Renal cell carcinoma metastatic to the thyroid

Metastatic renal cell carcinoma to the thyroid is an uncommon occurrence that can cause clinical and pathologic problems in diagnosis. The authors report seven cases from the files of The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Each presented clinically as a palpable thyroid nodule months or years after the primary renal cell carcinoma had been resected. Although renal cell carcinoma is more common in men, we found a female predominance of 6:1 in this series. These lesions appear as solitary "cold" nodules on iodine 131 scans and may be misdiagnosed as primary thyroid neoplasms, especially if the renal primary is still unrecognized. A correct diagnosis is important because surgical management can be curative. The diagnosis is facilitated by the use of fat stains, electron microscopic study, and immunoperoxidase stains.     

EphB4 is overexpressed in papillary thyroid carcinoma and promotes the migration of papillary thyroid cancer cells

EphB4 tyrosine kinase receptor has been involved in various physiologic and pathologic processes, and the role of the EphB4 in tumorigenesis has recently attracted much interest. However, its function in papillary thyroid carcinoma remains poorly understood. In this study, we explored the function of EphB4 in papillary thyroid carcinoma. We found that the expression of EphB4 was significantly upregulated in clinical samples. Overexpression of EphB4 in papillary thyroid carcinoma cell lines accelerated cell migration. In contrast, downregulation of EphB4 inhibited cell migration and suppressed in vivo tumor metastasis. Furthermore, we showed that EphB4 promoted cell migration by inhibiting the phosphorylation of FAK and paxillin. Moreover, EphB4 promoted cell migration in a kinase-independent manner. Taken together, our findings suggest that EphB4 plays an important role in the progression of papillary thyroid carcinoma by stimulating cell migration and EphB4 might be a potential therapeutic target in papillary thyroid carcinoma.     

Metastatic renal cell carcinoma to the thyroid gland: a clinicopathologic study of 36 cases

BACKGROUND: Clear cell tumors of the thyroid gland in general are uncommon. Metastatic renal cell carcinoma (RCC) to the thyroid gland is a rare occurrence but must be considered in the differential diagnosis of a thyroid gland clear cell neoplasm to prevent misclassification, potentially resulting in inappropriate clinical management. METHODS: Thirty-six cases of metastatic RCC to the thyroid were retrospectively retrieved from the files of the Endocrine Registry of the Armed Forces Institute of Pathology. RESULTS: The tumors occurred in 22 women and 14 men, ages 53-80 years (mean, 64.9 years). Symptoms were present for a mean of 13.0 months. The tumors generally affected a single lobe of the thyroid gland as a solitary mass (n = 30; 83%), measuring 1.0-15.0 cm in diameter (mean, 3.8 cm). Histologically, the tumors were composed of polygonal cells with clear cytoplasm, distinct cell membranes, and small compact eccentric nuclei within a rich vascular network. Diastase-sensitive, periodic acid-Schiff-positive material (n = 22; 61%) and/or Oil Red O-positive material (n = 5; 14%) were noted. Thyroglobulin immunohistochemistry was negative in the foci of metastatic RCC. Although the majority of the patients had documented previous evidence of an RCC (n = 23; 64%) as remotely as 21.8 years before the thyroid metastases (mean, 9.4 years), the metastatic tumor to the thyroid gland was the initial manifestation of RCC in 13 patients. The majority of patients (n = 23; 64%) died with disseminated disease (mean, 4.9 years), but 13 patients (36%) were alive or had died without evidence of disease (mean, 9.1 years). CONCLUSIONS: In the presence of a clear cell tumor of the thyroid gland, the diagnostic considerations must include metastatic RCC. The light microscopic features may suggest this possibility and the diagnosis can be established by supplemental histochemical and immunohistochemical studies. Surgical treatment of the metastatic disease is suggested, as this may result in prolonged patient survival.     

Anaplastic carcinoma of the thyroid: a review of 84 cases of spindle and giant cell carcinoma of the thyroid

Eighty-four cases of spindle and giant cell carcinoma of the thyroid were reviewed. This is a swiftly growing, and rapidly fatal neoplasm that generally develops in the elderly. Treatment of this disease was generally unsuccessful with a 7.1% five-year survival rate and a mean survival period of 6.2 months from the time of tissue diagnosis. In the majority of cases, areas of well-differentiated thyroid carcinoma could be identified, supporting the concept that spindle and giant cell carcinoma results from the transformation of preexisting well-differentiated thyroid carcinoma. Because of the aggressive biologic activity of this neoplasm, we treat all cases as disseminated disease at the time of presentation. Our best therapeutic results have been obtained with a combination of surgery, irradiation, and chemotherapy; however, these results still leave much to be desired. Patients with only small foci of spindle and giant cell carcinoma, at the time of diagnosis, may have a better chance of prolonged survival.     

Extrapulmonary small cell: a novel case of small cell carcinoma of the thyroid gland

Neuroendocrine tumors comprise a large group of malignancies which share unique morphological features and are characterized by the presence of neuroendocrine markers such as synaptophysin, chromogranin-A, and CD56 (N-CAM), ranging from indolent tumors, such as carcinoid tumors, to aggressive tumors, such as small cell carcinoma. The lung is the most common site for primary neuroendocrine tumors. Extrapulmonary primary sites of small cell carcinoma are rare but have been documented arising from various sites including esophagus, stomach, colon and rectum, gallbladder, thymus, salivary gland, ovary, cervix, bladder, prostate, and skin. We present a case of small cell carcinoma arising from the thyroid gland, a site not previously described in the literature. A 59-year-old woman presented with a thyroid mass, which, after resection, showed small cell morphology and positive immunostains for TTF-1, synaptophysin, chromogranin-A, CD56, etc. Five months after diagnosis, she had widely metastatic disease. After a near-complete response to the first chemo-treatment, her disease progressed. Following local radiation and more rounds of chemotherapy, she succumbed to the disease, 15?months after diagnosis. Our patient had no pulmonary lesions at the time of diagnosis to suggest metastasis from the lung. Much like its pulmonary counterparts, this small cell carcinoma of primary thyroid origin displayed an aggressive clinical course and poor outcome. Although it shows early sensitivity to chemotherapy, small cell carcinoma remains a difficult-to-treat cancer with a poor prognosis and can rarely be seen originating in organs outside of the lung.     

Heme oxygenase-1: a molecular brake on hepatocellular carcinoma cell migration

Hepatocellular carcinoma (HCC) is a fatal disease with great public health impact worldwide. Heme oxygenase (HO)-1 has recently been reported as an important player in tumor angiogenesis and metastasis. However, the role of HO-1 in liver cancer metastasis is unclear. In this study, we explored genetic differences and downstream signal transduction pathways of HO-1 in liver cancer cell lines. HO-1 wild-type and mutant cell lines were generated from human liver cancer cell line HepG2. The overexpression of wild-type HO-1 decreased the migration of HepG2 cells. In contrast, the overexpression of mutant HO-1G143H increased the migration of the cancer cells. Interleukin (IL)-6 is one of the major downstream molecules that mediated this process because IL-6 expression and migration are suppressed by HO-1 and increased when HO-1 is knocked down by shRNA. In addition, we demonstrated carbon monoxide (CO) and p38MAPK are the cofactors in this signal pathway. In vivo animal model demonstrated HO-1 inhibited the tumor growth. In conclusion, in vitro and in vivo data show HO-1 inhibits the human HCC cells migration and tumor growth by suppressing the expression of IL-6. The heme degradation product CO is a cofactor in this process and inhibits p38MAPK phosphorylation.     

Decrease in mast cells in oral squamous cell carcinoma: possible failure in the migration of these cells

It is becoming accepted that multiple cell types in stromal microenvironment are involved in tumorigenesis. In this setting, mast cells (MC) display a diversity of roles that may contribute to the defense against tumors or tumor progression. Thus, the aim of this study was to evaluate density and migration of MCs in OSCC (oral squamous cell carcinoma) and pre-malignant oral hyperkeratosis (leukoplakia) as well as their relationship with clinical and microscopic parameters. The tryptase and c-kit expression was analyzed in 38 cases of OSCC, 26 cases of leukoplakia, and 12 cases of clinically healthy oral mucosa (control) by means of immunohistochemistry. The tryptase(+) cell numbers were decreased in OSCC (P=0.0003) and leukoplakia (P=0.03) compared with control. Similar numbers of tryptase(+) cells were observed in leukoplakia and OSCC (P=0.31). The density of c-kit(+) MCs was also significantly lower in OSCC and leukoplakia in relation to control resulting in a reduced c-kit(+)/tryptase(+) relationship in OSCC (19%) in comparison with leukoplakia (59%) and control (63%). No correlation was observed between MC populations with clinical and microscopic characteristics of OSCC. Our findings suggest that the decrease in MC numbers in pre-malignant and malignant oral lesions may be related to the migration failure of these cells, possibly reflecting an important modification in the microenvironment during tumor initiation and progression.     

Squamous cell carcinoma of the thyroid

Eight cases of squamous cell carcinoma of the thyroid are reviewed. The clinical features and natural history of our cases are presented. All tumours showed an aggressive biological behaviour. Two patients showed association with well-differentiated thyroid cancer. It is difficult to conclude whether these tumours are de novo occurrences or were a result of a complete replacement of a previously existing condition after a change in histologic character.     

Squamous cell carcinoma and adenosquamous cell carcinoma of the thyroid gland

Two cases of a squamous cell carcinoma and an adenosquamous cell carcinoma of the thyroid gland are presented. Both cases have survived without recurrence for 18 months and 31 months respectively, although these cases have an unfavorable prognosis. A review of the Japanese literature reveals that these two tumors differ significantly in their clinical features. In cases involving a squamous cell carcinoma the ratio of female to male patients is lower, the duration of the illness before treatment is shorter, and the prognosis is poorer than those with an adenosquamous cell carcinoma. These features suggest that the carcinomas have a different histogenesis.     

Visinin-like protein-1 is a potent inhibitor of cell adhesion and migration in squamous carcinoma cells

Tumor cell invasion is a highly integrated and complex process comprising several biologically distinct functions such as cell adhesion, motility, proteolysis, etc. Visinin-like protein-1 (VILIP-1), a member of the neuronal EF-hand calcium-sensor protein family, plays a role in regulating tumor cell invasiveness of mouse squamous cell carcinoma (SCC). VILIP-1 enhances cyclic adenosine monophosphate levels through PKA induction. However, the mechanism by which VILIP-1 reduces cell invasiveness is not well understood. In this study, we show that VILIP-1 decreased cell adhesion and migration/invasiveness of highly invasive mouse SCC cells. Forced expression of VILIP-1 reduced cell adhesion to fibronectin in parallel to downregulating alphav and alpha5 integrin subunit levels. VILIP-1 overexpression also led to decreased migration ability. Conversely, short hairpin RNA-mediated VILIP-1 knock-down of SCC cells' characterized by little or no invasiveness, correlated with increased adhesion to fibronectin and enhanced expression of alphav and alpha5 integrin subunits together with increased cell migration. Function-blocking assays with inhibitory anti-alpha5 and anti-alphav integrin antibodies showed that both subunits contributed to cell adhesion, migration, and invasiveness of highly invasive SCC cell lines. These results point to a critical role of VILIP-1 in regulating cell adhesion and migration by downregulation of fibronectin receptor expression. Decreased or absent VILIP-1 expression in SCC cell subpopulations may lead to a more advanced malignant phenotype characterized by changes in adhesive ability and increased cell motility, suggestive of a tumor suppressor function.     

Squamous cell carcinoma of the thyroid: a report of two cases.

Two patients with squamous cell carcinoma, which accounts for 1.1% of all primary thyroid carcinomas, are described. Squamous metaplasia is the most likely etiology, but an occasional carcinoma may be derived from remnants of embryonic origin. Although squamous metaplasia has been documented in several conditions involving the thyroid, no evidence exists that this predisposes to squamous cell carcinoma. Metastases and direct extension of squamous cell carcinoma in the thyroid gland are much more frequent than primary involvement and are always part of a generalized carcinomatosis. A primary lesion must always be sought; however, diagnosis may not be possible until an initially occult tumor becomes evident or even until autopsy. Because this lesion typically runs a fulminant course, radical surgical resection at the earliest opportunity offers the best hope for cure. The lesions are usually radioresistant, and chemotherapy has not been shown to alter the course of this disease.     

Notch信号通路对肝癌细胞迁移的调控机制研究

目的：探讨Notch信号通路对肝癌细胞迁移的调控机制。方法体外培养HepG2、MHCC97H、Huh-7肝癌细胞株和HL-7702正常肝细胞株,Transwell小室检测细胞迁移能力,蛋白免疫印迹法检测各细胞系Snail、E-cadherin蛋白表达水平,实时定量RT-PCR检测Snail、E-cadherin mRNA表达水平;采用DAPT阻断Notch信号通路,比较其对细胞迁移能力和Snail、E-cadherin蛋白及mRNA表达水平的影响。结果 HepG2、MHCC97H、Huh-7细胞株迁移能力高于HL-7702细胞株（P﹤0.05）,HepG2、MHCC97H、Huh-7肝癌细胞株迁移能力比较差异无统计学意义（P﹥0.05）。HepG2、MHCC97H、Huh-7细胞Snail蛋白及mRNA高于HL-7702细胞,E-cadherin蛋白及mRNA表达低于HL-7702细胞（P﹤0.05）,HepG2、MHCC97H、Huh-7细胞间Snail、E-cadherin蛋白及mRNA表达差异无统计学意义（P﹥0.05）。HepG2、MHCC97H、Huh-7细胞经DAPT处理后迁移能力低于未经DAPT处理的细胞株（P﹤0.05）,HL-7702细胞DAPT处理与未经DAPT处理迁移能力比较差异无统计学意义（P﹥0.05）。DAPT处理后,HepG2、MHCC97H、Huh-7细胞株Snail蛋白及mRNA表达水平降低,E-cadherin蛋白及mRNA表达增加,与未经DAPT处理的细胞株比较差异具有统计学意义（P﹤0.05）,HepG2、MHCC97H、Huh-7细胞间Snail、E-cadherin蛋白及mRNA表达差异无统计学意义（P﹥0.05）。结论 Notch信号通路可能是通过调控Snail、E-cad-herin通路调控肝癌细胞的迁移过程。     

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases,inhibits anaplastic thyroid carcinoma cell proliferation and migration

The tyrosine and phosphoinositide kinases play crucial roles in the regulation of many cancer cell processes including cell survival and cell motility. Anaplastic thyroid carcinoma (ATC) is a rare and deadly type of thyroid cancer, and so far, there are no effective therapeutic compounds for ATC. Herein, we investigate the anticancer activities of PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, in ATC therapy. We found that PP121 is effective at suppressing cell viability, inducing cell apoptosis, and inhibiting cell migration and invasion. The potential anticancer mechanism for PP121 might be its inhibitory effects on phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in ATC cells. Furthermore, PP121 is effective at suppressing ATC tumor growth in vivo. In summary, our studies suggest that PP121 might be a promising therapeutic compound for ATC treatment, which might shed new light on ATC therapy.     

肝素酶介导的肝癌细胞与血管内皮细胞黏附及穿内皮迁移

目的:探讨肝素酶(heparanase,HPSE)对肝细胞癌(hepatocellular carcinoma,HCc)细胞与血管内皮细胞黏附及穿内皮迁移的影响.方法:选用人正常脐静脉内皮细胞株HUVEC-C,肝LO-2细胞,肝癌HepG2、BEL-7402和HCCLM3细胞,用Real-time PCR筛选高表达HPSE的HCC细胞;设计4个HPSE基因RNA干扰(RNA interference,RNAi)序列、构建质粒,并筛选出最优RNAi质粒;用该RNAi质粒转染高表达HPSE的HCC细胞,同时设空白对照组、阴性对照组和未转染的HCC细胞组;黏附试验观察各组HCC细胞与HUVEC-C细胞的黏附情况;Transwell小室法观察HCC细胞穿HUVEC-C细胞迁移情况;癌细胞均以0.25％玫瑰红染色、光镜下观察;酶标仪法分别测定脱色后各组细胞D值并分析比较.结果:HCCLM3细胞HPSEmRNA表达水平显著高于肝LO-2、HepG-2和Bel-7402细胞[(5.72±0.62) vs (1.05 ±0.09)、(2.65±0.31)和(3.43±0.58),均P＜0.01)l;设计的4个HPSE之RNAi载体,以siHPSE-3158对HPSE基因表达的抑制效果最佳(P＜0.05).RNAi组HCCLM3细胞与HUVEC-C细胞黏附率显著低于空白对照组、阴性对照组和未转染的HCCLM3细胞组[(0.31 ±0.04) vs (0.46±0.06)、(0.45 ±0.05)和(0.64±0.09),均P＜0.01)].RNAi组HCCLM3细胞穿HUVEC-C细胞迁移率也显著低于空白对照组、阴性对照组和未转染的HCCLM3细胞组[(0.28 ±0.03) vs (0.41 ±0.04)、(0.41±0.05)和(0.43±0.05),均P＜o.05)].结论:HPSE参与介导HCC细胞与血管内皮细胞的黏附及HCC细胞穿内皮迁移,可能是HCC微血管捕获、血行转移的重要因素.     

Transition of oxic cells to hypoxic cells in a murine squamous cell carcinoma

(125I) Iododeoxyuridine labeling of a squamous cell carcinoma and follow-up of 125I activity at the tumor in situ revealed that the 125I activity remained at a constant level from the 24th to the 100th hour post-labeling and then decreased with a half time of about 200 hr. Autoradiographic studies with (3H) thymidine showed that the tumor cells were labeled around capillaries, spread through the corded structure (the cord) and finally reached the necrotic regions. One could speculate that the constant 125I period represents the transit time of the labeled cells through the cord and that the decline occurs mostly in the necrotic regions.     

Reduced E-cadherin expression is an indicator of unfavourable prognosis in oral squamous cell carcinoma

The aim was to evaluate E-cadherin expression in oral squamous cell carcinoma, and its possible relationships with tumour histology and with clinical course and survival. Surgical biopsies from 47 cases of oral squamous cell carcinoma were analysed for expression of E-cadherin using immunohistochemistry. Statistical analyses were performed to identify possible associations with tumour clinic-histological features and with clinical course and survival. Weak or absent E-cadherin expression was associated with a more invasive histological pattern and with metastasis to the cervical lymph nodes. Uni- and multivariate analyses indicated that weak or undetectable E-cadherin expression is an indicator of shorter disease-free period and shorter survival time. Reduced E-cadherin expression in oral squamous cell carcinoma is associated with more aggressive tumour behaviour and worse prognosis.