Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid

Vascular endothelial growth factor (VEGF) is an angiogenic factor, and its expression has been rarely demonstrated in thyroid tumors. We, therefore, investigated the expression of VEGF messenger RNA (mRNA) and production of VEGF protein in cell lines from human primary and metastatic follicular (FTC-133, FTC-236, and FTC-238), papillary (TPC-1), Hürthle cell (XTC-1), and medullary thyroid cancers (MTC-1.1 and MTC-2.2), and in human thyroid tissues (papillary, follicular, medullary, and Hürthle cell cancers, follicular adenomas, and Graves' thyroid tissue) by Northern blot, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) studies. All thyroid cell lines expressed a 4.2-kilobase VEGF mRNA. The VEGF mRNA levels were higher in the thyroid cancer cell lines than in primary cultures of normal thyroid cells, and higher in thyroid cancers of follicular than those of parafollicular cell origin. The VEGF mRNA levels were similar in primary and metastatic thyroid tumors. Immunohistochemical staining and Northern blot analysis of the cell lines correlated positively, thus thyroid cancer cell lines stained more intensely than normal thyroid cells and follicular tumor cells more intensely than parafollicular tumor cells. Again, no difference was noted in VEGF staining between primary and metastatic thyroid tumors. Deparafinized sections of papillary, follicular, and Hürthle cell cancers also stained much stronger than those of medullary thyroid cancers, benign, or hyperplastic (Graves' disease) thyroid tissue. Thyroid cancer cell lines (XTC-1 > TPC-1 > FTC-133 > MTC-1.1) also secreted more VEGF protein as measured by ELISA than did normal thyroid cells. VEGF secretion of cell lines derived from primary and metastatic thyroid tumors were similar. VEGF mRNA is therefore expressed, and VEGF protein is secreted by normal, hyperplastic, and neoplastic thyroid tissues. The higher levels of VEGF expression in differentiated thyroid cancers of follicular cell origin suggests a role in oncogenesis.     

Histopathological and immunohistochemical studies on medullary thyroid carcinoma

In order to study the multidifferentiation of medullary carcinoma of the thyroid gland (MCT), 24 cases of MCT were examined for the presence of immunoreactive calcitonin (CT), thyroglobulin (Tg), chromogranin A (CgA), somatostatin (SS), serotonin (5-HT), S-100 protein (S-100), neuron-specific enolase (NSE), vasoactive intestinal polypeptide (VIP), adrenocorticotrophin (ACTH) and neurofilament protein (NF) by using immunohistochemical ABC methods. Results showed that CT-immunoreactive cells were present in all tumors. Tg was present in three tumors. 23 cases contained CgA-immunoreactive cells. 14 tumors contained 5-HT-immunoreactive cells, 10 cases were immunoreactive to NSE and SS. 4 tumors contained VIP-immunoreactive cells and only one cases was positive for S-100. The demonstration of immunoreactivity for multiple antigens in 24 cases suggests that the origin of medullary thyroid carcinoma may originate from neuroectoderm cells potentially capable of producing numerous hormone substances. In addition, as the neoplastic cells in 12% of the tumors containing hormone substances as well as thyroglobulin, it is suggested that follicular epithelial differentiation and mixed medullary thyroid carcinoma may be more common than previously suspected. Recent studies indicate that mixed carcinoma of the thyroid may be derived from common stem cells in posterior branchia capable of differentiating into both follicular and parafollicular tumor cells.     

Local staging of esophageal cancer using endoscopic magnetic resonance imaging: prospective comparison with endoscopic ultrasound

Thyroid cancer is associated with abnormal thyroid peroxidase (TPO) expression as shown by abolition of immunodetection by monoclonal antibody 47 (Mab 47). The purpose of this study was to determine the relation of this abnormality with differentiation and proliferative potential of follicular tumors evaluated by analyzing thyroglobulin (TG) expression and proliferative cell nuclear antigen (PCNA) index. TPO, TG, and PCNA immunostaining were performed in a series of 30 thyroid follicular tumors ranging from adenoma to invasive carcinoma. Our findings confirmed that TPO abnormalities and PCNA index were correlated with malignancy, and that PCNA as well as TPO could be used to determine the growth potential of follicular proliferations in fine-needle aspirates. The most discriminant parameter was the ratio between the percentage of Mab-47 and PCNA positive cells. Ratios under 0.6 were correlated with malignancy in 90% of the cases, with only 3 cases of atypical adenomas being misdiagnosed as carcinomas. An inverse correlation was found between TPO and PCNA expression, but TG, which persisted at high levels in several actively growing follicular carcinomas, did not appear directly linked to cellular proliferation. These findings confirm that, unlike a decrease in TG synthesis that merely reflects the progressive loss of differentiation occurring in high-grade proliferations, alteration of TPO is an early marker of thyroid follicular tumors, closely related to acceleration of tumor growth in the first stages of malignant transformation.     

Replacement of linoleic acid with alpha-linolenic acid does not alter blood lipids in normolipidaemic men

A retrospective immunohistochemical study of 33 cases of primary thyroid carcinomas and 5 cases of metastases to thyroid was carried out. The immunostaining for thyroglobulin and calcitonin was done by peroxidase-anti-peroxidase (PAP) technique. The optimum staining results were obtained by proper standardisation of the staining procedure and reagents. The sections were systematically evaluated for immunostaining intensity and distribution. The observations revealed that thyroglobulin and calcitonin could be useful as sensitive and specific histogenetic markers for follicular and parafollicular cell derived thyroid carcinomas respectively. However, there was no absolute correlation between thyroglobulin positivity and grade of differentiation. The immunostaining could not differentiate follicular adenoma from follicular carcinoma. More extensive study using other markers may be useful for better patient management.     

Imaging of small renal tumors

The increased incidence of detection of small renal tumours, less than or equal to 3 cm in diameter, is related to the generalization and improvement of radiological techniques. Many asymptomatic renal tumours are discovered by ultrasonography and computed tomography. Medical imaging is now able to identify simple cysts (morphological characters, absence of blood supply), angiomyolipomas (demonstration of the fatty contingent) and other solid renal tumours (tumour enhancement on computed tomography). Plain, followed by postcontrast CT looking for contrast enhancement of the lesions is the examination of choice in this context. MRI with Gadolinium injection looking for neoplastic enhancement can be useful in doubtful cases. Medical imaging is able to reliably demonstrate the vascular nature of solid lesions, but cannot distinguish between renal cancer, oncocytoma or another benign solid tumour. Medical imaging allows precise preoperative mapping when partial nephrectomy is envisaged.     

Overexpression of the HIP gene coding for a heparin/heparan sulfate-binding protein in human thyroid carcinomas

A subtractive library screening was performed to identify changes in gene expression that occur during the process of neoplastic transformation of thyroid cells. A cDNA library was constructed from a human thyroid papillary carcinoma cell line (NPA) subtracted with cDNAs from normal thyroid cells (HTC 2). The differential screening of this library lead to the isolation of 39 cDNA clones; six of them showed homology with a recently isolated gene, named HIP, that codes for a protein belonging to a novel class of heparin/heparan sulfate-binding proteins. Northern blot analysis revealed HIP gene overexpression in all of the human thyroid carcinoma cell lines analyzed, as compared to the HTC 2 cells. HIP expression was particularly abundant in the anaplastic carcinoma-derived cell lines. The analysis of surgically removed thyroid tumors showed overexpression of HIP gene in all of the carcinomas, independent of the histotype, although the largest increase in HIP expression was observed in the undifferentiated forms. In contrast, none of the benign adenomas or normal thyroid tissues showed HIP overexpression. To establish the role of HIP overexpression in cell transformation, the NPA cell line was transfected with an eukaryotic expression vector carrying the HIP gene in the antisense orientation. Stable transfectants expressed reduced HIP mRNA levels and showed morphological changes, such as becoming spindle-shaped and growing scattered. The growth rate of the antisense clones was greatly reduced compared to the NPA cells transfected with the backbone vector. Taken together, these results indicate that HIP gene overexpression is associated with thyroid carcinogenesis and strongly suggest its involvement in thyroid cell growth regulation.     

Repeated hepatectomies for recurrent follicular dendritic cell tumour of liver: a case report

Follicular dendritic cell tumour is a very rare tumour of unknown aetiology. We report a case of follicular dendritic cell tumour of liver which was treated with extended right hemihepatectomy but recurred twice in the remaining left lobe within 3 years. The recurrent tumours were removed by further liver resection. The mainstay of treatment for this rare tumour is surgical resection.     

Clinicopathological study of clear-cell tumors of the thyroid: an evaluation of 22 cases

Twenty-two cases of partial or wholly composed clear-cell thyroid tumors were reviewed to differentiate between a primary nodule and metastatic clear-cell renal carcinoma in the thyroid. Pathological reevaluation of HE-stained specimens, immunohistochemical observation using anti-thyroglobulin (TG) antibody, and periodic acid-Schiff (PAS) staining were performed. The pathological characteristics in metastases from the kidney have a greater tendency to demonstrate a strikingly clear cytoplasm with small nuclei, rich vascularization, and a trabecular arrangement of tumor cells than do primary thyroid cases. The immunohistochemical TG staining in conjunction with PAS staining for the recognition of follicular colloid could provide much more reliable information of primary cases compared to that using TG staining alone. Clinically, in primary cases, the female:male ratio is substantially higher while the mean age is lower than in metastatic cases reflecting differentiated thyroid carcinoma. In conclusion, immunohistochemical staining for TG with PAS staining for the recognition of follicular colloid proved to be the most sensitive method for identifying primary clear cell thyroid tumors. In addition, a careful assessment of past and/or present kidney disorders to rule out metastatic renal cell carcinoma is advisable. Age, gender, and physiological findings are also informative when differentiating between them.     

Diagnosis and therapeutic management of 18 patients with prostatic abscess

Fifty-one thyroid tumours and tumour-like lesions were analysed for instability at ten dinucleotide microsatellite loci and at two coding mononucleotide repeats within the transforming growth factor beta (TGF-beta) type II receptor (TbetaRII) and insulin-like growth factor II (IGF-II) receptor (IGFIIR) genes respectively. Microsatellite instability (MI) was detected in 11 out of 51 cases (21.5%), including six (11.7%) with MI at one or two loci and five (9.8%) with MI at three or more loci (RER+ phenotype). No mutations in the TbetaRII and IGFIIR repeats were observed. The overall frequency of MI did not significantly vary in relation to age, gender, benign versus malignant status and tumour size. However, widespread MI was significantly more frequent in follicular adenomas and carcinomas than in papillary and Hürthle cell tumours: three out of nine tumours of follicular type (33.3%) resulted in replication error positive (RER+), versus 1 out of 29 papillary carcinomas (3.4%, P = 0.01), and zero out of eight Hürthle cell neoplasms. Regional lymph node metastases were present in five MI-negative primary cancers and resulted in MI-positive in two cases.     

Expression of osteonectin mRNA in human breast tumours is inversely correlated with oestrogen receptor content

Osteonectin is a secreted glycoprotein which is detected in a number of normal and neoplastic human tissues in vivo. It is an extracellular matrix (ECM)-associated protein which is postulated to regulate cell migration, adhesion, proliferation and matrix mineralisation and previous reports suggest that it may be modulated by steroid hormones in target tissues. The aim of this study was to measure osteonectin mRNA and protein expression in breast tumour biopsies and compare these with oestrogen (ER) and progesterone receptor (PR) levels in the same tumours. An inverse correlation was seen between osteonectin mRNA expression and ER level. Samples with low ER protein expression had a mean osteonectin mRNA level which was almost 4-fold greater than the mean level of expression observed in tumours containing high concentrations of ER protein. This inverse correlation was statistically significant. Despite the strong inverse relationship between osteonectin mRNA levels and tumour ER content, no correlation was seen when osteonectin protein concentration was measured in tumour cytosols on immunoblots and compared to ER and PR levels in the same tumours. However, since it is a secreted protein, osteonectin protein expression may not reflect cellular osteonectin levels in breast tumours. In summary, these data suggest that ER-mediated suppression of osteonectin gene expression may contribute to the less aggressive characteristics associated with receptor-positive tumours and that loss of ER expression may lead to over-expression of osteonectin and contribute to a poorer differentiated, more invasive phenotype.     

Sects, sectarisms and authentic spiritual pathways: can we learn to discern between them in order to counsel?

AIMS: We studied 12 cases of hyalinizing trabecular tumour of the thyroid gland (HTT) with the aim of reviewing the cytological, histological and immunophenotypic features and of investigating the relationships of HTT with other thyroid neoplasms. METHODS AND RESULTS: Eleven patients were female and one male, aged 8-74 years (median 58). Ten cases had a benign behaviour, while two cases were locally aggressive. Of the latter, one developed distant metastases and the other is a recent case. All patients are alive 6-311 months after diagnosis. Cytologically, HTT was characterized by hypercellular smears with aggregates of roundish cells having features of papillary carcinoma (nuclear grooves, vacuoles) and fragments of fibrous tissue. Histologically, prominent nesting, trabecular growth patterns and a hyaline stroma (partly positive for laminin and collagen type IV) were found. One case was associated with a papillary microcarcinoma. Two additional cases had extensive areas of papillary carcinoma. In one of these, hyalinized papillary stalks were observed. All tumours contained thyroglobulin but not calcitonin. High molecular weight cytokeratin (a marker of papillary carcinoma) was focally positive in 4/12 cases only and thyroperoxidase (a marker of follicular adenomas, but not of papillary carcinoma) was found in 3/12 cases. CONCLUSIONS: The immunophenotypic profile and the morphological features suggest that HTTs are an heterogeneous group of tumours, some of them probably representing variants of papillary carcinoma with hyalinized stroma.     

Primary tumours of the greater omentum

Primary tumours of the greater omentum are very rare. Ultrasound allows the detection and characterization of such lesions, but determination of their precise anatomical location is usually difficult by US. Computed tomography determines the omental origin of the tumour. Thus, when US reveals an abdominal tumour of unknown origin, the possibility of an omental tumour, although rare, must be kept in mind and CT should be performed.     

Thyroid gland carcinoma

Carcinoma of the thyroid is a rare tumour, comprising approximately 1% of human malignancies. Thyroid carcinoma is classified according to its origin (thyroid follicular cell or calcitonin-producing C cell) and grade of differentiation (differentiated, poorly differentiated or anaplastic). Due to their different biology, genetical background and clinical course, which result in fundamentally different therapeutic strategies, the various types of thyroid carcinoma have attracted a lot of interest by both clinicians and pathologists. This review article deals with the most important aspects (definition, epidemiology, clinical course, prognosis, differential diagnosis and genetic background) of the various thyroid carcinomas.     

Clinical significance of clonality in thyroid nodules

BACKGROUND: Many different neoplastic and hyperplastic thyroid diseases present with clinically apparent thyroid nodules. Clonality analysis indicates whether a nodule arises from the polyclonal proliferation of a group of cells or forms a clone from a genetically altered cell and thus provides objective information on the origin of the thyroid nodules. Clonality was studied in thyroid nodules using the polymerase chain reaction (PCR) assay in the X-linked human androgen receptor (HUMARA) gene by random X chromosome inactivation in women. METHODS: DNA samples were obtained from 28 nodules in 21 women. All nodules and non-tumour thyroid tissues were fractioned selectively under a cryostat. Genomic DNA was isolated and digested with HhaI. PCR amplification of the HUMARA locus was performed using PCR mixtures containing [alpha-32P]2'-deoxycytidine 5'-triphosphate. The PCR products were analysed by denaturing gel electrophoresis. RESULTS: The HUMARA alleles were heterogeneous in 18 of 21 patients. Among the 23 nodules from 18 patients, all of the eight papillary thyroid carcinomas were monoclonal. Two solitary nodules from follicular adenomas were monoclonal. Of the 13 follicular nodules from nodular goitres, ten were polyclonal and three were monoclonal. The monoclonal follicular nodules were larger in size (3.5 versus 2.0 cm, P< 0.05) and had a tendency towards more cystic changes than polyclonal nodules. CONCLUSION: PCR-based clonality study of thyroid nodules may help to distinguish hyperplastic from neoplastic nodules.     

Hyperattenuating rim on noncontrast CT of the liver: probable peritumoral sparing of fatty infiltration

CT scans showing a hyperattenuating rim within the liver were retrospectively evaluated in 10 patients to clarify the character, aetiology and clinical significance. All patients had hepatic tumours (7 cavernous haemangiomas in 6 patients, 3 metastatic tumours and 1 hepatocellular carcinoma) as well as fatty infiltration of the liver. Typical features of the hyperattenuating rim on noncontrast CT of the liver included (1) attenuation similar to that of the spleen, (2) a circular or semicircular shape, (3) a width of a few millimeters, (4) peritumoral localization and (5) loss of visualization with contrast enhancement. No such rims were noted around hepatic tumours unassociated with fatty infiltration. Peritumoral sparing of fatty infiltration was inferred. A hyperattenuating rim on noncontrast liver CT, although rare, suggests the presence of a hepatic tumour in fatty liver.     

Radiotherapy in the management of thyroid cancer

Surgery is the definitive and potentially curative treatment for the slow growing well-differentiated papillary and follicular carcinomas. Total (or near-total) thyroidectomy is required, together with excision of adjacent lymph nodes when involved, or a modified block dissection if there is extensive lymphatic involvement. Ablation of residual normal thyroid with radioactive iodine usually follows as this will permit subsequent whole-body I-131 scanning to exclude the presence of residual or metastatic disease. Normally such patients have an excellent prognosis and can be followed simply with serum thyroglobulin estimations. Occasionally therapeutic radioactive iodine is necessary to eradicate metastatic disease. The anaplastic carcinomas grow and metastasise with explosive rapidity. They are typically inoperable at presentation and have no ability to concentrate iodine. Prognosis is appalling with external beam radiotherapy providing only palliation. Medullary carcinoma is different again as it arises from the parafollicular or C-cells. Total thyroidectomy must be undertaken as these tumours may be multifocal; a central compartment neck resection is ideally undertaken at the same time, together with a formal block dissection if lymph node disease is found to be present. External beam radiotherapy is often required. These tumours can be inherited and produce the tumour marker calcitonin. The rarest group of thyroid cancer is the lymphomas. Like the anaplastic carcinomas, they grow very rapidly but, unlike the former, are radio-responsive. The additional use of chemotherapy is necessary when they are of advanced stage or demonstrate poor prognostic factors.     

Expression of platelet-derived growth factor (PDGF)-A, PDGF-B and the PDGF-alpha receptor, but not the PDGF-beta receptor, in human malignant melanoma in vivo

There has been considerable interest in the potential role of growth factors in the initiation and development of cutaneous malignant melanoma (CMM). Platelet-derived growth factor (PDGF) has been shown to be secreted by melanoma cell lines and by metastatic melanoma in vivo. PDGF also has been reported to stimulate the development of tumour stroma and new blood vessels. We studied the expression of PDGF and its receptors by both immunohistochemistry (IHC) and in situ hybridization (ISH) in primary and metastatic melanoma and in normal skin specimens. Cryostat sections were incubated with 35S-labelled riboprobes and antibodies for PDGF-AA, PDGF-alpha receptor, PDGF-BB and PDGF-beta receptor. Both primary and metastatic melanoma exhibited significant expression of PDGF-AA, PDGF-BB and PDGF-alpha receptor by both IHC and ISH, compared with only background expression in normal skin. We did not observe expression of PDGF-beta receptor in melanoma. Our results suggest that PDGF may function as an autocrine growth factor, as well as an angiogenesis factor, in CMM tumour development. This expression of the PDGF-alpha receptor rather than the beta receptor may be unique among solid tumours.     

Thyroid neoplasm of mid follicular-medullary type; an uncommon, particular and aggressive form: report of 3 cases

Mixed medullary and follicular carcinoma of the thyroid shares secretory and immunohistochemical features of both follicular and parafollicular thyroidal cells. We report three women, aged 34, 63 and 61 old with this type of tumor. Its diagnosis must be bore in mind in patients with thyroidal tumors and a histological appearance of a medullary or undifferentiated carcinoma. An early diagnosis of a mixed medullary and follicular carcinoma of the thyroid is important, considering its special treatment and negative prognosis.     

Structural features in the 3'' external transcribed spacer affecting intragenic processing of yeast rRNA

A total of 62 patients of gastric carcinoma were studied to find a correlation between newer prognostic indicators like cell proliferative indices including Nucleolar Organizer regions (AgNORs), Ki 67 Labelling Index and Epidermal Growth Factor Receptor (EGFR) expression with the various, histopathological criteria and compared with 30 controls of non neoplastic gastric diseases. EGFR expression was positive in 48(77.4%) cases. The Ki 67 labelling indices ranged from 0 to 50% with a mean of 21.35 +/- 17.88% among the cases. AgNOR counts ranged from 1.64 to 4.49 with a mean of 3.41 +/- 0.81 among the cases. Positive EGFR expression correlated strongly with differentiation of the tumour, poorly differentiated tumours showing a higher positivity. EGFR positivity also showed good correlation with metastasis as well as with the invasiveness of the tumour. Ki 67 labelling indices correlated significantly with metastatic status, microscopic types and degree of differentiation of the tumour. A strong correlation was observed between AgNOR counts and metastasis as well as the microscopic type of the tumour. EGFR expression correlated strongly with Ki 67 scores and weakly with AgNOR counts among the patients of gastric carcinoma.