Search

Background:Prohibitin (PHB) is a multifunctional protein that is localized in different intracellular sites. PHB may exert different roles in tumorigenesis, having either a permissive action on tumor growth or an oncosuppressor role, depending on the cellular context. The objective of this study was to evaluate PHB expression in normal thyroid tissues, thyroid follicular adenomas (FAs), and papillary thyroid carcinomas (PTCs).Methods:PHB expression was analyzed by immunohistochemistry, Western blot, and quantitative reverse transcription polymerase chain reaction (RT-PCR). Transfections in the BCPAP and TPC-1 thyroid cancer cell lines were used to evaluate the PHB promoter activity.Results:In terms of protein and mRNA levels, normal tissues from patients with serum thyrotropin (TSH) values >0.8 mU/L had PHB levels that were significantly reduced compared to specimens from patients with serum TSH values <0.5 mU/L, suggesting that TSH exerts an inhibitory effect on PHB expression. Consistent with this was the finding that the presence of TSH was associated with low PHB levels in normal FRTL5 thyroid cells. Immunohistochemical analysis showed relatively low and high PHB expression in FAs and PTCs, respectively. PHB mRNA and protein overexpression, as assessed by quantitative RT-PCR and Western blot, was noted only in PTCs bearing the BRAFV600Emutation. Notably, cell transfection experiments suggested that presence of the BRAFV600Emutation may be associated to increase of the PHB promoter activity.Conclusions:PHB is overexpressed in PTCs bearing the BRAFV600Emutation. We postulate that the presence of the BRAFV600Emutation increases PHB promoter activity and therefore potentially mediates effects of this mutation on the behavior of BRAFV600Epositive PTCs. [ABSTRACT FROM AUTHOR]

Background:Serum thyroglobulin (Tg) stimulation by recombinant human TSH (rhTSH), in combination with neck ultrasonography (US), is an important tool in the first follow-up of differentiated epithelial cell thyroid carcinoma (DTC) patients. The objective of this study was to investigate if a second rhTSH stimulation, performed 2–3 years later, is of clinical utility in the follow-up of these patients.Methods:One hundred and one consecutive ambulatory DTC patients were studied. The great majority of them (89/101) were low-risk patients, being stage I or II at tumor node metastasis (TNM) staging classification. All study patients had been treated by surgery and radioiodine ablation, and exhibited, at first rhTSH follow-up, either undetectable Tg (≤1 ng/mL) (rhTSH1-Tg−, n 89 patients considered as free of disease) or low Tg (>1–5 ng/mL) (rhTSH1-Tg, n 12 patients considered with uncertain prognosis), with no US evidence of residual disease. In all patients, serum Tg measurement after a second rhTSH stimulation and neck US were performed.Results:At the second follow-up, all 89 rhTSH1-Tg−patients showed a negative US, and Tg became low positive only in one case, whereas it remained undetectable in the other patients. The overall negative predictive value of rhTSH1-Tg− was, then, 98.9. Out of the remaining 12 patients (i.e., rhTSH1-Tg patients), 2 showed disease persistence/recurrence (with a positive predictive value of rhTSH1-Tg of 16.7) and 6 became Tg−.Conclusions:A second rhTSH stimulation is useless in DTC patients who were rhTSH-Tg and imaging negative at first follow-up, while it is suggested in patients with detectable, although low, rhTSH-Tg levels at first follow-up: in the absence of clinical or US evidence of disease persistence, these patients should not be retreated by radioiodine, but simply scheduled for a later rhTSH stimulation. [ABSTRACT FROM AUTHOR]

Background:Hepatocyte nuclear factor (HNF)-1α and HNF-1β are related transcription factors that are mainly expressed in liver cells. Our previous study showed that HNF-1β was highly expressed in papillary thyroid cancer cell lines and tumors. HNF-1α mRNA, however, was not detected in differentiated thyroid cancer cell lines. The objective of this study was to determine whether HNF-1α is expressed in dedifferentiated anaplastic thyroid cancer cells.Methods:Total RNA isolated from six anaplastic thyroid cancer cell lines and 38 surgical samples was analyzed for HNF-1α mRNA by conventional reverse-transcription polymerase chain reaction (RT-PCR) or real-time RT-PCR. HNF-1α DNA binding activity was measured by gel retardation assay and HNF-1α protein was identified by Western blotting.Results:HNF-1α mRNA was expressed in four of the six anaplastic cell lines. The presence of HNF-1α protein and DNA binding activity was detected in three lines with higher HNF-1α mRNA level. Three cell lines also expressed HNF-1β. HNF-1α transcripts were also detected in five out of six anaplastic tumors, but not in the papillary tumors except one with weak PCR signal.Conclusion:HNF-1α mRNA was detected in high frequency in anaplastic thyroid cancer cell lines and tumors. HNF-1α might play a role in the pathogenesis of anaplastic thyroid cancer. [ABSTRACT FROM AUTHOR]

Immunohistochemistry provides insights in the expression of functional proteins and of their localization in normal thyroid tissue and in thyroid diseases. In hyperfunctional thyroid tissues, staining for sodium/iodide symporter (NIS), pendrin, thyroid peroxidase (TPO), and thyroglobulin (Tg) is increased. In hypofunctioning thyroid tissues, NIS staining is markedly decreased; in benign hypofunctioning adenomas, the expression of the other functional proteins is unmodified or slightly decreased, whereas their expression is profoundly decreased or absent in differentiated thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Background:Thyrogobulin (Tg) assay of material from fine-needle aspiration of neck masses can help distinguish neck masses of thyroid origin from other masses. We describe its utility in a patient with an unusual constellation of findings, a neck lump identified as a lymph node metastasis from a contralateral occult papillary thyroid carcinoma (PTC).Summary:A 56-year-old woman was referred to our center for evaluation of a 15-mm right lateral cervical neck mass which was strongly hypoechoic, not homogenous and contained several microcalcifications. There was no family history of thyroid disease, the patient was euthyroid and was not taking medications for thyroid disorders. On physical examination the thyroid was slightly enlarged and was normal on ultrasound except for a 1 × 3 mm hypoechoic nodule in the middle of the left lobe. Ultrasound-guided fine-needle aspiration biopsy (FNAB) of the right lateral cervical mass was performed with the Tg concentration of the FNAB washout liquid being >300 ng/mL and the cytology showing lymphoid elements mixed with polymorphous epithelial cells with atypical nuclei, suggesting lymph node metastasis from a cancer of epithelial origin. A lymph node metastasis from a papillary thyroid microcarcinoma (micro-PTC) was the presumptive diagnosis with the preoperative staging being Tx N1b. The patient underwent total thyroidectomy and bilateral lymph node dissection. At pathology, the right cervical mass was confirmed as lymph node metastasis of a PTC, and a unifocal micro-PTC was found in the middle left lobe. The patient was readmitted for a therapeutic 131I dose (4810 MBq). At the time of 131I administration, the whole-body scan showed only minimal thyroid bed uptake and serum Tg was <1 ng/mL. She was maintained on l-thyroxine treatment (150 μg/d). Five year later she did not have evidence of recurrent or residual PTC.Conclusions:We describe the first case of contralateral lymph node metastasis from a unifocal micro-PTC identified by the detection of high Tg levels in the wash-out liquid of FNAB. [ABSTRACT FROM AUTHOR]

Context: Radioiodine uptake is rarely observed in normal non-lactating breast tissue. Investigation of the in vivoregulation of iodide uptake in breast tissue may be useful for the induction of radioiodine uptake in breast cancer tissue for diagnostic and therapeutic purposes. Case reports: We report the cases of two post-menopausal women who underwent radioiodine therapy for papillary thyroid carcinoma and in whom breast uptake of radioiodine on post-therapy whole body scan (WBS) was observed. Methods and results: In both patients, elevated serum prolactin levels (123 ng/mL in patient 1 and 48 ng/mL in patient 2) were documented at the time when radioiodine uptake in the breast was observed. The hyperprolactinemia was due to prolonged treatment with the anti-dopaminergic neuroleptic risperidone in Case 1, and chronic renal failure in Case 2. When prolactin levels were normalized (by withdrawal of risperidone in Case 1 and with cabergoline in Case 2), breast tissue uptake was no longer evident on WBS. Conclusion: These cases provide the first documented correlation between serum levels of endogenous prolactin and radioiodine uptake by involuted breast tissue in humans. [ABSTRACT FROM AUTHOR]