Comparison of [¹¹¹In]pentetreotide-SPECT and [¹8F]FDOPA-PET in the localization of extra-adrenal paragangliomas: the case for a patient-tailored use of nuclear imaging modalities.

AIMS AND METHODS: The aim of this prospective study was to compare the diagnostic value of [¹8F]FDOPA-PET and [¹¹¹In]pentetreotide-SPECT somatostatin receptor scintigraphy (SRS) in patients with nonmetastatic extra-adrenal paragangliomas (PGLs). Twenty-five consecutive unrelated patients who were known or suspected of having nonmetastatic extra-adrenal PGLs were prospectively evaluated with SRS and [¹8F]FDOPA-PET. ¹³¹I-MIBG and [¹8F]FDG-PET were added to the work-up in patients with a personal or familial history of PGL, predisposing mutations, abdominal PGLs, metanephrine hypersecretion and abdominal foci on SRS and/or [¹8F]FDOPA-PET. RESULTS: SRS correctly detected 23/45 lesions of which 20 were head or neck lesions (H&N) and 3 were abdominal lesions. [¹8F]FDOPA-PET detected significantly more lesions than SRS (39/45, P < 0·001). Both SRS and ¹8F-DOPA-PET detected significantly more H&N than abdominal lesions (66·7% vs 20%, P = 0·003 and 96·7% vs 67%, P = 0·012, respectively). In two patients with the succinate dehydrogenase D (SDHD) mutation, [¹8F]FDOPA-PET missed five abdominal PGLs which were detected by the combination of SRS, [¹³¹I]MIBG and [¹8F]FDG-PET. A lesion-based analysis using a forward stepwise logistic regression model demonstrates that size ≤ 10 mm (P = 0·002) and abdominal lesions (P = 0·031) were independently associated with "[¹8F]FDOPA-PET diagnosis only". In turn, a previous history of surgery and/or the presence of germline mutation was associated with lower lesion size (P = 0·001). CONCLUSIONS: The sensitivity of SRS for localizing parasympathetic PGLs is lower than originally reported, and [¹8F]FDOPA-PET is better than SRS for localizing small lesions. SRS should be replaced by [¹8F]FDOPA-PET as the first-line imaging procedure in H&N PGL, especially in patients at risk of multifocal disease (predisposing mutations and or previous history of surgery).

Mild hypercalcitoninaemia and sporadic thyroid disease.

BACKGROUND: Not operating on patients with mild hypercalcitoninaemia (MHCT) and sporadic thyroid disease carries the risk of omitting curative surgery for medullary thyroid cancer, but systematic surgery would result in unnecessary treatment of benign pathology. This study reviewed the management of MCHT and non-hereditary thyroid disease in one centre. METHODS: MCHT was defined as an increase in basal and stimulated calcitonin levels not exceeding 30 and 200 pg/ml respectively. Over 15 years, 125 patients who presented with MCHT and sporadic thyroid disease were followed. Surgery was indicated only if there were local pressure symptoms or suspicious histomorphological changes in solitary nodules. RESULTS: Fifty-five patients underwent total thyroidectomy and 18 unilateral total lobectomy. Histological examination revealed medullary microcarcinoma in six patients (two women and four men). C-cell hyperplasia was found in 54 patients (74 per cent) and 13 (18 per cent) harboured no C-cell pathology. Calcitonin levels stabilized after lobectomy and became undetectable following thyroidectomy. They normalized during follow-up in a third of patients who did not have surgery. CONCLUSION: Not all patients with MHCT and sporadic thyroid disease require surgery.

Tumor protein p53-induced nuclear protein (TP53INP1) expression in medullary thyroid carcinoma: a molecular guide to the optimal extent of surgery?

BACKGROUND: Medullary thyroid cancer (MTC) is characterized by early regional lymph node metastasis, the presence of which represents a critical obstacle to cure. At present no molecular markers have been successfully integrated into the clinical care of sporadic MTC. The present study was designed to evaluate TP53INP1 expression in MTC and to assess its ability to guide the surgeon to the optimal extent of surgery performed with curative intent. METHODS: Thirty-eight patients with sporadic MTC were evaluated. TP53INP1 immunoexpression was studied on embedded paraffin material and on cytological smears. RESULTS: TP53INP1 was expressed in normal C cells, in C-cell hyperplasia, and in 57.9% of MTC. It was possible to identify two groups of MTC according to the proportion of TP53INP1 expressing tumor cells: group 1 from 0% to <50% and group 2 from 50% to 100% of positive cells. Patients with a decreased expression of TP53INP1 (group 1) had a lower rate of nodal metastasis (18.8% versus 63.4% in group 2; P = 0.009), with only minimal lymph node involvement per N1 patient (2.7% of positive lymph nodes versus 22.9%; P < 0.001) and better outcomes (100% of biochemical cure versus 55.5%; P < 0.001). Patients with distant metastases were only observed in group 2. Cytological samples exhibit similar results to their embedded counterparts. CONCLUSIONS: TP53INP1 immunoexpression appears to be a clinical predictor of lymph node metastasis in MTC. The evaluation of TP53INP1 expression may guide the extent of lymph node dissection in the clinically node-negative neck. These findings require prospective validation.

Quality of life changes and clinical outcomes in thyroid cancer patients undergoing radioiodine remnant ablation (RRA) with recombinant human TSH (rhTSH): a randomized controlled study.

BACKGROUND: Recombinant human TSH (rhTSH) has become the modality of choice for radioiodine remnant ablation (RRA) in low-risk thyroid cancer patients. AIMS AND METHODS: The aims of the present prospective randomized study were to evaluate the impact of TSH stimulation procedure (hypothyroidism vs. rhTSH) on quality of life (QoL) of thyroid cancer patients undergoing RRA and to evaluate efficacy of both procedures. L-T4 was initiated in both groups after thyroidectomy. After randomization, L-T4 was discontinued in hypothyroid (hypo) group and continued in rhTSH group. A measure of 3.7 GBq of radioiodine was given to both groups. The functional assessment of chronic illness therapy-fatigue (FACIT-F) was administered from the early postoperative period to 9 months. Socio-demographic parameters, anxiety and depression scales were also evaluated (CES-D, BDI and Spielberger state-trait questionnaires). At 9 months, patients underwent an rhTSH stimulation test, diagnostic (131)I whole body scan (dxWBS) and neck ultrasonography. RESULTS: A total of 74 patients were enrolled for the study. There was a significant decrease in QoL from baseline (t0) to t1 (RRA period) in the hypothyroid group with significant differences in FACIT-F TOI (P < 10(-3)), FACT-G total score (P = 0.005) and FACIT-F total score (P = 0.003). By contrast, QoL was preserved in the rhTSH group. In the multivariate analysis, FACIT-TOI changes were only affected by the modality of TSH stimulation performed for RRA. From 3 to 9 months, changes of QoL scales and subscales were no longer statistically different in both groups of patients. Based on serum rhTSH-stimulated Tg alone (Tg < 0.8 microg/l, BRAHMS Tg Kryptor), no difference in ablation success was observed between rhTSH and hypothyroidism groups, 91.7% and 97.1%, respectively. A higher rate of persistent thyroid remnants was observed in the rhTSH arm, although in most cases uptake was < 0.1% and of no clinical significance. CONCLUSIONS: rhTSH preserves QoL of patients undergoing RRA with similar rates of ablation success compared to hypothyrodism. However, there is a wide heterogeneity in the clinical impact of hypothyroidism.

The role of 18F-FDOPA and 18F-FDG-PET in the management of malignant and multifocal phaeochromocytomas.

BACKGROUND: (18)F-DOPA has emerged as a promising tool in the localization of chromaffin-tissue-derived tumours. Interestingly, phaeochromocytomas (PHEO) are also FDG avid. AIM AND METHODS: The aim of this study was to retrospectively evaluate the results of (18)F-FDOPA and/or (18)F-FDG-PET in patients with PHEO and paragangliomas (PGLs) and to compare the outcome of this approach with the traditional therapeutic work-up. Nine patients with non-MEN2 related PHEO or PGL were evaluated. At the time of the PET studies, the patients were classified into three groups based on their clinical history, conventional and SPECT imaging. The groups were malignant disease (n = 5, 1 VHL), apparently unique tumour site in patients with previous surgery (n = 1, SDHB) and multifocal tumours (n = 3, 1 VHL, 1 SDHD). (18)F-FDOPA and (18)F-FDG-PET PET/CT were then performed in all patients. RESULTS: PET successfully identified additional tumour sites in five out of five patients with metastatic disease that had not been identified with SPECT + CI. Whilst tumour tracer uptake varied between patients it exhibited a consistently favourable residence time for delayed acquisitions. (18)F-FDOPA uptake (SUVmax) was superior to (18)F-FDG uptake in cases of neck PGL (three patients, four tumours). If only metastatic forms and abdominal PGLs were considered, (18)F-FDG provided additional information in three cases (two metastatic forms, one multifocal disease with SDHD mutation) compared to (18)F-FDOPA. CONCLUSIONS: Our results suggest that tumour staging can be improved by combining (18)F-FDOPA and (18)F-FDG in the preoperative work-up of patients with abdominal and malignant PHEOs. (18)F-FDOPA is also an effective localization tool for neck PGLs. MIBG however, still has a role in these patients as MIBG and FDOPA images did not completely overlap.

Desmoplasia in medullary thyroid carcinoma: a reliable indicator of metastatic potential.

AIMS: To evaluate the reliability of desmoplasia as a reproducible morphological parameter indicating the metastatic potential of medullary thyroid carcinoma (MTC). METHODS AND RESULTS: One hundred and twenty cases of MTC of the Medical University of Vienna, Austria and 76 cases from the School of Medicine of Marseille, France were analysed for the presence of desmoplastic stroma reaction by four endocrine pathologists. Intra- and interobserver concordance was assessed. The Austrian cases were also analysed for various morphological parameters. Intra- and interobserver concordance were highly significant with a kappa value of 0.883 for intra-observer reliability and 0.837, 0.79 and 0.758, respectively, when pathologists N.N., C.D.M. and K.W.S. reviewed the Austrian cases. The cases from France were reviewed by C.D.M. and K.K. with a kappa value of 0.759. None of the cases that were categorized as desmoplasia negative by any of the investigators showed lymph node metastasis. No other distinct morphological characteristics could be assigned to the MTCs without desmoplasia. CONCLUSIONS: Our data indicate desmoplasia to be a reliable and highly reproducible parameter with regard to lymph node metastatic potential.

Does 18F-FDG PET/CT add diagnostic accuracy in incidentally identified non-secreting adrenal tumours?

PURPOSE: The widespread use of high-resolution cross-sectional imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) for the investigation of the abdomen is associated with an increasing detection of incidental adrenal masses. We evaluated the ability of (18)F-fluorodeoxyglucose positron emission tomography to distinguish benign from malignant adrenal masses when CT or MRI results had been inconclusive. METHODS: We included only patients with no evidence of hormonal hypersecretion and no personal history of cancer or in whom previously diagnosed cancer was in prolonged remission. PET/CT scans were acquired after 90 min (mean, range 60-140 min) after FDG injection. The visual interpretation, maximum standardised uptake values (SUVmax) and adrenal compared to liver uptake ratio were correlated with the final histological diagnosis or clinico-radiological follow-up when surgery had not been performed. RESULTS: Thirty-seven patients with 41 adrenal masses were prospectively evaluated. The final diagnosis was 12 malignant, 17 benign tumours, and 12 tumours classified as benign on follow-up. The visual interpretation was more accurate than SUVmax alone, tumour diameter or unenhanced density, with a sensitivity of 100% (12/12), a specificity of 86% (25/29) and a negative predictive value of 100% (25/25). The use of 1.8 as the threshold for tumour/liver SUVmax ratio, retrospectively established, demonstrated 100% sensitivity and specificity. CONCLUSION: FDG PET/CT accurately characterises adrenal tumours, with an excellent sensitivity and negative predictive values. Thus, a negative PET may predict a benign tumour that would potentially prevent the need for surgery of adrenal tumours with inconclusive conventional imaging.

Aggressive multimodal therapy of sporadic malignant insulinoma can improve survival: a retrospective 35-year study of 12 patients.

AIM: Sporadic malignant insulinoma (SMI) is a rare disease, and the consequent paucity of data in the literature and the development of aggressive treatments for liver metastases have led us to retrospectively analyze a series of 12 cases of SMI. METHODS: Every patient presenting with SMI, according to the WHO 2004 histopathology criteria, between 1970 and June 2005 in Marseille was included in the study. Patients with multiple endocrine neoplasia type 1 (MEN-1) and tumours of uncertain malignant potential were excluded. RESULTS: The ratio of male/female was 4/8, and mean age at diagnosis was 52.5 years. A 48-h fasting test in 10 patients was conclusive in nine, after a mean duration of 12 h 45 min. SMI size ranged from 7-120 mm (mean 30.3mm). Six patients had liver metastases and one had isolated lymph-node invasion. Surgery was performed in 12 patients. Five persisting diseases (mean follow-up of 1.8 years) required other treatments (chemoembolization, radiofrequency thermoablation [RFTA], liver transplantation); one patient relapsed 8.5 years after surgery; six were still in complete remission (mean follow-up of 5.8 years), and one patient had died by the time of the 24-month follow-up. CONCLUSION: Aggressive sequential multimodal therapy can prolong the survival of patients with SMI even in the presence of liver metastases.

Expression of tpo mRNA in thyroid tumors: quantitative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes.

Immunocytochemistry (ICC) of thyroid peroxidase (TPO) using the monoclonal antibody MoAb47 has been used as malignancy marker on thyroid fine needle aspiration. However, little is known about the fate of TPO in thyroid carcinoma. We performed a qualitative PCR (Q-PCR) analysis to measure the expression of variants of tpo mRNA in 13 normal tissue samples, 30 benign tumors (BT), 21 follicular carcinomas (FC), 20 classical papillary carcinomas (PCc), 12 follicular variants of papillary carcinomas (PCfv) and nine oncocytic carcinomas (OC). We also studied mutations involving the ras, Braf, ret or pax8 genes. Results of Q-PCR were closely correlated with those of ICC (P < 0.0001; R = 0.59) and showed that overall tpo expression was lower in all carcinomas than in normal and BT (P < 0.05). The ratio tpo2 or tpo3 to tpo1 was inversed in follicular tumors. Genetic mutations were observed in 90% of PCc, 61.9% of FC, 41.7% of PCfv, 0% of OC and 10% in BT. pax8-ppar gamma1 rearrangement was correlated with qualitative changes in tpo mRNA (P < 0.01). These results confirmed the decrease of TPO expression in 97% of thyroid carcinomas regardless of histological type and the overexpression of shorter splice variants in follicular tumors. Both reduction in quantity of TPO and impairment of its maturation process could account for the atypical immunohistochemical reaction of MoAb47 with TPO.

[Abrikossoff tumor of the proximal esophagus misdiagnosed as a thyroid nodule]. / Tumeur d'Abrikossoff de l'oesophage cervical: une cause rare de faux nodule thyroïdien.

The diagnosis of thyroid nodules is straightforward and rarely mistaken. We present a case of a paraesophageal granular cell tumor, discovered incidentally during surgery for what it was diagnosed as a suspicious thyroid nodule by ultrasound and FNA. Complete resection was achieved without disruption of the esophageal mucosa. A terminal branch of the recurrent laryngeal nerve had to be resected en bloc with the tumor. Morphological and immunohistochemical diagnosis was established postoperatively. A review of the literature is presented.

ret/PTC1 and ret/PTC3 in thyroid tumors from Chernobyl liquidators: comparison with sporadic tumors from Ukrainian and French patients.

Like children exposed to Chernobyl fallout, the workers who cleaned up after the accident, also known as liquidators, have exhibited an increased incidence of thyroid cancer. A high prevalence of ret/PTC3 rearrangement has been found in pediatric post-Chernobyl thyroid tumors, but this feature has not been investigated in liquidator thyroid tumors. In this study we analyzed the prevalence of ret/PTC1 and ret/PTC3 in thyroid tumors from 21 liquidators, 31 nonirradiated adult Ukrainian patients, and 34 nonirradiated adult French patients. ret rearrangements in carcinomas were found in 83.3% of liquidators, 64.7% of Ukrainian patients, and 42.9% of French patients. The prevalence of ret/PTC1 was statistically similar in the three groups. The prevalence of ret/PTC3 was significantly higher in liquidators than in French patients (P = 0.03) but it was also high in nonirradiated Ukrainian patients who exhibited values intermediate between liquidators and French patients. In adenomas the prevalence of rearrangement was significantly higher in all Ukrainians than in French patients (P = 0.004). Like children exposed to Chernobyl fallout, liquidators showed a high prevalence of ret/PTC3. This finding suggests that irradiation had the same effect regardless of age. However, given the high rate of ret/PTC3 in nonirradiated adult Ukrainians, the possibility of genetic susceptibility or low-level exposure to radiation in that group cannot be excluded.

Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer.

INTRODUCTION: Akt activation is involved in the pathogenesis of inherited thyroid cancer in Cowden's syndrome and in sporadic thyroid cancers. In cell culture, Akt regulates thyroid cell growth and survival; but recent data suggest that Akt also regulates cell motility in non-thyroid cell lines. We therefore sought to evaluate the role of Akt in thyroid cancer progression. METHODS: We evaluated 46 thyroid cancer, 20 thyroid follicular adenoma, and adjacent normal tissues samples by immunohistochemistry for activated Akt (pAkt), Akt 1, 2, and 3, and p27 expression. Immunoblots were performed in 14 samples. RESULTS: Akt activation was identified in 10/10 follicular cancers, 26/26 papillary cancers, and 2/10 follicular variant of papillary cancers, but in only 4/66 normal tissue samples and 2/10 typical benign follicular adenomas. Immunoactive pAkt was greatest in regions of capsular invasion; and was localised to the nucleus in follicular cancers and the cytoplasm in papillary cancers, except for invasive regions of papillary cancers where it localised to both compartments. Immunoactive Akt 1, but not Akt 2 or Akt 3, correlated with pAkt localisation, and nuclear pAkt was associated with cytoplasmic expression of p27. In vitro studies using human thyroid cancer cells demonstrated that nuclear translocation of Akt 1 and pAkt were associated with cytoplasmic p27 and cell invasion and migration. Cell migration and the localisation of Akt 1, pAkt, and p27 were inhibited by PI3 kinase, but not MEK inhibition. DISCUSSION: These data suggest an important role for nuclear activation of Akt 1 in thyroid cancer progression.

Specific pattern of RAS oncogene mutations in follicular thyroid tumors.

The prevalence of H-RAS, K-RAS, and N-RAS gene mutations in thyroid tumors according to malignancy and histology is controversial. Differences in methodology and histological classifications may explain discrepant results. To address this issue, we first performed a pooled analysis of 269 mutations garnered from 39 previous studies. Mutations proved significantly less frequent when detected with direct sequencing than without (12.3% vs. 17%). The rate of mutation involving N-RAS exon 1 (N1) and K-RAS exon 2 (K2) was less than 1%. Mutations of codon 61 of N-RAS (N2) were significantly more frequent in follicular tumors (19%) than in papillary cancers (5%) and significantly more frequent in malignant (25%) than in benign (14%) tumors. H-RAS mutations in codons 12/13 (H1) were found in 2-3% of all types of tumors, but H-RAS mutations in codon 61 (H2) were observed in only 1.4% of tumors, and almost all of them were malignant. K-RAS mutations in exon 1 were found more often in papillary than follicular cancers (2.7% vs. 1.6%) and were sometimes correlated with special epidemiological circumstances. The second part of this study involved analysis of 80 follicular tumors from patients living in Marseille (France) and Kiev (Ukraine). We used direct sequencing after PCR amplification of exons 1 and 2 of the three RAS genes. Common and atypical adenomas were separated using strict cytological criteria. Mutations of H1-RAS were found in 12.5% of common adenomas and one follicular carcinoma (2.9%). Mutations of N2-RAS occurred in 23.3% and 17.6% of atypical adenomas and follicular carcinomas, respectively. These results confirm the predominance of N2-RAS mutations in thyroid follicular tumors and their correlation with malignancy. They support the implication of N2-RAS mutations in the malignant progression of thyroid follicular tumors and the assumption that some atypical adenomas are precursors of follicular carcinomas.

Interest of routine measurement of serum calcitonin: study in a large series of thyroidectomized patients. The French Medullary Study Group.

The aim of our study was to assess the ability of routine calcitonin (CT) measurement to improve the preoperative diagnosis of medullary thyroid carcinoma (MTC) in nodular thyroid diseases. We systematically determined basal CT in 1167 patients before thyroid surgery and performed a pentagastrin (Pg) CT stimulation test in 121 of these patients whose basal CT level was normal. Sixteen MTC (1.37%) were found on histopathological examination of surgical specimens: 14 in the 34 patients (41.1%) with abnormal basal CT levels and 2 in the 1133 patients with normal basal CT levels (0.17%). An abnormal increase in Pg-stimulated CT was observed in 7 of the 121 patients tested and was related to microscopic MTC in 2 cases. Among 1167 thyroidectomized patients with nodular thyroid diseases, the prevalence of MTC was 1.37% and reached 41.1% when the basal CT level was abnormal (3% of the patients). CT evaluation detected MTC, whereas other procedures, such as fine needle aspiration cytology, failed, thus allowing early radical surgery. CT measurement should thus become a routine part of the diagnostic evaluation of nodular thyroid diseases.

Immunohistochemical study of 100 pancreatic tumors in 28 patients with multiple endocrine neoplasia, type I.

One hundred pancreatic tumors ranging in size from 0.3 to 7 cm were studied in 28 patients (17 male and 11 female patients; mean age 35 years) with multiple endocrine neoplasia, type I. An immunohistochemical study was performed on deparaffinized sections using the following antibodies: neuron-specific enolase, chromogranin A or synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), gastrin, adrenocorticotropic hormone, alpha-subunit of human chorionic gonadotropin, gonadotropin-releasing factor, serotonin, and calcitonin. Among the 100 tumors (all multiple), seven were unclassified, 10 were plurihormonal, and 83 produced a predominant hormonal secretion (with 50-90% of the same cell type), including 37 "A-cell tumors" (glucagon), 27 "B-cell tumors" (insulin), 11 PP-cell tumors, one G-cell tumor (gastrin) and one vasoactive intestinal peptide (VIP)-cell tumor. These multiple tumors had a different predominant hormonal secretion in the same patient in 23 of the 28 cases. There was a preferential association of A-cell tumor and B-cell tumor. Hyperplasia of the islets of Langerhans was not detected in adjacent pancreas. Nesidioblastosis was observed in 30% of cases.

Immunology of central nervous system tumors.

With progress in cellular immunology and the development of hybridoma technology, the idea of manipulating host-tumor immune interactions to improve the prognosis of brain tumors has aroused renewed interest. Although no brain tumor-specific antigens have been found, and in spite of the wide antigenic heterogeneity of brain tumor cells, some monoclonal antibodies possessing restricted specificity have been isolated and their potential clinical applications investigated. One of the most pronounced changes in the cellular immune responses of brain tumor patients is a profound depression of the T4-helper lymphocytes. Clinical and laboratory trials are under way to assess the ability of lymphokines, such as gamma-interferon or interleukin-2, to restore immunologic competence in these patients and potentiate a specific anti-tumor immunologic response. Recent work suggests that the endothelium-astrocyte complex may have a pivotal role in assisting the escape of brain tumors from the host's immunologic responses, since it is responsible for the intracerebral sequestration of antigens and local anti-tumor responses. In this review, the data on the antigenic properties of central nervous system tumors and the host's humoral and cellular immune responses to them are analyzed and potential immunologic therapies are discussed.

Role of the blood-brain barrier in the establishment of the immune response against polyoma virus-induced cerebral tumours in hamsters.

The existence of an immunological blood-brain barrier (BBB) is well established but its role in cerebral tumour immunology is less well defined. Attempting to clarify this problem we tested the graft rejection of polyoma virus-induced central nervous (CNS) tumours in hamsters after systemic or intracerebral immunization with polyoma virus. Animals were immunized by intracerebral or subcutaneous inoculations of polyoma virus before tumours were induced by intracerebral or intramuscular graft of polyoma-transformed hamster neuroglial cells. The growth of cerebral and muscular tumours was significantly inhibited in animals immunized subcutaneously. In animals immunized intracerebrally the inhibition of growth was highly significant for cerebral tumours and only very slight for intramuscular tumours. These results suggest that the blood-brain barrier allowed immunocompetent effector cells to penetrate inside the CNS but prevented the locally elicited cell-mediated immune response from diffusing outside the CNS. The ability of the brain to develop a local immune response and the partial lack of circulation of immunocompetent cells to cross the BBB could be mainly responsible for the special immune status of the CNS and may greatly interfere with the establishment of an efficient immune response toward brain tumours.

Immunoexpression of E-cadherin and beta-catenin correlates to survival of patients with hepatocellular carcinomas.

Expression of E-cadherin (E-cad) and -catenin ( -cat) was investigated immunohistologically in 91 cases of excised hepatocellular carcinomas. Immunodectection was altered in 56% of tumours for E-cad and in 30.8% for -cat. Downregulation of E-cad and -cat correlated with the size of tumours, and high nuclear grade, but only E-cad alteration correlated with the mitotic index. Alterations of E-cad and -cat expression correlated with survival. Although E-cad and -cat immunodetections were independent prognostic factors, their prognostic value was lower than that of current clinicopathological parameters.

Thyroid peroxidase immunodetection as a tool to assist diagnosis of thyroid nodules on fine-needle aspiration biopsy.

In a previous work we have reported the presence in 96.9% of malignant and 4.2% of benign thyroid tumors of an immunological abnormality of the enzyme thyroid peroxidase, impeding the fixation of the anti-thyroid peroxidase monoclonal antibody termed "MoAb47". The present study has been designed to establish the ability of thyroid peroxidase immunodetection to assist the diagnosis of malignancy in fine-needle aspiration of thyroid nodules. The fixation of anti-thyroid peroxidase monoclonal antibody was investigated by immunohistochemistry on fine-needle aspirates of 150 surgically removed thyroid nodules (20 papillary carcinomas, five follicular carcinomas, 90 colloid adenomas, nine fetal adenoma, 13 atypical adenomas, five oncocytic adenomas, six Hashimoto's thyroiditis and two Graves' disease). The percentage of positive cells has been compared to the final histological diagnosis. In samples from 113/125 benign nodules 80-100% cells presented a positive immunoreaction, whereas all samples from malignant tumors yielded less than 80% positive cells. Benign nodules exhibiting less than 80% positive cells corresponded to three degenerative colloid nodules, five atypical follicular adenomas, two oncocytomas and two thyroiditis. According to results obtained in this series, with the value of 80% as the limit for discrimination between benign and high-risk nodules, the sensitivity of thyroid peroxidase staining for diagnosis of malignancy would be 100%, its specificity 90% and its overall accuracy 92%. Thyroid peroxidase staining with monoclonal antibody MoAb47 on fine-needle aspirates is a useful adjunct to conventional cytology for the investigation of patients with thyroid nodules.

Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies.

The presence of thyroglobulin (TG) was investigated by immunohistochemistry with one polyclonal and three distinct monoclonal anti-TG antibodies in 19 primary and 15 metastatic medullary thyroid carcinoma (MTC) cases. In two primary tumors possessing a mixed trabecular and follicular growth pattern, a significant number of tumor cells were positive with the four antibodies in all parts of the tumor; these tumors were considered to be genuine mixed follicular and parafollicular tumors. The 17 other primary tumors looked like "classical" (ie, predominantly compact) MTC. Eight contained tubular or microfollicle-like structures that were consistently TG-negative. Eight contained residual entrapped normal follicles positive with the four anti-TG antibodies. In six cases isolated foci of tumor cells reacted with polyclonal antibody or monoclonal antibody 11. In 10 cases circulating TG stained positively with polyclonal antibody in vascular channels, five cases stained positively for TG with monoclonal antibody 11, four cases stained positively for TG with monoclonal antibody 7, and three cases stained positively for TG with monoclonal antibody 1. In metastases TG was found in tumor cells in only one instance, but positive reactions were obtained in vascular channels and macrophages in several cases. We conclude from this study that there is no genuine secretion of TG in classical, compact MTC, which differs morphologically and functionally from mixed follicular and parafollicular tumors secreting both TG and thyrocalcitonin.