Hyperthyroidism in a patient with TSH-producing pituitary adenoma coexisting with thyroid papillary adenocarcinoma.
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A 27-year-old woman who presented with a left thyroid nodule was found to have hyperthyroidism caused by a syndrome of inappropriate secretion of TSH. The levels of free T3, free T4 and TSH were 9.50 pg/mL, 4.05 ng/dL and 2.16 microU/mL, respectively. Magnetic resonance imaging of the head revealed a pituitary macroadenoma. The TSH response to TRH stimulation was normal and responses of other anterior pituitary hormones to stimulation tests were also normally preserved. Administration of octreotide with iodine successfully reversed hyperthyroidism prior to total resection of pituitary adenoma, which was followed by hemithyroidectomy of the left thyroid five months later. Histologically, the resected pituitary adenoma was a TSH-producing adenoma (TSH-oma) and the thyroid nodule was a papillary adenocarcinoma. Serum TSH diminished to undetectable levels immediately following pituitary adenomectomy but gradually normalized over nine months. Coexistence of a TSH-oma with thyroid cancer is very rare and only two similar cases have previously been documented. This combination raises the possibility that TSH may be involved in tumorigenesis in the thyroid gland. (+info)
Detection of hepatitis C virus RNA sequences in hepatic portal cholangiocarcinoma tissue by reverse transcription polymerase chain reaction.
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OBJECTIVE: To detect hepatitis C virus (HCV) RNA sequences in the hepatic portal cholangiocarcinoma tissues and their relationship. METHODS: RNA was extracted from paraffin-embedded cholangiocarcinoma tissues of 6 patients by guanidinium method, subjected to reverse transcription and then amplified by double PCR technique using nested primers from the highly conserved 5' noncoding region of HCV genome. RESULTS: HCV RNA of 5' NT sequences was found in the hepatic portal cholangiocarcinoma tissues of 5 out of 6 (83%) patients. CONCLUSIONS: HCV RNA sequences present with high infectious rate in cholangiocarcinoma, and reverse transcription polymerase chain reaction (RT-PCR) assay using primers derived from 5' NT region of HCV sequence is most useful in detecting HCV infection. The development of cholangiocarcinoma awaits further studies. (+info)
Heterozygosity for the mouse Apex gene results in phenotypes associated with oxidative stress.
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Apurinic/apyrimidinic endonuclease is a key enzyme in the process of base excision repair, required for the repair of spontaneous base damage that arises as a result of oxidative damage to DNA. In mice, this endonuclease is coded by the Apex gene, disruption of which is incompatible with embryonic life. Here we confirm the embryonic lethality of Apex-null mice and report the phenotypic characterization of mice that are heterozygous mutants for the Apex gene (Apex+/-). We show that Apex heterozygous mutant cells and animals are abnormally sensitive to increased oxidative stress. Additionally, such animals manifest elevated levels of oxidative stress markers in serum, and we show that dietary supplementation with antioxidants restores these to normal levels. Apex+/- embryos and pups manifest reduced survival that can also be partially rescued by dietary supplementation with antioxidants. These results are consistent with a proposed role for this enzyme in protection against the deleterious effects of oxidative stress and raise the possibility that humans with heterozygous mutations in the homologous HAP1 gene may be at increased risk for the phenotypic consequences of oxidative stress in cells. (+info)
Molecular evidence for the independent origin of extra-ovarian papillary serous tumors of low malignant potential.
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BACKGROUND: Molecular data suggest that peritoneal tumors in women with advanced-stage ovarian papillary serous adenocarcinoma are monoclonal in origin. Whether the same is true for ovarian tumors of low malignant potential is not known. We compared peritoneal and ovarian tumors from women with advanced-stage ovarian papillary serous tumors of low malignant potential to determine whether the peritoneal tumors arose from the same clone as the ovarian tumors. METHODS: We studied the clonality of 73 peritoneal and ovarian tumors from 18 women with advanced-stage ovarian papillary serous tumors of low malignant potential. Formalin-fixed, paraffin-embedded tumors and representative normal tissues were sectioned and stained with hematoxylin-eosin, representative sections from separate tumors were manually microdissected, genomic DNA was extracted from the microdissected tumors, and the polymerase chain reaction was used to amplify a CAG polymorphic site in the human androgen receptor locus on the X chromosome to determine the inactivation pattern of the X chromosome and the clonality of the tumors. RESULTS: The pattern of X-chromosome inactivation could be determined from the tumors of 13 of 18 patients. Of the 13 patients, seven (54%) had nonrandom inactivation of the X chromosome, and six of the seven had different inactivation patterns in the peritoneal and ovarian tumors. Three of these patients also had different patterns of nonrandom X-chromosome inactivation in tumors from each ovary. The remaining six patients had random patterns of X-chromosome inactivation in the peritoneal and ovarian tumors. CONCLUSIONS: Our data suggest that peritoneal and ovarian tumors of low malignant potential arise independently. (+info)
Pulmonary epithelioid hemangioendothelioma coexistent with pulmonary metastasis of thyroid cancer.
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We report a 45-year-old man with epithelioid hemangioendothelioma (EH) and simultaneous pulmonary metastasis of thyroid cancer in his lung. Thyroid cancer, and multiple small nodules in both lungs were noted. He underwent total thyroidectomy followed by radiotherapy with 131I. However, 131I scintigraphy showed poor uptake of radionuclide in the nodules, and the size of the nodules remained unchanged. The diagnostic thoracoscopic biopsy showed two types of nodules, some were positive for thyroglobulin and cytokeratin, and others were reactive for factor VIII. The former nodules were diagnosed as pulmonary metastases of thyroid cancer, and the latter EH. (+info)
Mammary epithelial-specific expression of the integrin-linked kinase (ILK) results in the induction of mammary gland hyperplasias and tumors in transgenic mice.
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The integrin linked kinase (ILK) is a cytoplasmic effector of integrin receptors, involved in the regulation of integrin binding properties as well as the activation of cell survival and proliferative pathways, including those involving MAP kinase, PKB/Akt and GSK-3beta. Overexpression of ILK in cultured intestinal and mammary epithelial cells has been previously shown to induce changes characteristic of oncogenic transformation, including anchorage-independent growth, invasiveness, suppression of anoikis and tumorigenicity in nude mice. In order to determine if ILK overexpression can result in the formation of mammary tumors in vivo, we generated transgenic mice expressing ILK in the mammary epithelium, under the transcriptional control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR). By the age of 6 months, female MMTV/ILK mice developed a hyperplastic mammary phenotype, which was accompanied by the constitutive phosphorylation of PKB/Akt, GSK-3beta and MAP kinase. Focal mammary tumors subsequently appeared in 34% of the animals at an average age of 18 months. Given the focal nature and long latency of the tumors, however, additional genetic events are likely required for tumor induction in the MMTV/ILK mice. These results provide the first direct demonstration of a potential oncogenic role for ILK, which is upregulated in human tumors and tumor cell lines. (+info)
STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas.
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Despite the growing awareness of intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas among clinicians, the molecular features of IPMNs have not been well characterized. Previous reports suggest that inactivation of the STK11/LKB1, a tumor-suppressor gene responsible for Peutz-Jeghers syndrome (PJS), plays a role in the pathogenesis of gastrointestinal hamartomas as well as several cancers, including pancreatic adenocarcinoma. Using polymerase chain reaction amplification of five microsatellite markers from the 19p13.3 region harboring the STK11/LKB1 gene, we analyzed DNA from 22 IPMNs for loss of heterozygosity (LOH). LOH at 19p13.3 was identified in 2 of 2 (100%) IPMNs from patients with PJS and 5 of 20 (25%) from patients lacking features of PJS (7 of 22, 32% overall). Sequencing analysis of the STK11/LKB1 gene in these IPMNs with LOH revealed a germline mutation in one IPMN that arose in a patient with PJS and a somatic mutation in 1 of the 20 sporadic IPMNs. None of the 22 IPMNs showed hypermethylation of the STK11/LKB1 gene. These results suggest that the STK11/LKB1 gene is involved in the pathogenesis of some IPMNs. (+info)
Markers of proliferative activity are predictors of patient outcome for low-grade endometrioid adenocarcinoma but not papillary serous carcinoma of endometrium.
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On the basis of pathogenesis, two types of endometrial cancer can be recognized. Type 1 endometrial carcinomas are relatively indolent tumors that develop after prolonged estrogen stimulation, on a background of endometrial hyperplasia. Type 2 endometrial carcinomas are aggressive tumors that are not associated with hyperplasia or estrogen excess. The aim of this study is to evaluate the prognostic significance of tumor proliferative activity in early-stage endometrial cancer by using mitotic index and immunostaining, comparing Type 1 (endometrioid) and Type 2 (papillary serous carcinoma) tumors. The mitotic index, MIB-1, and p53 immunostaining in 39 tumors from patients with low-grade Stage Ia or Ib endometrioid adenocarcinoma; as well as 23 tumors from patients with Stage I papillary serous carcinoma. In low-grade endometrioid adenocarcinoma, mitotic and MIB-1 indices were statistically significant independent prognostic indicators (P =.004 and P =.018, respectively), and both were strongly correlated with p53 expression (P =.01 and P =.006, respectively). The mean mitotic index was 5 mitoses/10 high-power fields, and mean MIB-1 index was 27.5%. There was no significant correlation between mitotic or MIB-1 indices and patient outcome or p53 expression in papillary serous carcinoma. The mean mitotic index was 31 mitoses/10 high-power fields, and mean MIB-1 index was 30.5% in these tumors. p53 expression and proliferative indices are strongly correlated in low-grade endometrioid adenocarcinoma. MIB-1 and mitotic indices are independent prognostic indicators in these tumors. Papillary serous carcinoma of endometrium is rapidly proliferative in tumors even at an early stage, and quantification of proliferative activity in these tumors does not allow prediction of patient outcome. (+info)