Kalliopi Pazaitou-Panayiotou

Adiponectin: a link between obesity and cancer

Adiponectin, an insulin-sensitising hormone produced by adipocytes, has direct antidiabetic, antiatherogenic, anti-inflammatory and antiangiogenic properties. Circulating adiponectin levels are lower in obesity, a disease state that is associated with certain malignancies. Recently, accumulating evidence suggests that adiponectin may have an important protective role in carcinogenesis. There is also evidence that at least some, if not most, cancer cell types express adiponectin receptors; thus adiponectin may act on tumour cells directly by binding and activating adiponectin receptors and downstream signalling pathways. Through its antiangiogenic properties, and also possibly through other mechanisms regulating cell proliferation discussed in this review, adiponectin may prove to be an effective novel anticancer agent. Large association and prospective studies to assess adiponectin levels in relation to risk from cancer, as well as mechanistic studies to prove adiponectin’s role in the development of malignancies, and interventional trials to address potential roles of adiponectin in cancer pathogenesis and therapeutics are needed.

Circulating adiponectin is inversely associated with risk of thyroid cancer: in vivo and in vitro studies.

CONTEXT Circulating adiponectin has been inversely associated with risk for several malignancies. Its association with thyroid cancer has not yet been evaluated. OBJECTIVE/METHODS We measured circulating adiponectin levels in 175 thyroid carcinoma patients and 107 controls. We also examined the expression of adiponectin receptors (AdipoR1 and AdipoR2) using immunohistochemistry in 82 thyroid carcinoma tissues and using RT-qPCR in 40 human thyroid carcinoma tissues (32 papillary, six follicular/Hurthle, one anaplastic, one medullary), four normal human thyroid tissue specimens, and the BHP7 and SW579 thyroid cancer cell lines. We then utilized these thyroid cancer cell lines to investigate whether adiponectin could directly regulate cell cycle or apoptosis. RESULTS Thyroid cancer patients had lower circulating adiponectin levels than controls (17.00 ± 6.32 vs. 19.26 ± 6.28 μg/ml; P < 0.001). Subjects in the highest tertile of circulating adiponectin concentrations had significantly lower odds of developing any type of thyroid carcinoma (odds ratio = 0.29; 95% confidence interval, 0.16-0.55), or papillary thyroid carcinoma (odds ratio = 0.27; 95% confidence interval, 0.14-0.55), before and after adjustment for potential confounders. Both thyroid carcinoma cell lines and tissues expressed AdipoR1 and AdipoR2. Recombinant adiponectin did not exert a clinically significant direct effect on cell cycle, proliferation, or apoptosis in thyroid cancer cell lines in vitro. CONCLUSIONS Circulating adiponectin is independently and inversely associated with the risk of thyroid cancer. Human thyroid carcinomas and cell lines express adiponectin receptors. However, in the absence of a major direct effect of adiponectin on thyroid cancer cell lines in vitro, the negative association observed herein may be attributed to the metabolic effects of adiponectin.

Obesity and thyroid cancer: epidemiologic associations and underlying mechanisms

The incidence of thyroid cancer has been rising over the past few decades along with a parallel increase in obesity.

Telomere Length in Neoplastic and Nonneoplastic Tissues of Patients with Familial and Sporadic Papillary Thyroid Cancer

INTRODUCTION Many studies have found an association between altered telomere length (TL), both attrition or elongation, and cancer phenotype. Recently, we have reported that patients with the familial form of papillary thyroid cancer (FPTC) have short telomeres in blood leucocytes. AIM To evaluate relative TL (RTL) at somatic level in neoplastic and nonneoplastic tissues of patients with FPTC (n = 30) and sporadic PTC (n = 46). METHODS RTL was measured by quantitative PCR in neoplastic thyroid tissues, in the corresponding nontumor thyroid tissues (normal contralateral thyroid), and in other extrathyroidal tissues (lymph nodes, muscles, or buccal mucosa). RTL was also measured in adenomas and hyperplastic nodules. In a subset of samples, telomerase expression was measured by quantitative PCR. RESULTS Mean ± SD RTL of FPTC patients was short in neoplastic thyroid tissues (0.87 ± 0.2) with no difference from the normal contralateral thyroid tissues (0.85 ± 0.11) and extrathyroidal tissues (0.85 ± 0.31). On the contrary, in patients with sporadic PTC, the mean ± SD RTL in the neoplastic tissues (1.73 ± 0.63) was significantly shorter than that found in normal contralateral tissues (2.58 ± 0.89) and extrathyroidal tissues (2.5 ± 0.86). For all tissue samples (cancer, normal thyroid, and nonthyroidal tissues) the mean ± SD RTL of familial cases was shorter (P < 0.0001) than that found in tissues from sporadic PTC. RTL of FPTC was also lower (P < 0.0001) than that of 23 follicular adenomas (1.6 ± 0.7) and 24 hyperplastic nodules (2.2 ± 0.9). CONCLUSIONS Our results demonstrate that short telomeres are a consistent feature of PTC, which in familial cases, is not restricted to the tumor tissue. This finding suggests that FPTC has a distinct, heritable, genetic background.

The corticotropin releasing factor system in cancer: expression and pathophysiological implications

Malignant tumors express multiple factors that have some role in the regulating networks supporting their ectopic growth. Recently, increased interest has been developing in the expression and biological role of the neuropeptides and receptors of the corticotropin releasing factor (CRF) system, the principal neuroendocrine mediator of the stress response, especially in the light of several R&D programs for small molecule antagonists that could present some anticancer therapeutic benefit. In the present article, we review the literature suggesting that the CRF system could be involved in the regulation of human cancer development. Potential implication in growth, metastasis, angiogenesis, or immune parameters via activation of locally expressed receptors could be clinically exploited by presenting targets of new therapeutic approaches.

Pituitary Metastasis of Follicular Thyroid Carcinoma

Objective: The case of a 60-year-old male patient with follicular thyroid cancer who developed a pituitary mass proved to be a metastasis from thyroid cancer. Methods: Assessment with whole-body scan, ultrasound, computed tomography and thyroglobulin measurements. Results: Despite surgery and repeated doses of radioiodine, the patient developed diplopia and ptosis of the right eyelid, along with increasing thyroglobulin levels. A pituitary mass was discovered, with no signs of pituitary deficiency. The mass was removed and found to consist of neoplastic cells immunohistochemically positive to thyroglobulin. Conclusions: Distant metastases may develop in cases of follicular thyroid carcinoma, even after repeated doses of 131I. Metastatic follicular thyroid carcinoma to the pituitary is a rare entity.

Ectopic Cushing's syndrome due to CRH secreting liver metastasis in a patient with medullary thyroid carcinoma.

Ectopic production of CRH by a medullary thyroid carcinoma or its metastases is a rare cause of ectopic Cushing’s syndrome (ECS). We report a 45-year old male with medullary thyroid carcinoma (MTC), who, 24 years following the initial diagnosis, presented with clinical and biochemical evidence of an ACTH dependent Cushing’s syndrome. Rapid deterioration of his clinical condition and elevated cortisol levels were observed. Computed tomographic imaging of the abdomen revealed extensive liver metastases. The patient underwent fine needle aspiration biopsy of a liver lesion and immunohistochemistry showed that the cells expressed calcitonin, carcino-embryonic antigen and synaptophysin. Further analysis revealed that the material also expressed CRH. This is an unusual case of a CRH-secreting liver metastasis from a medullary thyroid carcinoma 24 years after the initial diagnosis of MTC.

Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer

OBJECTIVE Several components of the GH and IGF systems have been implicated in the development of malignancies. All components of these hormonal systems have never been jointly evaluated in female breast cancer, and previous studies have not examined the role of IGF-binding proteins (IGFBP-4, IGFBP-6) or GH-binding protein (GHBP). DESIGN Hospital-based case-control study. METHODS In this sample of primarily postmenopausal women, we obtained serum measures of IGF-I, IGF-II, and binding proteins IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, as well as GHBP, insulin, and leptin from 74 breast cancer cases and 76 control subjects. RESULTS In crude analyses, we found lower age-standardized mean IGF-I, IGFBP-3, IGFBP-4, IGFBP-6, and higher IGFBP-1 and GHBP in breast cancer cases when compared with controls. Multivariate models mutually adjusted for other GH-IGF system components and classical breast cancer risk factors demonstrated an inverse association between IGFBP-3 and risk of breast cancer (odds ratio (OR) = 0.2, P < 0.01) and a direct association between GHBP and disease risk (OR = 3.3, P < 0.01). No significant associations were detected in multivariate analyses among IGF-I, IGF-II or IGFBP-1, IGFBP-4, IGFBP-6 with risk of breast cancer, indicating that these factors may not have effects independent of and/or comparable with IGFBP-3 and GHBP. CONCLUSIONS These results support a protective role of IGFBP-3 and demonstrate for the first time an increased risk of breast cancer with higher GHBP, after accounting for variation in IGFs, IGFBPs, and classical breast cancer risk factors.

The Immunocytochemistry Is a Valuable Tool in the Diagnosis of Papillary Thyroid Cancer in FNA's Using Liquid-Based Cytology

Introduction. Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid. An accurate cytological diagnosis is based on distinctive cytological features in combination with immunocytochemistry. Methods. A number of 83 fine needle aspirations, positive for papillary thyroid cancer (44 from thyroid nodules and 39 from cervical lymph nodes), were studied using Thin Layer Cytology. A panel of the immunomarkers Cytokeratin-19, Galectin-3, HBME1, CD-44, CD-56, and E-Cadherin was performed. Results. Positive expression of CK-19 was observed in 77 cases (92.7%), of Galectin-3 in 74 cases (89.1%), of HBME1 in 65 (78.3%), and of CD-44 in 72 cases (86.7%). Loss of expression of CD-56 was observed in 80 cases (96.4%) and of E-cadherin in 78 (93.9%). Conclusions. Our data suggest that Thin Layer Cytology increases the diagnostic accuracy in papillary carcinoma and seems to be a promising technique for further investigation of thyroid lesions permitting the possibility to use archive material. Positive immunoexpression of CK-19, Galectin-3, HBME-1, and CD-44 improves the diagnostic accuracy of papillary thyroid cancer. Furthermore, loss of E-cadherin and of CD-56 expression is a feature of malignancy.

Thyroglossal duct cyst carcinomas: is there a need for thyroidectomy?

OBJECTIVE: Thyroglossal duct cyst (TGDC) carcinoma is a rare entity and its management is controversial. The aim of this retrospective study was to: (a) identify patients with TGDC carcinoma followed up in our clinic and (b) study specific characteristics of the disease and their association with thyroid carcinoma. DESIGN: Medical files of patients with TGDC carcinoma were reviewed and tumour characteristics, lymph node metastases, treatment and follow-up were evaluated. RESULTS: A total of 6 patients, 4 females and 2 males, mean age 39.3 years (median 33.5), were treated for papillary thyroid carcinoma arising in a TGDC carcinoma of the thyroid gland was found simultaneously in 4 of these patients, while in one patient thyroid carcinoma developed 10 years after the diagnosis of TGDC carcinoma. A variable clinical picture and presentation was recorded. The most aggressive manifestation of the disease in terms of local infiltration, local recurrence and lymph node metastases was observed in our youngest patients. CONCLUSIONS: Long-term follow-up is necessary for patients with thyroid carcinoma arising in a TGDC. In view of the frequent co-existence of thyroid cancer in these patients, we would recommend detailed thyroid evaluation and, eventually, total thyroidectomy at initial diagnosis of TGDC carcinoma.