Rapid and sensitive detection of messenger RNA expression for molecular differential diagnosis of renal cell carcinoma.
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PURPOSE: The aim of this study was to develop a practical technique to detect mRNA expression and to validate a panel of mRNA markers for molecular differential diagnosis of renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: The renal cancer cell line SKRC-52 was used to set up the technique, which consisted of column extraction of RNA and one-step reverse transcription-PCR. We validated a panel of gene markers, including MN/CA9, cadherin-6, vimentin, mucin1, and parvalbumin, and studied 50 renal tumors (30 conventional, 9 papillary, and 5 chromophobe RCCs and 6 oncocytomas), 10 normal tissues, and 10 normal blood samples. We mimicked fine needle aspiration (FNA) biopsy in 10 kidneys with conventional RCC and applied this technique to 10 preoperative FNA samples from imaging-indeterminate renal tumors. RESULTS: The technique could detect as few as 10 SKRC-52 cells with MN/CA9 as mRNA marker and was less time consuming and labor intensive. MN/CA9 was a sensitive and rather specific gene marker for conventional RCC. Cadherin-6 gene expression was a sensitive marker for conventional and papillary RCC. Vimentin was highly specific for conventional RCC. Mucin1 mRNA was sensitive for papillary and chromophobe RCC and oncocytoma. Parvalbumin mRNA was a sensitive and highly specific marker for both chromophobe RCC and oncocytoma. Thus, these mRNA markers represent the biomarker genes for the subtypes of renal tumors. Finally, we successfully applied the technique to FNA specimens. Five preoperative FNA samples were MN/CA9 gene positive, suggesting a RCC, whereas the routine cytology was positive in only three cases. CONCLUSIONS: A rapid and sensitive assay of mRNA markers was developed for molecular differential diagnosis of RCC. This molecular assay can be used as a powerful ancillary to surgical pathological diagnosis and cytological diagnosis of RCC. (+info)
My approach to oncocytic tumours of the thyroid.
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The traditional approach to oncocytic thyroid lesions classified these as a separate entity, and applied criteria that are somewhat similar to those used for follicular lesions of the thyroid. In general, the guidelines to distinguish hyperplasia from neoplasia, and benign from malignant were crude and unsubstantiated by scientific evidence. In fact, there is no basis to separate oncocytic lesions from other classifications of thyroid pathology. The factors that result in mitochondrial accumulation are largely unrelated to the genetic events that result in proliferation and neoplastic transformation of thyroid follicular epithelial cells. The concept of classifying oncocytic lesions, including follicular variant papillary carcinomas, based on nuclear morphology, immunohistochemical profiles, and molecular markers may pave the way for a better understanding of the biology of oncocytic lesions of the thyroid. (+info)
Core I gene is overexpressed in Hurthle and non-Hurthle cell microfollicular adenomas and follicular carcinomas of the thyroid.
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BACKGROUND: Most of the steps involved in the initiation and progression of Hurthle (oncocytic, oxyphilic) cell carcinomas of the thyroid remain unknown. METHODS: Using differential display and semiquantitative RT-PCR we found, among other alterations, overexpression of the gene encoding the Core I subunit of the complex III of the mitochondrial respiratory chain in a follicular carcinoma composed of Hurthle cells. RESULTS: Similar high levels of Core I gene expression were detected in nine follicular carcinomas (seven with Hurthle cell features), in seven microfollicular adenomas (one with Hurthle cell features) and in one micro/macrofollicular adenoma, in contrast to a lower/normal expression in nine papillary carcinomas (three with Hurthle cell features) and five macrofollicular adenomas (one of which displaying Hurthle cell features). No significative correlation was found between Core I overexpression and the proliferative activity of the lesions. CONCLUSIONS: We conclude that Core I overexpression in thyroid tumours is not associated with malignancy, Hurthle cells or proliferative activity. The pathogenetic mechanism linking Core I overexpression to the microfollicular pattern of growth of thyroid tumours remains to be clarified. (+info)
KIT expression in fetal, normal adult, and neoplastic renal tissues.
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BACKGROUND: KIT is a transmembrane tyrosine kinase receptor, expressed in high amounts in various normal cells. In addition, c-kit mutation or activation is a major pathogenetic event in certain tumours (such as gastrointestinal stromal tumours). There are only limited data in the literature on the expression of KIT in normal and neoplastic renal tissues. AIMS: To investigate KIT expression in normal and neoplastic renal tissues. METHODS: KIT expression was evaluated by means of immunohistochemistry in paraffin wax embedded sections from 67 tissue samples. RESULTS: Eight of eight fetal kidneys, and 10 of 10 normal adult kidneys revealed cytoplasmic staining of renal tubules. The three cases of renal dysplasia studied expressed KIT in their normal and aberrant tubules. Two of 13 conventional renal cell carcinomas (RCCs), two of seven papillary type RCCs, four of seven chromophobe type RCCs, none of six nephroblastomas, seven of seven oncocytomas, two of two mesoblastic nephromas, and two of four angiomyolipomas were positive. CONCLUSION: KIT is expressed in normal fetal and adult renal tubules, and in a subset of renal tumours. The expression of KIT in these renal tumours may prove to have diagnostic relevance and/or therapeutic implications. (+info)
A rare case of Hurthle cell carcinoma with endobronchial metastasis.
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Endobronchial metastases (EBM) are frequently seen in breast, renal and colon carcinomas. However, to our knowledge, only one case has ever been reported as EBM secondary to Hurthle cell carcinoma (HCC) in the literature. A 57-year-old woman had a bilateral total thyroidectomy for thyroid mass in 1990 that was diagnosed as HCC. She was admitted to our outpatient clinic in August 1999, with symptoms of cough, sputum, and right-sided pleuritic pain for the last seven months. In the bronchoscopic examination, two endobronchial lesions were seen. Pathological evaluation of the bronchoscopic samples was diagnosed as "Hurthle cell carcinoma" of thyroid. We suggest that, although rare, HCC should be considered in the differential diagnosis of the endobronchial metastasis. (+info)
Evidence for interaction between the TCO and NMTC1 loci in familial non-medullary thyroid cancer.
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BACKGROUND: Familial non-medullary thyroid cancer (fNMTC) is a complex genetic disorder that is more aggressive than its sporadic counterpart. Thus far, three genetic loci have been implicated in susceptibility to fNMTC by linkage analysis. METHODS: We used linkage analysis to test the significance of two of the known susceptibility loci for fNMTC, TCO on 19p13 and NMTC1 on 2q21 in 10 fNMTC families, nine of which present with cell oxyphilia, a rare histological phenotype associated with TCO. Furthermore, we used two-locus linkage analysis to examine the possibility that the TCO and NMTC1 loci interact to increase the risk of NMTC. RESULTS: The 10 families provided evidence for linkage at both TCO and NMTC, with LOD scores of 1.56 and 2.85, respectively. Two-locus linkage analysis, using a multiplicative risk model for the development of NMTC, achieved a maximum LOD of 3.92, with an LOD of 4.51 when assuming 70% of families were linked, indicating that the segregation in these families is consistent with an interaction model. Most of this evidence came from a large Tyrolean family that singularly achieved a two-locus LOD of 3.21. CONCLUSIONS: These results provide further evidence that susceptibility genes for fNMTC exist at 19p13 and 2q21, and furthermore, raise the possibility that in a subset of fNMTC pedigrees, these loci interact resulting in significantly increased risk of NMTC for patients that carry both susceptibility loci. (+info)
Overexpression of KIT (CD117) in chromophobe renal cell carcinoma and renal oncocytoma.
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KIT expression has not been studied substantially in renal tumors. We analyzed the immunohistochemical expression for KIT in 256 conventional renal cell carcinomas (RCCs), 29 chromophobe RCCs, 25 papillary RCCs, 6 collecting duct RCCs, 6 unclassified RCCs, 7 renal oncocytomas, 20 urothelial carcinomas, 7 nephroblastomas, and 23 angiomyolipomas. We found that 24 chromophobe RCCs (83%) and 5 renal oncocytomas (71%) revealed membranous immunoreactivity for KIT while none of the RCCs of other types expressed KIT immunohistochemically. Sporadic cases of urothelial carcinoma and nephroblastoma were focally positive for KIT. All angiomyolipomas were negative. Genomic DNA extracted from the chromophobe RCCs and renal oncocytomas was submitted for polymerase chain reaction and direct sequencing of the juxtamembrane (exons 9 and 11) and tyrosine kinase (exons 13 and 17) domains. No mutation was found. Our results demonstrate that KIT could be a useful immunophenotypic marker for chromophobe RCC and renal oncocytoma; therefore, it has value for the precise classification of renal cortical epithelial tumors. However, the therapeutic relevance of KIT overexpression in these tumors is uncertain owing to the lack of mutations that would lead to constitutive activation of the protein. (+info)
Peroxisome proliferator activated receptor gamma immunohistochemical expression in human papillary thyroid carcinoma tissues. Possible relationship to lymph node metastasis.
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BACKGROUND: Peroxisome proliferator activated receptor gamma (PPARgamma) involvement in thyroid tumorigenesis has recently been studied, especially in follicular neoplasms. Conflicting results concerning the regulation of this receptor in human papillary carcinoma have been reported. Therefore, we quantitatively assessed PPARgamma immunohistochemical expression in papillary carcinoma in comparison with other types of thyroid tumors and we evaluated its relationship with clinical criteria of aggressiveness. MATERIALS AND METHODS: Immunohistochemistry (IHC) was performed on 56 human thyroid papillary carcinomas (PTC), 9 follicular carcinomas (FTC), 20 follicular adenomas (FA) and 18 Hurthle cells adenomas. PTC were divided into subgroups according to some aggressiveness criteria: tumor size, capsular invasion, lymph node metastasis. Immunostaining was semi-quantitatively analyzed using image analysis software. RESULTS: Strong nuclear PPARgamma expression was detected in a large number of PTC (42%), similar to that found in FTC (44%) or FA (63%). Only Hurthle cell adenoma showed a significantly lower proportion of PPARgamma-positive immunoreactivity (11%, p<0.05). Cases of PTC-associated lymph node metastasis showed a higher percentage of PPARgamma-positivity than other case categories (63% vs. 20%), a result which was also noticed when comparing large PTC with infracentimentric tumors (60% vs. 39%, p<0.05). CONCLUSION: These results, combined with recently published data, suggest that the intense PPARgamma immunostaining revealed in PTC could be related to high wtPPARgamma gene levels. Moreover, they corroborate a strong relationship between PPARgamma expression and tumor progression. PPARgamma IHC evaluation is not a valuable differential diagnostic tool for thyroid tumors but it could be a reliable marker of papillary carcinoma aggressiveness and a potential predictor for an eventual therapy by PPARgamma agonists. (+info)