TP53 polymorphism may contribute to genetic susceptibility to develop Hashimoto's thyroiditis.

PURPOSE: p53, which is encoded by the tumor suppressor gene TP53, plays a crucial role in the regulation of mechanisms of cell cycle arrest and apoptosis. Some SNPs of TP53, involving a different apoptotic ability of p53, have been associated with increased susceptibility to develop autoimmune diseases as well as cancer. We investigated the genotypic distribution of TP53 exon 4 SNPs in a cohort of Caucasian patients affected by Hashimoto's thyroiditis (HT). METHODS: Peripheral blood for DNA extraction was collected from 109 Caucasian unrelated subjects, 79 HT patients and 30 healthy controls. SNPs analysis was carried out by amplification and sequencing of exon 4 TP53. RESULTS: For the Pro72Arg (rs 1042522) SNP we found these rates in HT patients: 11.4% wild-type C/C (Pro72Pro), 24.0% heterozygous G/C (Pro72Arg), 64.6% homozygous G/G (Arg72Arg). The corresponding rates in healthy controls were 10, 46.7 and 43.3%, respectively. Thus, significantly different were G/C heterozygosity (24.0 vs 46.7 %, p = 0.039) and G/G homozygosity (64.6 vs 43.3%, p = 0.042). These differences were also confirmed when comparing our study population to published Caucasian control groups. The other described SNPs (Pro34Pro rs 11575998, Pro36Pro rs1800370, Pro47Ser rs1800371, and Arg110Leu rs 11540654) were absent or very rare in our study population. CONCLUSIONS: Our preliminary data, the first on a Caucasian population, indicate an increased prevalence of the homozygous genotype Arg/Arg and a decreased prevalence of heterozygous genotype Arg/Pro of rs 1042522 in HT patients compared to controls, suggesting that such SNP may contribute to confer susceptibility to HT.

Quantum maximum entropy principle for fractional exclusion statistics.

Using the Wigner representation, compatibly with the uncertainty principle, we formulate a quantum maximum entropy principle for the fractional exclusion statistics. By considering anyonic systems satisfying fractional exclusion statistic, all the results available in the literature are generalized in terms of both the kind of statistics and a nonlocal description for excluson gases. Gradient quantum corrections are explicitly given at different levels of degeneracy and classical results are recovered when ℏ→0.

Two SERK genes are markers of pluripotency in Cyclamen persicum Mill.

The genetic basis of stem cell specification in somatic embryogenesis and organogenesis is still obscure. SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) genes are involved in embryogenesis and organogenesis in numerous species. In vitro culture of Cyclamen persicum immature ovules provides a system for investigating stem cell formation and maintenance, because lines forming either organs or embryos or callus without organs/embryos are available for the same cultivar and plant growth regulator conditions. The present aim was to exploit this property of cyclamen cultures to understand the role of SERK(s) in stem cell formation and maintenance in somatic embryogenesis and organogenesis in vitro, in comparison with expression in planta. CpSERK1 and CpSERK2 were isolated from embryogenic callus. CpSERK1 and CpSERK2 levels by RT-PCR showed that expression is high in embryogenic, moderate in organogenic, and null in recalcitrant calli. in situ hybridizations showed that the expression of both genes started in clumps of pluripotent stem cells, from which both pre-embryogenic aggregates and organ meristemoids derived, and continued in their trans-amplifying, meristem-like, derivatives. Expression declined in organ meristemoids, in parallel with a partial loss of meristematization. In mature somatic embryos, and in shoot and root primordia, CpSERK1 and CpSERK2 were expressed in meristems, and similar patterns occurred in zygotic embryo and primary meristems in planta. The results point to SERK1 and SERK2 as markers of pluripotency in cyclamen. It is proposed that the high expression of these genes in the trans-amplifying derivatives of the stem cells maintains a pluripotent condition leading to totipotency and, consequently, somatic embryogenesis.

Isolated pancreatic metastasis from melanoma. Case report.

Pancreas is frequently site of isolated metastasis, approximately in the 40% of cases in patient with previous history of malignant neoplasia, more frequently from renal cell carcinoma. The melanoma metastasis can also interest the pancreas in case of disseminated disease (50% of the cases); more rarely the pancreas is site of isolated metastases from melanoma. The treatment of the pancreatic metastases from melanoma is controversial: the therapeutic choices are few and the role of surgery is not well defined. If the metastasis are confined to the pancreas, the surgical treatment can be useful for better long time survival. We report a rare case of melanoma with pancreatic isolated metastasi in a patient with a previous melanotic metastasis to the inguinal lymph nodes without evidence of primitive tumor.

Serum hepatocyte growth factor is increased in Hashimoto's thyroiditis whether or not it is associated with nodular goiter as compared with healthy non-goitrous individuals.

BACKGROUND: Some growth factors and cytokines are known to cooperate with TSH in thyroid nodular growth, but few data are available on their circulating levels in Hashimoto's thyroiditis (HT). AIM: To evaluate in HT patients whether thyroid nodules are associated with variations in serum levels of hepatocyte growth factor (HGF) and interleukin-6 (IL-6). SUBJECTS AND METHODS: Serum levels of HGF and IL-6 were measured by enzyme-linked immunosorbent assay in 176 euthyroid subjects, subdivided into 4 groups: A) HT patients with nodular goiter (no.=42); B) non-goitrous HT patients (no.=36); C) non-HT patients with nodular goiter (no.=48), and D) healthy subjects without thyroid disease (no.=50). RESULTS: The highest concentrations of serumHGF were found in patients with nodular goiter, irrespective of the presence of associated HT (groups A and C). Nevertheless, in group A serum HGF levels were significantly higher than in group C (860.8+/-333.6 pg/ml vs 691.5+/-156 pg/ml, p<0.01). Moreover, though serum HGF levels in group B (578.3+/-217 pg/ml) were lower than in group A, they were significantly higher than in healthy controls (group D, 512.7+/-170.4 pg/ml, p<0.001). Serum IL-6 levels were similar in the two HT groups (A and B), and increased with respect to groups C and D. CONCLUSIONS: Serum HGF is increased in HT, especially associated to thyroid nodules, as compared with healthy non-goitrous individuals.

The new era of vaccines: the "nanovaccinology".

Vaccinations are the most effective preventive methods against infectious diseases and represent one of the most relevant successes of medicine. Vaccine development is constantly evolving; therefore, the number of vaccine candidates is progressively increasing. However, most of new potential vaccines are characterized by a lower immunogenicity, with the inability to stimulate powerful and long-lasting immune responses. Hence, to get modern and effective vaccines, we need adjuvants and innovative delivery systems that increase their immunogenicity. The use of nanotechnology in vaccinology is providing the opportunity to contrast these difficulties and develop effective vaccines. Particularly, nanoparticles used as vehicles of vaccine components, are able to increase the host's immune responses and, due to their size, to reach specific cellular districts. To date, a certain number of nanovaccines has been approved for human health and many are studied in clinical or pre-clinical trials. There are several types of nanoparticles considered as possible delivers of vaccine antigens. These nanoparticles-based synthetic delivery systems, in the size range of 20-200 nm, protect antigen from degradation, enhance its presentation and facilitate its uptake by professional antigen-presenting cells. Virus-like particles, self-assembled proteins, micelles, liposomes, inorganic nanoparticles, and polymers are the most studied of these systems. In this review, we provide a general overview of different types, methods of synthesis, characterizations, properties and applications of nanoparticles in vaccine production.

A study about mechanisms of des-gamma-carboxy prothrombin's production in hepatocellular carcinoma.

AIM: Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin, increased in serum of patients with hepatocellular carcinoma (HCC) as result of an acquired defect of post-translational carboxylation of prothrombin's precursor. It is unclear if the reduced activity of gamma-carboxylase is secondary to vitamin K deficiency or to an altered gene encoding this enzyme. The aim of this study was to evaluate the effect of vitamin K administration on DCP and alpha-fetoprotein (AFP) levels, to identify a relationship between vitamin K and DCP serum levels and to investigate mechanisms of serum elevation of DCP levels. METHODS: The authors determined DCP and AFP serum levels and vitamin K concentration in 64 cirrhotics with HCC and in 60 cirrhotic subjects without HCC. In HCC subjects DCP and AFP levels were measured before and after vitamin K administration. A t-test for unpaired data was applied (P values <0.05 statistically significant). RESULTS: Only HCC patients had detectable levels of DCP and significant AFP levels. Administration of vitamin K reduced DCP but not AFP levels in HCC patients. No correlation was observed between vitamin K concentration and DCP levels: vitamin K concentration was similar both in HCC patients and in control group without HCC; HCC patients had the same vitamin K concentration regardless of elevated o reduced DCP levels after vitamin K administration. CONCLUSION: DCP detectable serum levels are the result not only of vitamin K deficiency or selective defects of carboxylase, because probably alterations of membrane receptors or cytoplasmatic transfers, that are necessary for the function of vitamin K, are involved.

Serum interleukin-6 levels are increased in HIV-infected patients that develop autoimmune disease during long-term follow-up.

BACKGROUND: Elevated IL-6 levels have been associated with both autoimmune diseases and treated HIV-seropositive (HIV+) subjects. However, few data on classic and trans-signaling IL-6 in autoimmune thyroid diseases and HIV+ subjects developing autoimmune disorders are currently available. MATERIALS AND METHODS: A total of 102 patients were included in the study. They were subdivided into two groups. Group A consisted in 51 HIV+ patients, who were followed-up for a period of five years in search of possible occurrence of autoimmune diseases. Ten of them, treated with antiretroviral therapy (ART), developed an autoimmune disorder, namely Hashimoto's thyroiditis, and psoriasis. Group B consisted in 51 patients affected by Hashimoto's thyroiditis (HT). Serum levels of the free form of IL-6 were analyzed by ELISA in all patients and for HIV+ patients at the beginning of the follow-up, before initiation of ART. RESULTS: Mean serum levels of IL-6 were similar in Group A and in Group B. In Group B, IL-6 levels showed a 5.8% increase compared with assay minimum detectable dose corresponding to 1% of full serum IL-6 level. However, serum levels of free IL-6 were increased in those HIV+ patients who developed autoimmune disorders (5.8±2.8pg/ml) and in these patients, the highest levels of free IL-6 correlated with age and CD4 cellular counts. CONCLUSIONS: The present study indicates a correlation between serum free IL-6 levels and the occurrence of autoimmune disease in HIV+ population, treated with ART during a long-term follow-up. The increased levels of serum free IL-6 were observed before ART treatment was initiated, indicating that IL-6 measurement in such patients may represent an early predictor of development of autoimmune disease.

Expression of hepatocyte growth factor in Hashimoto's thyroiditis with nodular lesions.

Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease frequently associated with hyperplastic nodules (HN)s. Hepatocyte growth factor (HGF) is expressed in benign thyroid nodules and over-expressed in malignant thyroid nodules, particularly in papillary thyroid carcinomas. To elucidate the role of HGF in the development of HNs in association with HT we evaluated, by immunohistochemistry, the expression of HGF in both nodular and extranodular tissues, obtained from 30 HTs and 15 goiter samples. Six normal thyroid glands were used as controls. All normal control tissue samples exhibited no evidence of HGF immunoreaction. HNs showed weak to moderate HGF immunoreaction, which was located exclusively in the cytoplasm of stromal cells (fibroblasts and endothelial cells). However, the percentage of positive cases was higher in HNs arisen in the context of HT, compared to HNs not associated with HT (30/30 or 100% vs 4/15 or 40%; p<0.001). HGF immunoreactivity was also detected in all extranodular tissues from HT specimens (30/30 or 100%), but we found some significant differences. In fact, while in HNs observed in the context of HT lesions HGF was expressed only in stromal cells, in the extranodular tissues from the same thyroid gland affected by HT it was also detected in the cytoplasm of the epithelial follicular cells. Furthermore, HTs showed a much higher HGF staining grade in the extranodular tissue compared to HNs. Finally, a clear positive correlation was observed in HT between the proportion of HGF expressing follicular cells and the grade of lymphoid aggregates of the thyroid gland. In conclusion, HGF is much more frequently and highly expressed in thyroid tissue with HT, compared to goiter. In HT glands HGF can be detected in both follicular thyroid cells and stromal cells, while in HNs, either from goiters or associated with HT, its expression is restricted only to the stromal cells. These data indicate that HGF may play a role in cell proliferation processes occurring in thyroid glands affected by HT, probably under the regulation of the lymphoid infiltrate.

[Hepatic hydatidosis: old and actual therapeutic strategies]. / L'idatidosi epatica: pregresse e attuali strategie terapeutiche.

The authors, reporting on their experience, confirm as the incidence of the hepatic hydatidosis and the complications related to this pathology today are very meaningful. They specify that the objectives to be pursued are: elimination of the parasite, prevention or treatment of the complications, prevention of the development of a new infestation. They dwell therefore upon the various techniques, both conservative and radical, that marked the history of the hepatic hydatidosis surgery, and they conclude affirming that the procedures of eradication of the parasite and the pericystectomy, in particular in laparotomic way, also represents the ideal treatment in consideration of the a little encouraging results of the medical therapy.

[Our experience in the surgical treatment of mesenchymal gastric tumors]. / La nostra esperienza nel trattamento chirurgico dei tumori mesenchimali dello stomaco.

A retrospective review on 22 patients with gastric mesenchymal tumors, who underwent surgical treatment in the period 1974-2003, is presented. The aim of the study was to review our cases in the light of the new pathologic and immunohistochemical definitions and to analyse the value of clinical signs, diagnostic methods and principles of surgical technique. The Authors conclude that no specific clinical signs have been detected. Endoscopy plays a very important diagnostic role and CT-scan is the most sensible technique in the evaluation of location, size, invasion of adjacent organs and metastasis. The aim of treatment must be the complete resection of the tumor and the prognostic prediction on the basis of histologic findings is quite difficult.

Expression of P53 and isoforms in bening and malignant lesions of the head and neck.

BACKGROUND: P53, a crucial suppressor of tumor formation, generates multiple isoforms, whose role in disease is still being defined. METHODS: By immunohistochemistry, we studied the expression of P53 protein and relative isoforms in benign papillomas (PA, n=9), inverted papilloma (IPA, n=10) and squamous cell carcinomas (SCC, n=21). RESULTS: In all lesions, P53 isoforms were significantly more expressed than P53. Immunoexpression of P53 matched with P53 isoforms in IPA as well as in SCC. Simultaneous immunoexpression of P53 and related isoforms was double in SCC compared to IPA (10% vs 24%), while expression of P53 isoforms was strongly reduced (70% vs 43%). IPA showed the highest percentage of both reactive cases and immunostained cells expressing P53 isoforms. CONCLUSIONS: We found the higher expression of P53 isoforms in IPA and SCC compared to PA, suggesting their role in local aggressiveness and malignant proliferation in head-neck lesions.

Immunoexpression of CD30 and CD30 ligand in deciduas from spontaneous abortions.

In the present study, using immunohistochemistry, we studied the expression of CD30 and CD30-L in 35 deciduas obtained from women following elective abortion during normal physiological gestation and in 60 deciduas obtained from women after spontaneous abortion with or without signs of inflammation. The main difference was noticed in the first trimester of gestation in which was found a decrease in CD30/CD30-L-positive decidual glandular and stromal cells in a greater number of cases of spontaneous abortions with respect to cases of physiological pregnancies (70% vs 50%, p<0.05). In addition, deciduas from spontaneous abortions with inflammation and without inflammation reacted similarly. The reduced expression of CD30 and CD30-L and their cellular pattern detected in the deciduas from spontaneous abortions suggest that the CD30/CD30-L system is crucial for preventing abortions in the first trimester. Furthermore, the distinctive expression of CD30/CD30-L in deciduas from physiological pregnancies may indicate that the CD30/CD30-L system exerts its main role in the first trimester.

Nosocomial infections in colo-rectal surgery of the old patient.

Every surgical act, especially in geriatric age, can be a relevant moment in the onset of nosocomial infections. This has a peculiar aspect in patient who undergo colo-rectal surgery, both in election and especially in emergency, in which the simple opening of intestines always involves a minimal contamination. In order to reduce the incidence of infections, and therefore the septic complications of this surgery, it is necessary to pay attention to the preparation of the surgical equipe, of the operating room, of the surgical instruments and, in election, to the careful preparation of the patient through a careful evaluation of the possible bio-umoral alterations, in order to correct them. The results of our experience allow us to say that the prevention of post-operatory sepsis find its main moment in the careful evaluation and eventual correction of the nutritional status, in the stimulation of the immune system, in the antibiotic prophylaxis both parenteral and topical, and, last but not least, in a correct surgical technique. All this is particularly important for patients affected by colo-rectal neoplastic and inflammatory diseases, for which the intestinal bacteria, more virulent in weak and fragile patients, often represent the source of contamination that can start a sepsis and then assume an important part in determining the final result of surgery.

Loss of heterozygosity of the long arm of chromosome 7 in follicular and anaplastic thyroid cancer, but not in papillary thyroid cancer.

Papillary thyroid cancer (PTC), but neither the follicular nor the anaplastic histotype [follicular thyroid cancer (FTC), anaplastic thyroid cancer (ATC)], overexpresses simultaneously the protooncogene HGF (hepatocyte growth factor) and its receptor HGF-R (or c-met). Because 1) HGF and c-met map to chromosome 7q21 and 7q31, respectively, 2) FTC loses genetic material at multiple loci with a frequency much higher than PTC, and 3) loss of heterozygosity (LOH) on 7q has been previously found in various tumors, we tested the hypothesis that both FTC and ATC, but not PTC, could harbor LOH in segments of 7q encompassing the loci for HGF and c-met. We screened 6 normal thyroids, 10 colloid nodules, 10 follicular hyperplasias, 10 oncocytic adenomas, 10 follicular adenomas (FA), 10 FTC, 6 ATC, 12 PTC using two microsatellite markers for HGF, and two for c-met. LOH for all 4 markers was found in 100% of FTC, 100% of ATC, and (for only 1 or 2 markers) in 10-29% of FA. This is the first demonstration of an LOH that separates both FTC and ATC from PTC, in the best possible manner: 100% vs. 0%. Clearly, each of the two segments we have probed contains at least one tumor suppressor gene, whose inactivation is crucial for the establishment of the FTC (and ATC) phenotype. This loss of genetic material explains why FTC and ATC, but not PTC, fail to express both HGF and c-met. Our findings may also have immediate diagnostic application, in the context of assisting pathologists in the often difficult task of distinguishing FA from FTC.

Expression of Agrobacterium rhizogenes rolB gene fusions in Escherichia coli: production of antibodies against the RolB protein.

Expression of the rolB gene of Agrobacterium rhizogenes TL-DNA is sufficient to trigger root differentiation in transformed plant cells. To investigate the role of RolB in differentiation, a large portion of rolB, comprising about 90% of its C-terminal coding sequence, was cloned into vectors pEX34 and pEA305 in frame with the truncated N termini of the pL-MS2 phage DNA polymerase and, respectively, the ptac-c Its phage lambda repressor gene. Hybrid proteins were expressed from both fusions and the one from pMTBEX1 was utilized to raise antibodies. These antibodies specifically recognize the RolB moiety in both pL-MS2-rolB and ptac-cI-rolB fusions. Unfused, complete RolB protein was obtained by in vitro translation in a rabbit reticulocyte system of a transcript obtained by in vitro transcription of rolB. RolB protein is specifically immunoprecipitated by the antibodies raised against the hybrid protein MS2-RolB.

Immunoexpression of the hepatocyte growth factor (HGF), HGF-receptor (c-met) and STAT3 on placental tissues from malformed fetuses.

To characterize the possible relationship between the expression of the HGF/HGF-R system with transcription factor STAT3, responsible for morphogenetic response of HGF stimulation, and the embryonic development alterations, we investigated, by immunohistochemistry, the expression of HGF, c-met and STAT3 in 9 placentas from malformed fetuses and 9 control placentas from non-malformed fetuses. The major and distinct patterns of expression characterizing the placentas from malformed fetuses were a higher percentage mean of stromal cells stained for HGF, c-met and STAT3 antibodies (60%, 66% and 54%, respectively on fibroblast cells and 44%, 57% and 42%, respectively on myofibroblast cells) and a lower percentage mean of cytotrophoblast cells stained for the same antibodies (2%, 2% and 1%, respectively), than in control placentas. In fact, in this latter group, the stromal fibroblast cells were stained in a percentage mean of 27%, 22% and 7%, respectively; the stromal myofibroblast cells in a percentage mean of 5%, 6% and 2%, respectively and the cytotrophoblast cells in a percentage mean of 25%, 34% and 18%, respectively. The expression of each antibody on stromal cells in both groups suggests an alternative role of the HGF/HGF-R system activating the via STAT3 transdution and operating on placental tissues, overall in organogenesis alteration conditions. This immunohistochemical approach could be used in the diagnostic practice of pathologists on chorionic villi biopsy when genetic alterations are absent and ultrasound aspects are doubtful for malformations.

Distinctive expression of STAT3 in papillary thyroid carcinomas and a subset of follicular adenomas.

Hepatocyte growth factor (HGF), HGF receptor (c-met) and the interleukin 6 (IL-6) are expressed in thyroid nodules. In extra-thyroidal tissues, the HGF/c-met and IL-6/IL-6 receptor (IL-6R) systems activate STAT3, a member of the signal transducers and activators of transcription (STATs) family. To evaluate whether either system utilizes STAT3 in thyroid nodules, we examined the immunohistochemical expression of HGF, c-met, IL-6, IL-6R, STAT3 in 6 normal thyroids and in 68 thyroid nodules. STAT3 expression was observed in 12/12 (100%) papillary thyroid carcinomas (PTC) but in none of the follicular tumors. Among benign thyroid nodules, only 2/10 (20%) follicular adenomas (FA) were STAT3+. All these 14 STAT3+ cases expressed both HGF and c-met, but only 5 PTC co-expressed IL-6 and IL-6R and the 2 FA were IL-6+ but IL-6R-. The remaining 8 FA were all HGF/c-met-, but IL-6+; of these 8, only 2 were also IL-6R+. In conclusion, in thyroid nodules STAT3 is expressed only in PTC and a number of FA. Since these cases are consistently HGF+/c-met+ and only one-third of them co-express IL-6/IL-6R, STAT3 expression correlates with the HGF/c-met expression, not with the IL-6/IL-6R expression. The 100% rate of expression of the HGF/c-met/STAT3 signaling in PTC could be relevant for the establishment of the papillary phenotype. Because of the communeness of a HGF/c-met/STAT3 pattern between all PTC and a subset of FA, we speculate that a fraction of FA may progress to PTC.

Expression of the hepatocyte growth factor and c-met in normal thyroid, non-neoplastic, and neoplastic nodules.

We have examined the coexpression of hepatocyte growth factor (HGF) and its receptor (HGF-R or c-met) in an archival series of 63 paraffin-embedded thyroid specimens plus one lymph node metastasis. By immunocytochemistry, we found undetectable expression of both the ligand and the receptor in 10 normal thyroids and 9 nonpapillary malignant nodules [5 follicular carcinomas, 1 poorly differentiated (insular) carcinoma, 3 undifferentiated (anaplastic) carcinomas]. Of 10 non-neoplastic nodules (colloid nodules) and 17 benign neoplastic nodules, 3 of 10 colloid nodules, 2 of 10 follicular adenomas, and 2 of 7 oncocytic adenomas showed a weak but distinct staining (1+ score in a scale from 0 to 4+) of both HGF and c-met in a modest proportion of cells (1% to 3%). In these 7 cases, expression of HGF was always stromal and expression of c-met limited to the membrane of the follicular cells. Of 3 malignant nodules derived from aberrant growth of the parafollicular C cells (medullary thyroid cancer or MTC), 2 were positive (6% of cells). In these 2 cases, the expression of HGF (3+) was not stromal, but in both the membrane and cytoplasm of the parafollicular cells, while that of c-met (3+) was restricted to the membrane. In contrast to all of the above, of 14 papillary carcinomas (PTC) encompassing 5 histological variants (conventional; follicular; oncocytic; with foci of solid growth; diffuse sclerosing) plus 1 neck lymph node metastasis of 1 conventional PTC, 12 (86%) expressed HGF, and 13 (93%) expressed c-met. With the exception of 2 negative cases, HGF was detected in 15% to 46% of the cells. The highest percentage (46%) pertained to conventional PTC cases with abundant peritumoral lymphocyte infiltration, indicating that some lymphokine(s) may recruit PTC cells for HGF expression in a paracrine fashion. With the exception of one negative case, c-met was found in 43% to 80% of the cells, both at levels from intense (3+) to very intense (4+). The immunostaining for HGF was stromal in 25%, membranous in 8%, cytoplasmic in 8%, and both membranous and cytoplasmic in 59% of the PTC-positive cases. The immunostaining for c-met was membranous in 43% and both membranous and cytoplasmic in 57% of the PTC-positive cases. In the lymph node metastasis and in the diffuse sclerosing variant of PTC (the most aggressive variant), the coexpression of HGF/c-met was lost, in that only c-met was expressed on membranes in both cases. We conclude that the HGF/c-met system is activated (by overexpression of both components) in the vast majority of PTC. In most PTC the interaction of HGF and its receptor (c-met) is autocrine, not paracrine.

Expression of CD30 ligand and CD30 receptor in normal thyroid and benign and malignant thyroid nodules.

Because the CD30 ligand (CD30L)/CD30 receptor (CD30) system is expressed in certain malignancies, but has not been studied in thyroid nodules, we investigated its immunohistochemical expression in 6 normal thyroids (NT) and 131 thyroid nodules: 28 colloid nodules (CN), 45 adenomas (15 oncocytic [OA], 30 follicular [FA]) and 58 carcinomas (15 follicular [FTC], 1 insular [ITC], 6 anaplastic [ATC], 30 papillary [PTC], and 6 medullary [MTC]). NT and CN expressed neither CD30L nor CD30 (CD30L-/CD30-). Forty percent of OA and 20% of FA showed epithelial coexpression of CD30L and CD30, and interstitial expression of CD30L, which was also observed in the surrounding normal tissue. Within malignancies, epithelial coexpression of CD30L and CD30 was observed in 7% of FTC, 33% of ATC, 67% of PTC, and 67% of MTC. Only PTC and MTC showed epithelial expression of CD30L in the perinodular tissue with similar frequency (80% PTC, 75% MTC). PTC and MTC had the highest proportion of CD30L+ or CD30+ cells, and together with OA, a thus far unreported nuclear location of CD30L. In PTC, the proportion of CD30L+ cells and the prevalence of nuclear location of CD30L correlated inversely and directly, respectively, with aggressiveness. In conclusion, CD30L/CD30 signaling is activated only past the colloid nodule stage, most frequently in an autocrine fashion.