tumor size (466 patients) (OR=2.14, 95% CI 1.31-3.50, p=0.002) and TNM stage (711 patients) (OR=2.39, 95% CI 1.30-4.41, p=0.005). However, high TA expression was not associated with the presence of histologic differentiation (791 patients) (OR=1.51, 95% CI 0.73-3.11, p=0.26). In conclusion, telomerase overexpression not only plays a key role in primary initiation, but also promotes invasion and metastatic progression of GC.These findings raise the possibility of using TA to screen for the prognosis of gastric cancer.

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Short Telomeres, Telomerase Reverse Transcriptase Gene Amplification, and Increased Telomerase Activity in the Blood of Familial Papillary Thyroid Cancer Patients

Abstract: Our study demonstrates that patients with FPTC display an imbalance of the telomere-telomerase complex in the peripheral blood, characterized by short telomeres, hTERT gene amplification, and expression. These features may be implicated in the inherited predisposition to develop FPTC.

Cited by 84 publications

References 38 publications

Familial non-medullary thyroid carcinoma displays the features of clinical anticipation suggestive of a distinct biological entity

Familial non-medullary thyroid carcinoma displays the features of clinical anticipation suggestive of a distinct biological entity

Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour

Prognostic role of telomerase activity in gastric adenocarcinoma: A meta-analysis

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