Biomedical subjects

Fulvio Basolo

Publications and source records attributed to Fulvio Basolo.

At least 19 recordsLinked to original sources

PubMed2006

Expression of endothelin 1 and its angiogenic role in meningiomas.

Meningiomas are one of the most frequent central nervous system tumours. Although slow-growing at times, they continue to be a cause of morbidity and mortality. The endothelin (ET) family consists of three isoforms: ET-1 is the most abundant one. ET-1 may be involved in meningioma tumourigenesis in concert with other growth factors, in particular with angiogenic agents. We analysed ET-1 expression by immunohistochemistry and its activating system by reverse-transcription-polymerase chain reaction in 56 cases of meningioma. We found an association between high-grade meningiomas and high ET-1 expression levels (p=0.002). Moreover, we evaluated the potential angiogenic role of ET-1, finding an elevated microvessel count in tumours with high ET expression levels (p=0.004). ET-1 may contribute to meningioma growth by inducing formation of new blood vessels. The finding that ET-1 expression positively correlates with vascular endothelial growth factor (VEGF) expression in meningiomas (p=0.03) also supports the hypothesized modulating effect of ET-1 on angiogenesis. Thus, the influence of the ET system on the progression of meningiomas may occur through stimulation of VEGF. The association of ET-1 and meningioma represents a potential area for therapeutic intervention with selective ET inhibitors. Additional clinical studies will be needed before inhibitors can be incorporated in clinical practice.

Adult↗

PubMed2006

Treatment with drugs able to reduce iodine efflux significantly increases the intracellular retention time in thyroid cancer cells stably transfected with sodium iodide symporter complementary deoxyribonucleic acid.

CONTEXT: One of the major limits of gene therapy with sodium iodide symporter (NIS), which enables cells to be subjected to radioiodine therapy, is that NIS-transfected cells rapidly release the intracellular iodine. METHODS: We transfected human anaplastic (FRO) and medullary (TT) thyroid cancer-derived cell lines that were unable to take up iodine with human NIS cDNA. The possibility of increasing the iodine retention time by treating the transfected clones with myricetin, lithium, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) was explored. RESULTS: We obtained 19 FRO and 16 TT clones stably transfected with NIS. Twelve of 19 FRO and nine of 16 TT clones expressed the full-length NIS mRNA; 11 of 12 FRO and four of nine TT clones were able to take up radioiodine and correctly expressed NIS protein on the plasma membrane. Kinetic analysis of iodide uptake in the two clones (FRO-19 and TT-2) with the highest uptaking activity revealed that the plateau was reached after 30 min by FRO-19 and after 60 min by TT-2. The t(1/2) of the iodide efflux was 9 min in FRO-19 and 20 min in TT-2. The treatment of the two cell lines with four different drugs revealed that DIDS and 17-AAG, but not myricetin and lithium, significantly increased the intracellular iodide retention time in FRO-19, but not in TT-2. CONCLUSIONS: We showed that 17-AAG and DIDS prolong the retention time of (131)I in NIS-transfected thyroid tumoral cells, thus reinforcing the hope of using this approach for future clinical application, especially in patients with thyroid carcinoma who are no longer responsive to conventional therapy.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2006

Incidental thyroid carcinoma in a large series of consecutive patients operated on for benign thyroid disease.

BACKGROUND: The diagnosis of incidental thyroid carcinoma (ITC) in patients operated on for a benign disease is frequent. This study aims to determine both its clinical effect and the possibility of identifying this class of patients preoperatively. METHODS: A total of 998 consecutive patients (697 women and 301 men; mean age, 49.5 years) undergoing surgery for benign thyroid pathology in a single institution were studied. The mean time between first diagnosis of thyroid disease and operation was 9.0 years (range, 0-50 years). All patients underwent at least one ultrasonography before surgery, and 678 patients underwent fine-needle aspiration cytology. Patients with undetermined cytology or follicular nodules were excluded from the study. RESULTS: Histology revealed an ITC in 104 patients (10.4%): 99 had a papillary carcinoma. Mean and median diameters of ITC were 1.4 and 0.7 cm, respectively (range, 0.1-7.5 cm). In 43 patients, the tumour size was greater than 1 cm, whereas it exceeded 2 cm in 25 patients. Tumours were multicentric in 19.8% of the patients and occurred in 8.2% of patients with nodular toxic goiter, 8.7% of patients with toxic diffuse goiter and 13.8% of patients with multinodular goiter. DISCUSSION: The results confirm the high frequency of ITC. ITC was more frequent in euthyroid patients than in thyrotoxic patients (P < 0.03). Sex, age, thyroid volume and interval between diagnosis and surgery did not significantly influence its incidence. The majority of ITC was represented by microcarcinomas, but in approximately 25% of patients, the tumour size was greater than 2 cm. The role played by FNAC in excluding malignancies proved to be fairly inconclusive.

Adolescent↗

PubMed2006

Tumour necrosis factor-alpha: prognostic role and relationship with interleukin-8 and endothelin-1 in non-small cell lung cancer.

Cytokines mediate numerous physiological and immune reactions, which are manifested in various biological effects, including tumouricidal activity. We evaluated the expression of the pleiotropic cytokine, tumour necrosis factor-alpha (TNF-alpha), by competitive PCR technique in 47 non-small cell lung cancer (NSCLC) cases and the impact of TNF-alpha on their clinical behaviour. Using univariate analysis, our study demonstrated a positive correlation between high TNF-alpha expression and favourable prognosis in NSCLC in terms of overall survival and disease free interval (p=0.03 and 0.04, respectively) and TNF-alpha maintained its independent role in multivariate analysis. TNF-alpha can stimulate the expression of many molecules, including interleukin-8 (IL-8) and endothelin-1 (ET-1); in our study, the expression of TNF-alpha was significantly associated with high IL-8 mRNA levels (p=0.008) and ET-1 mRNA positivity (p=0.03). We suggested that TNF-alpha can induce ET-1 mRNA expression in NSCLC, similarly to IL-8 expression. Our study may also contribute to advancing the knowledge of the molecular relationship between cytokines and endothelial functions in NSCLC.

Adult↗

PubMed2005

Expression of endothelin-1 is related to poor prognosis in non-small cell lung carcinoma.

The endothelin (ET) system influences tumourigenesis and tumour progression by various mechanisms, including angiogenesis. The aim of this study was to determine whether the expression of endothelin-1 (ET-1) is related to the angiogenic phenomenon in lung cancer and whether it could be involved in its clinical behaviour. Expression of ET-1, endothelin-converting enzyme-1 (ECE-1) and endothelin-receptors ETA and ETB was examined in 201 non-small cell lung carcinoma (NSCLC) and corresponding normal tissues using real-time polymerase chain reaction (RT-PCR). Forty NSCLC were also analysed for vascular endothelial growth factor (VEGF) expression by a competitive-PCR approach to assess whether ET-1 expression was related to this angiogenic factor. A higher number of cases with ET-1, ECE-1 and ETA mRNA expression was observed in malignant lung tumours compared with normal lung tissues (45.7% versus 33% for ET-1 (P < 0.0001); 38.3% versus 16.5% for ECE-1 (P = 0.004); and 42.8% versus 28.5% for ETA (P < 0.0001)). On the other hand, ETB mRNA was higher in normal lung tissues than in tumour samples (58.5% versus 52.8% (P < 0.0001)). Immunohistochemical analysis was also performed in 78 cases, selected from among those with high ET-1 mRNA, to confirm the presence of ET-1 protein and to determine its distribution and localisation. Moreover, an interesting relationship was observed between ET-1 and VEGF mRNA levels (P = 0.02). At univariate analysis, clinical-pathological parameters, such as sex, nodal metastatic involvement and stage, and ET-1 expression were seen to be significant predictors of worse prognosis regarding both overall survival (P = 0.001, P = 0.0003, P = 0.001 and P = 0.03, respectively) and disease-free interval (P = 0.0005, P = 0.0007, P = 0.001 and P = 0.04, respectively). We conclude that ET-1 could be involved in angiogenic phenomena in NSCLC and may represent a further indicator of progression and poor prognosis in this type of cancer, with interesting therapeutic implications.

Adult↗

PubMed2005

Osteopontin expression and prognostic significance in non-small cell lung cancer.

PURPOSE: The survival rate of non-small cell lung cancer patients is very low, and knowledge of predictors of outcome is inadequate. To improve the curability of lung cancer, we need to identify new specific molecules involved in tumorigenesis and progression. The purpose of this study was to better define the role of osteopontin in non-small cell lung cancer biology by determining its prognostic significance. EXPERIMENTAL DESIGN: Osteopontin expression was evaluated by immunohistochemistry, as percentage of neoplastic cells with cytoplasmic immunoreactivity, in a wide series of patients with stage I-IIIA non-small cell lung cancer (207 cases). The median value of this series (20% of positive cells) was used as the cutoff value to distinguish tumors with low (<20%) from tumors with high (> or =20%) osteopontin expression. RESULTS: Taking the series of patients as a whole (207 cases), osteopontin expression was associated with neither overall survival (P = 0.14) nor disease-free survival (P = 0.074). However, among patients with at least 6 years of follow-up (163 cases), 6-year overall survival and disease-free survival were significantly reduced if osteopontin expression was high (P = 0.0085 for overall survival, P = 0.0023 for disease-free survival). Moreover, a statistically significant correlation between high levels of osteopontin and shorter overall survival (P = 0.034) and disease-free survival (P = 0.011) in patients with stage I tumors (136 cases) was shown. CONCLUSIONS: Our results support the hypothesis of an association between high osteopontin expression and poor survival of patients with stage I non-small cell lung cancer, suggesting that osteopontin could be a candidate target for cancer therapy.

Adult↗

PubMed2005

Interleukin-8 in non-small cell lung carcinoma: relation with angiogenic pattern and p53 alterations.

Progression of solid tumors, including NSCLC, is associated with increase in MVC (microvessel count), as a measure of tumor angiogenesis resulting from an imbalance between angiogenic factors and inhibitors. However, since tumor angiogenesis is a multi-step process under the control of various molecules, the mechanism of angiogenesis has not been fully clarified. Interleukin (IL)-8 has been shown to have a potential angiogenic effect in vitro and in vivo, and is overexpressed in several human solid cancers. Among the various angiogenic factors, vascular endothelial growth factor (VEGF) has been shown to correlate with a high MVC and with adverse prognosis in several human cancers, including NSCLC. Alterations of p53 suppressor gene are the most common genetic changes found in malignant tumors; several studies examined the link between aberrant p53 and angiogenesis in lung cancer, but only a few studies report data regarding a relation between p53 mutations and IL-8 expression. In this study we observed a correlation between IL-8 mRNA expression, intratumoral MVC and VEGF mRNA expression levels; furthermore, an aberrant p53 status was related to IL-8 expression. However, in our samples IL-8 levels did not significantly affect prognosis of NSCLC; more studies are required to elucidate the precise role of IL-8 in a large series of patients with non-small cell lung carcinoma.

Adenocarcinoma↗

PubMed2005

Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness.

UNLABELLED: The transmembrane glycoprotein CD44v6 is overexpressed in most papillary thyroid carcinomas (PTC). We previously reported that osteopontin (OPN), a secreted glycoprotein that functions as a ligand for CD44v6, is overexpressed in thyrocytes transformed by the RET/PTC oncogene. OBJECTIVE: In this study we asked whether OPN is overexpressed in human PTC samples, and whether its expression correlates with clinical and histological features of the tumors. Furthermore, we wanted to establish the functional role of the CD44-OPN axis in thyroid tumorigenesis. DESIGN: Thyroid samples from 117 patients who had undergone surgical resection of the thyroid gland for benign or malignant lesions were collected. OPN and CD44 expressions were evaluated by immunohistochemistry with specific monoclonal antibodies. OPN expression was correlated with different PTC histological variants, lymph node metastasis, and PTC size. RESULTS: In this study we show that OPN is overexpressed in human PTCs with respect to normal thyroid tissue, follicular adenomas, and multinodular goiters (P < 0.05). The prevalence and intensity of OPN staining were significantly correlated with the presence of lymph node metastases (P = 0.0091) and tumor size (P = 0.0001). We also show that treatment of human PTC cells with recombinant exogenous OPN stimulated Matrigel invasion and activated the ERK and V-AKT murine thymoma viral oncogene homolog 1/protein kinase B; signaling pathways. Blockage of anti-CD44 antibodies prevented these effects. CONCLUSIONS: Given its prevalence and its correlation with aggressive features of human PTCs, we suggest that OPN might be used as a diagnostic and prognostic marker for these tumors. Furthermore, given the role of the OPN-CD44v6 axis in PTC cells, we suggest that CD44 and/or OPN may be molecular targets for therapeutic intervention in aggressive PTCs.

Carcinoma, Papillary↗

PubMed2005

Mitogenic effects of the up-regulation of minichromosome maintenance proteins in anaplastic thyroid carcinoma.

CONTEXT: Anaplastic thyroid carcinomas (ATC) are among the most aggressive human malignancies and are characterized by high mitotic activity. Minichromosome maintenance proteins (MCM) 2-7 are required to initiate eukaryotic DNA replication, and their overexpression has been associated with dysplasia and malignancy. OBJECTIVE: In an attempt to cast light on the mechanisms governing ATC, we evaluated MCM5 and MCM7 expression in human normal, papillary (PTC), and anaplastic thyroid samples, as well as in primary culture cells and transgenic mouse models. RESULTS: MCM5 and MCM7 expression was high in 65% of ATC and negligible in normal thyroid tissue and papillary thyroid carcinomas. In ATC, high MCM5 and MCM7 expression was paralleled by high levels of MCM2 and MCM6. An analysis of human ATC primary cell cultures and of a transgenic mouse model of ATC confirmed these findings. An increased transcription rate accounted for MCM7 up-regulation, because the activity of the MCM7 promoter was more than 10-fold higher in ATC cells compared with normal thyroid cells. Adoptive overexpression of wild-type p53, but not of its inactive (R248W and R273H) mutants, strongly down-regulated transcription from the MCM7 promoter, suggesting that p53 knock-out contributes to MCM7 up-regulation in ATC. Treatment with small inhibitory duplex RNAs, which decrease MCM7 protein levels, reduced the rate of DNA synthesis in ATC cells. CONCLUSION: MCM proteins are overexpressed in ATC and sustain the high proliferative capacity of ATC cells.

Animals↗

PubMed2005

Proliferative activity of extracellular HIV-1 Tat protein in human epithelial cells: expression profile of pathogenetically relevant genes.

BACKGROUND: Tat is being tested as a component of HIV vaccines. Tat activity has been mainly investigated on cells of lymphoid/hematopoietic lineages. HIV-1, however, is known to infect many different cells of both solid organs and mucosal surfaces. The activity of two-exon (aa 1-101) and synthetic (aa 1-86) Tat was studied on mammary and amniotic epithelial cells cultured under low serum conditions. RESULTS: small concentrations of Tat (100 ng/ml) stimulated cell proliferation. Tat antibodies neutralized the mitogenic Tat activity. Changes of gene expression in Tat-treated cells were evaluated by RT-PCR and gene-array methods. Within 4 hours of treatment, exposure to Tat is followed by up-regulation of some cell cycle-associated genes (transcription factors, cyclin/cdk complexes, genes of apoptotic pathways) and of genes relevant to HIV pathogenesis [chemokine receptors (CXCR4, CCR3), chemotactic cytokines (SDF-1, RANTES, SCYC1, SCYE1), IL6 family cytokines, inflammatory cytokines, factors of the TGF-beta family (TGFb, BMP-1, BMP-2)]. Up-regulation of anti-inflammatory cytokines (IL-10, IL-19, IL-20), a hallmark of other persistent viral infections, was a remarkable feature of Tat-treated epithelial cell lines. CONCLUSION: extracellular Tat is mitogenic for mammary and amniotic epithelial cells and stimulates the expression of genes of pathogenetic interest in HIV infection. These effects may favor virus replication and may facilitate the mother-to-child transmission of virus.

Cell Cycle↗

PubMed2005

The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells.

In papillary thyroid carcinomas (PTCs), rearrangements of the RET receptor (RET/PTC) and activating mutations in the BRAF or RAS oncogenes are mutually exclusive. Here we show that the 3 proteins function along a linear oncogenic signaling cascade in which RET/PTC induces RAS-dependent BRAF activation and RAS- and BRAF-dependent ERK activation. Adoptive activation of the RET/PTC-RAS-BRAF axis induced cell proliferation and Matrigel invasion of thyroid follicular cells. Gene expression profiling revealed that the 3 oncogenes activate a common transcriptional program in thyroid cells that includes upregulation of the CXCL1 and CXCL10 chemokines, which in turn stimulate proliferation and invasion. Thus, motile and mitogenic properties are intrinsic to transformed thyroid cells and are governed by an epistatic oncogenic signaling cascade.

Animals↗

PubMed2005

Advanced stage thymomas and thymic carcinomas: results of multimodality treatments.

BACKGROUND: With the aim of evaluating the results of multidisciplinary approaches, we reviewed our experience in multimodality treatment of advanced stage (III and IVA) thymic tumors. METHODS: From 1976 to 2003, 56 patients with Masaoka stage III and IVA thymic tumors underwent a multimodality treatment. Thirty-six patients underwent neoadjuvant chemotherapy, surgery, and postoperative radiotherapy; 20 patients were treated by primary surgery and postoperative radiotherapy (n = 12), chemotherapy (n = 1) or chemoradiotherapy (n = 7). The neoadjuvant or adjuvant chemotherapy consisted of three courses of cisplatin, epidoxorubicin, and etoposide every 3 weeks. Adjuvant radiotherapy consisted of 45 Gy for complete resections or 60 Gy for incomplete resections. RESULTS: The preoperative diagnosis of invasive thymomas was performed in a total of 29 cases: 15 by mediastinotomy, 6 by video-assisted thoracoscopic surgery, and 8 by fine-needle aspiration. In 27 cases no diagnosis was available, but in most of them a thymus-related syndrome was present. Thirty-four patients are still alive (31 disease-free), and 22 have died (2 disease-free). Ten-year survival was 48% and 45.7% for stage III and IVA thymomas, respectively. The presence of myasthenia gravis (p = 0.04) and neoadjuvant chemotherapy (p = 0.004) affected survival significantly. CONCLUSIONS: The multimodality treatment of stage III and IVA thymic tumors allows a good long-term outcome; the neoadjuvant chemotherapy improves the resectability rate and the survival of both stages of the disease.

Adult↗

PubMed2004

All-trans-retinoic acid treatment inhibits the growth of retinoic acid receptor beta messenger ribonucleic acid expressing thyroid cancer cell lines but does not reinduce the expression of thyroid-specific genes.

Conventional chemotherapy and radiotherapy are ineffective for the treatment of advanced thyroid tumors like poorly differentiated papillary, anaplastic, and medullary thyroid cancer. In the attempt to evaluate the possibility of using retinoic acid (RA) in the treatment of thyroid cancer refractory to conventional therapy, we studied the effect of all-trans-RA treatment on five human thyroid cancer cell lines. We found that WRO and NPA, derived from follicular and poorly differentiated human thyroid carcinoma, respectively, showed a growth inhibition after 25 and 21 d of RA treatment. Both apoptosis and a decrease in DNA synthesis were observed as mechanisms of growth inhibition. In the NPA cell line, a delay of cell-cycle progression has also been observed. On the contrary, we did not observe any recovery of mRNA expression of thyroid-specific genes and in particular of the sodium iodide symporter gene. The lack of recovery of radioiodide uptake after all-trans-RA treatment confirmed the inability to reexpress sodium iodide symporter mRNA. The main difference between the all-trans-RA responding cells (WRO and NPA) and the nonresponding cells [ARO, FRO (derived from human anaplastic thyroid tumors) and TT (derived from human medullary thyroid tumor)] was the basal and all-trans-RA induced RA receptor (RAR)beta mRNA expression. Interestingly, 14 thyroid tumors (10 papillary and four anaplastic) showed a significant lower expression of RARbeta mRNA when compared with normal thyroid tissues. In agreement with this result, only 30% of papillary thyroid carcinomas analyzed were positive for RARbeta protein expression with a degree of expression that was much lower than that found in normal thyroid tissue. In conclusion we found that all-trans-RA treatment can determine a significant in vitro growth inhibition especially in differentiated thyroid tumor-derived cell lines but it seems unable to reinduce the expression of thyroid-specific genes and in particular to reinduce the ability to take up iodine. The growth inhibition is likely due to apoptosis in an early phase and to a decrease of DNA synthesis later. In some cases, a delay of the cell-cycle progression also may be responsible for the growth inhibition. The finding of a basal and RA-induced RARbeta mRNA expression only in cell lines responding to all-trans-RA suggests that the growth inhibition might be mediated by RARbeta.

Cell Line, Tumor↗

PubMed2004

Functional expression of the CXCR4 chemokine receptor is induced by RET/PTC oncogenes and is a common event in human papillary thyroid carcinomas.

To identify genes involved in the transformation of thyroid follicular cells, we explored, using DNA oligonucleotide microarrays, the transcriptional response of PC Cl3 rat thyroid epithelial cells to the ectopic expression of the RET/PTC oncogenes. We found that RET/PTC was able to induce the expression of CXCR4, the receptor for the chemokine CXCL12/SDF-1alpha/beta. We observed that CXCR4 expression correlated with the transforming ability of the oncoprotein and depended on the integrity of the RET/PTC-RAS/ERK signaling pathway. We found that CXCR4 was expressed in RET/PTC-positive human thyroid cancer cell lines, but not in normal thyroid cells. Furthermore, we found CXCR4 expression in human thyroid carcinomas, but not in normal thyroid samples by immunohistochemistry. Since CXCR4 has been recently implicated in tumor proliferation, motility and invasiveness, we asked whether treatment with SDF-1alpha was able to induce a biological response in thyroid cells. We observed that SDF-1alpha induced S-phase entry and survival of thyroid cells. Invasion through a reconstituted extracellular matrix was also supported by SDF-1alpha and inhibited by a blocking antibody to CXCR4. Taken together, these results suggest that human thyroid cancers bearing RET/PTC rearrangements may use the CXCR4/SDF-1alpha receptor-ligand pathway to proliferate, survive and migrate.

Carcinoma, Papillary↗

PubMed2004

Expression and mutational status of c-kit in small-cell lung cancer: prognostic relevance.

PURPOSE: The c-kit protein, also known as CD117, is a member of the type III receptor tyrosine kinase family. Kinase activity has been implicated in the pathophysiology of many tumors, including small-cell lung carcinoma (SCLC). Autocrine or paracrine activation of c-kit by its ligand has been postulated for lung cancer, but this receptor can also be activated by mutations of the c-kit gene. We examined c-kit expression and mutational status in SCLC to verify its putative expression and genetic alterations, as well as its eventual prognostic impact. EXPERIMENTAL DESIGN: We studied 60 SCLC samples to determine the mutations of the coding region of the gene; the exons 9 and 11 were analyzed by PCR-single-strand conformational polymorphism and automated sequencing. Moreover, c-kit expression was evaluated in 55 samples by immunohistochemical method. RESULTS: Expression of c-kit was demonstrated in about 40% of SCLC samples. Two mutations in exon 9 and three mutations in exon 11 were found. Kaplan-Meier analysis revealed no prognostic significance of c-kit expression for survival. CONCLUSIONS: In our series, the expression of c-kit and its mutational status failed to appear relevant or to have a significant impact on survival; this makes the therapeutic approach with an inhibitor of tyrosine kinase more difficult in SCLC until a sure demonstration of c-kit implication is obtained for this tumor.

Adult↗

PubMed2004

Autocrine stimulation by osteopontin plays a pivotal role in the expression of the mitogenic and invasive phenotype of RET/PTC-transformed thyroid cells.

Papillary thyroid carcinomas are characterized by rearrangements of the RET receptor tyrosine kinase generating RET/PTC oncogenes. Here we show that osteopontin (OPN), a secreted glycoprotein, is a major RET/PTC-induced transcriptional target in PC Cl 3 thyroid follicular cells. OPN upregulation depended on the integrity of the RET/PTC kinase and tyrosines Y1015 and Y1062, two major RET/PTC autophosphorylation sites. RET/PTC also induced a strong overexpression of CD44, a cell surface signalling receptor for OPN. Upregulation of CD44 was dependent on RET/PTC Y1062, as well. Constitutive OPN overexpression or treatment with exogenous recombinant OPN sharply increased proliferation, Matrigel invasion and spreading in collagen gels of RET/PTC-transformed PC Cl 3 cells. These effects were impaired by the treatment of PC Cl 3-RET/PTC cells with OPN- and CD44-locking antibodies. Thus, RET/PTC signalling triggers an autocrine loop involving OPN and CD44 that sustains proliferation and invasion of transfomed PC Cl 3 thyrocytes.

Carcinoma, Papillary↗

PubMed2004

Applications of tissue microarray technology in immunohistochemistry: a study on c-kit expression in small cell lung cancer.

Tissue microarray technology allows the immediate evaluation of molecular profiles of numerous different tissues, with savings of money and time. It was created for rapid, large-scale molecular studies, and the main concern regarding its possible broad acceptance is that the analysis of tissue microarrays instead of whole tissue sections may lead to false negative or positive results because of tissue heterogeneity. In the present study, we analyzed in 54 small cell lung cancers, by immunohistochemistry, the expression of the antigen c-kit, which seems to be important in these neoplasms' tumorigenesis, and compared the staining obtained on whole sections with that of the corresponding tissue microarrays. Although c-kit expression of the whole sections agreed with that of the corresponding biopsies in many cases, the correlation between whole sections and all the companion nonlost single cores or their mean value turned out to be highly significant only if the 36 double negatives (ie, both whole sections and companion tissue microarrays negative) were included (P <0.0001). In fact, if only cases positive to at least 1 of the tests (i.e. whole sections or corresponding tissue microarrays positive) were considered, the correlation was not significant (P=0.055). Tissue microarrays showed a good specificity (94.2% for all single cores and 92.3% for their mean value) but a rather poor sensitivity (respectively, 69.4% and 71.4%). Moreover, a high percentage (13.4%) of cores was lost, and this loss was not random. To sum up, in our experience, tissue microarray technology cannot be a substitute for whole sections in clinical diagnosis of individual cases.

Adult↗

PubMed2004

Medullary and papillary tumors are frequently associated in the same thyroid gland without evidence of reciprocal influence in their biologic behavior.

Papillary thyroid microcarcinoma (mPTC), is a very frequent incidental finding with a frequency varying from a few percent to 35% at postmortem histopathologic examinations. However, the presence of mPTC in patients undergoing thyroidectomy for multinodular goiter (MNG) and for Graves' disease (GD) has been found to be lower. Patients with medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) association have been published as anecdotal case reports, as well as kindred with familial MTC or multiple endocrine neoplasia (MEN) 2A with some members simultaneously affected by MTC and PTC. We studied the prevalence and the biological behavior of MTC associated with PTC, with particular attention to those cases in which a mPTC was incidentally found. Twenty-seven of 196 (13.8%) MTC cases showed an association with PTC and in particular 21 of 190 (11.05%) with an incidental mPTC. This percentage is higher than that reported in the literature on the association of mPTC with GD (2.8%-4.5%) and MNG (3%). Also the percentage of the more general association of MTC/PTC, not restricted to mPTC, found in our series (13.8%) is higher than that reported in studies that analyzed the prevalence of PTC (any size) in patients treated for MNG (7.5%). A similarly high percentage of MTC/PTC had not been reported before and in particular there are no reports on large series of MTC/PTC. We also analyzed the epidemiologic, clinical, and pathologic features of MTC associated and not associated with PTC without finding any difference. In particular the outcome of the MTC did not appear to be influenced by the presence of the PTC and the specific radioiodine treatments. Moreover, although we cannot completely exclude a shared pathogenic event as the cause of both MTC and PTC, the molecular analysis of RET gene alterations did not show any common mutation.

Adult↗