Thyroid follicular oncogenesis in iodine-deficient and iodine-sufficient areas: search for alterations of the ras, met and bFGF oncogenes and of the Rb anti-oncogene

To gain insights into the role of iodine deficiency in favoring thyroid tumorigenesis (particularly of the follicular histotype), 22 Sicilian patients with thyroid tumors were selected for having lived permanently in either one of two areas of different iodine availability. Eleven patients (age 46.1 +/- 14.6 years, mean +/- SD; 10 females and 1 male) were from the iodine-deficient (ID) areas of the provinces of Messina and Catania (mean urinary excretion of iodine = 48.1 micrograms/24 hours). Thyroid tumors were follicular or Hürthle cell adenomas (no. = 3), follicular carcinomas (FC, no. = 4), papillary carcinomas (PC, no. = 2) and anaplastic carcinomas (no. = 2). Eleven patients (age 47.1 +/- 15.2 years; 10 females and 1 male) were from the metropolitan area of Messina, an area of relative iodine-sufficiency (IS) (urinary excretion of iodine = 95.2 micrograms/24 hours). These 11 patients had serum levels of TSH that were significantly lower than the corresponding values of the 11 patients from the ID area (0.76 +/- 0.33 vs 1.80 +/- 1.22 mU/l, p = 0.01) The tumors of the 11 patients from the IS area were: follicular or Hürthle cell adenomas (no. = 6), Hürthle cell carcinoma (no. = 1), FC (no. = 2), PC (no. = 2). Molecular biology studies revealed that both the normal as well as the tumor tissue of all 22 patients did not harbor any of the three classical activating mutations (codons 12, 13 and 61) in any of the three ras oncogenes. Similar negative results were obtained as far as loss of heterozygosity of the retinoblastoma (Rb) anti-oncogene is concerned. Immunohistochemistry studies were performed to investigate expression of c-met and basic fibroblast growth factor (bFGF) proto-oncogenes. Only one Hürthle cell carcinoma and the two PC from the IS group, and one FC and the two PC from the ID group stained for the c-met oncogene. Expression of c-met was greater (3+) in the four PC (concerning 70-80% of the tumor cells) than in the other two cancers (1+; < 5% of the tumor cells). In the IS group, positivity for bFGF was detected in 3/6 adenomas, 1/2 FC, the Hürthle cell carcinoma and the two PC. In the ID group, positivity for bFGF was observed in 2/3 adenomas, 2/4 FC, the two PC and the two anaplastic carcinomas. The 8 positive cases from the ID group had a greater level of bFGF expression than the 7 positive cases from the IS group (intensity of staining = 2.0+ vs 1.57+). Interestingly, the greatest expression of bFGF was seen in the cases with peri-tumoral lymphocytic infiltration from either group. In the ID group correlations between (i.) pre-intervention serum TSH and intensity of tumoral staining for bFGF, (ii.) serum TSH and per cent of tumoral cells reactive with anti-bFGF and (iii.) between intensity of staining for bFGF and per cent of tumoral cells bFGF +ve were higher than in the IS group. We conclude that activating mutations of ras, loss of DNA from the Rb locus and over-expression of both c-met and bFGF are of no pathogenetic relevance in driving thyroid tumorigenesis of iodine-deficient areas.     

Clinical experience in Hurthle cell tumors

In the period 1987-1997 6 patients with Hürthle cell carcinomas and 4 patients with Hürthle cell adenomas underwent primary surgical treatment (8.1% of all thyroid carcinomas). The diagnosis of Hürthle cell tumor was based on the presence of more then 75% Hürthle cells and the malignity on capsular or/and vascular invasion. All the patients with Hürthle cell cancer underwent total thyroidectomy, in three cases with Hürthle cell adenoma thyroid lobectomy was performed and in one case total thyroidectomy. Follow-up time ranged from 1 to 8 years after surgery (mean 4.5 years). There was no death and no recurrence. The Authors have studied the nuclear DNA content in Hürthle cell tumors: 3 adenomas were euploid and 1 was aneuploid, 4 carcinomas were aneuploid and 2 were euploid. The results in Authors' study of the DNA content and nuclear DNA ploidy are not uniformly consistent enough to allow a distinction between benign and malignant neoplasms and to evaluate the prognosis, but the number of patients and the follow up are still too limited.     

Polymerase chain reaction-based microsatellite polymorphism analysis of follicular and Hürthle cell neoplasms of the thyroid

Follicular and Hürthle cell carcinomas of the thyroid cannot be differentiated from adenomas by either preoperative fine needle aspiration or intraoperative frozen section examination, and yet there exist potentially significant differences in the recommended surgical management. We examined, by PCR-based microsatellite polymorphism analysis, DNA obtained from 83 thyroid neoplasms [22 follicular adenomas, 29 follicular carcinomas, 20 Hürthle cell adenomas (HA), and 12 Hürthle cell carcinomas (HC)] to determine whether a pattern of allelic alteration exists that could help distinguish benign from malignant lesions. Alterations were found in only 7.5% of informative PCR reactions from follicular neoplasms, whereas they were found in 23.3% of reactions from Hürthle cell neoplasms. Although there were no significant differences between follicular adenoma and follicular carcinoma, HC demonstrated a significantly greater percentage of allelic alteration than HA on chromosomal arms 1q (P < 0.001) and 2p (P < 0.05) by Fisher's exact test. The documentation of an alteration on either 1q or 2p was 100% sensitive and 65% specific in the detection of HC (P < 0.0005, by McNemar's test). In conclusion, PCR-based microsatellite polymorphism analysis may be a useful technique in distinguishing HC from HA. Potentially, the application of this technique to aspirated material may allow this distinction preoperatively and thus facilitate more optimal surgical management. Consistent regions of allelic alteration may also indicate the locations of critical genes, such as tumor suppressor genes or oncogenes, that are important in the progression from adenoma to carcinoma. Finally, this study demonstrates that Hürthle cell neoplasms, now considered variants of follicular neoplasms, differ significantly from follicular neoplasms on a molecular level.     

Fatty acids metabolism of rat liver after extra-lethal gamma-irradiation

OBJECTIVE: To determine if any preoperative or intraoperative factors can reliably predict malignancy in patients with Hürthle cell neoplasms. SUMMARY BACKGROUND DATA: Most experienced surgeons recommend total thyroidectomy for Hürthle cell carcinomas and reserve thyroid lobectomy for Hürthle cell adenomas. However, delineation between Hürthle cell adenoma versus carcinoma often cannot reliably be made either before or during surgery. METHODS: Medical records from 57 consecutive patients who underwent thyroid resections for Hürthle cell neoplasms between October 1984 and April 1995 at The Johns Hopkins Hospital were analyzed to determine if any factors were predictive of malignancy. RESULTS: Of the 57 patients with Hürthle cell neoplasms, 37 had adenomas and 20 had carcinomas, resulting in a 35% prevalence of malignancy. Patients with adenomas did not differ from those with carcinoma with respect to age, sex, or history of head and neck irradiation. However, patients with Hürthle cell carcinomas had significantly larger tumors (4.0 +/- 0.4 cm vs. 2.4 +/- 0.2 cm, p < 0.005). Furthermore, although the incidence of malignancy was only 17% for tumors 1 cm or less and 23% for tumors 1 to 4 cm, tumors 4 cm or greater were malignant 65% of the time (p < 0.05). Both fine-needle aspiration and intraoperative frozen section analysis had low sensitivities in the detection of cancer (16% and 23%, respectively). With up to 9 years of follow-up, there has been no tumor-related mortality. CONCLUSIONS: These data demonstrate that the size of a Hürthle cell neoplasm is predictive of malignancy. Therefore, at the time of initial exploration for large Hürthle cell neoplasms (>4 cm), definitive resection involving both thyroid lobes should be considered because of the higher probability of malignancy.     

Establishment of a highly differentiated thyroid cancer cell line of Hürthle cell origin

Hürthle cell carcinomas (HCC) of the thyroid are a variant of follicular thyroid tumors. In contrast to follicular thyroid carcinoma, HCC rarely take up radioiodine and frequently metastasize to the lymph nodes. Histologically they are indistinguishable from Hürthle cell adenomas except for evidence of invasion and metastasis. How these carcinomas develop and why they behave differently than other follicular tumors is not known. Although some differentiated thyroid cancer cell lines exist, none are from Hürthle cell tumors. We have established a well-differentiated thyroid cancer cell line from a metastasis of a HCC, designated XTC.UC1. In vitro, XTC cells display epitheloid morphology, grow with a population doubling time of 4.3 +/- 0.3 days, migrate, and invade through reconstituted basement membranes. The cells are immunoreactive for and release thyroglobulin, respond to thyrotropin (TSH) with increase of intracellular cyclic adenosine monophosphate (cAMP), proliferation, and invasion of reconstituted basement membrane, thus exhibiting characteristics of well-differentiated thyroid carcinoma. In vivo, xenografted XTC cells grow with a doubling time of 9.8 +/- 0.8 days. Tumors spontaneously metastasize to the lymph nodes and less frequently to the lungs and the liver. The cells retained their differentiated function in vivo as assessed by human thyroglobulin (hTG) secretion and immunohistochemistry. This is a first report of the establishment of a unique, highly differentiated thyroid carcinoma cell line derived from an HCC. Based on the ability to invade through reconstituted basement membrane in vitro and the potential to metastasize in vivo, this cell line may provide a unique model to study invasion and metastazation of well-differentiated thyroid cancer.     

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.     

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.     

Pediocin N5p from Pediococcus pentosaceus: adsorption on bacterial strains

Oxyphilic cell (Hürthle cell) carcinomas of the thyroid gland, variant of follicular carcinoma, are more malignant than follicular non oxyphilic cell carcinomas with a similar size and degree of invasiveness. Gross features, microscopic features of oxyphilic, clear and bicolored cells carcinomas and diagnostic techniques are related with a differential diagnosis with papillary oxyphilic cell carcinoma.     

Somatostatin receptor subtypes, octreotide scintigraphy, and clinical response to octreotide treatment in patients with neuroendocrine tumors

Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28-71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.     

The relevance of somatostatin receptors in thyroid neoplasia

111In-octreotide scintigraphy in patients with persistent medullary thyroid carcinoma (MTC) visualized tumors in about half of the surgically explored sites. Tumor visualization correlated with rapid tumor growth and large tumor volume as judged from calcitonin levels. The 111In concentration ratio between tumor (T) and blood (B) in surgically excised lymph node metastases of MTC showed a large variation, with low values for microscopic and high values for macroscopic metastases in individual patients. Three cases of MTC, Hürthle cell adenoma and papillary thyroid cancer are reported with preoperative scintigraphy, T/B ratios and Northern analyses of the surgical biopsies. Visualization of tumors was possible in the absence of sstr2 (the high affinity receptor for octreotide) with the exception of microscopic tumor growth. T/B values in the patient with Hürthle cell adenoma were similar to those found in the contralateral thyroid lobe with goitre. The relatively high uptake of 111In in benign thyroid conditions probably limits the use of octreotide scintigraphy in the diagnosis of primary tumors. The technique has certain advantages over radioiodine scintigraphy after the surgical treatment of thyroid tumors: no need for withdrawal of thyroxin substitution; a possibility to diagnose metastases of tumors that do not concentrate radioiodine (MTC, Hürthle cell cancer); and complementary information about metastatic sites of non-medullary thyroid cancer (papillary and follicular tumors).     

Expression of glutathione-peroxidase (GSH-PO) in the rat ventral prostate--effect of castration and administration of testosterone

This series retrospectively reviewed 3657 patients who received thyroid ultrasonography with fine-needle aspiration cytological (FNAC) examinations at Chang Gung Memorial Hospital during the period from January 1, 1993 to December 31, 1993. Thyroid ultrasonography studies were performed using a real-time ultrasonographic machine with a 10 MHz transducer. The aspirates were air dried and stained by the Romanowsky-based Liu method. Three hundred seventy-eight cases (10.3%) received surgical treatment after the ultrasonographic and FNAC examinations. Benign lesions were diagnosed in 269 patients. Thyroid malignancy was confirmed histopathologically in 109 cases including 76 papillary thyroid carcinomas, 17 follicular carcinomas, 5 medullary thyroid carcinomas, 3 anaplastic carcinomas, 3 Hürthle cell carcinomas, and 3 lymphomas. Another 2 cases were metastatic cancer to thyroid. The results demonstrated that 28.8% of the surgically treated patients had histopathologically proven malignancies. The incidence of thyroid malignancy was 2.98% in this study. The sensitivity of the cytological diagnosis was 79.80% and the specificity was 98.66%. The positive predictive value was 96.34%. Negative predictive value was 91.70%. The false negative index was 20.20%. The diagnostic accuracy was 92.89%. Thyroid ultrasonography with the FNAC can provide high specificity and sensitivity in differentiating malignant lesions from benign.     

Oncogenic rearrangements of the ret proto-oncogene in thyroid tumors induced after exposure to ionizing radiation

A high frequency (approximately 60%) of ret rearrangements in Chernobyl papillary thyroid carcinomas (PTC) has been reported recently. The data suggested that the radiation exposure may be a direct inducer of activating rearrangements in the ret gene. In our study, we have analyzed for the presence of RET/PTC oncogenes using the RT-PCR, XL-PCR, Southern blot and direct sequencing techniques, 39 human thyroid tumors from patients who had received external radiation for benign or malignant conditions. As controls, we studied 39 'spontaneous' tumors. Our results indicate that: 1) the overall frequency of ret rearrangements was 84% in papillary carcinomas (16/19) and 45% (9/20) in follicular adenomas; 2) in contrast with the results obtained in the Chernobyl tumors, the most frequently observed chimeric gene was RET/PTC1; and 3) all the tumors were negative for RET/PTC2. In the 'spontaneous' tumors, only the papillary carcinomas presented a ret rearrangement (15%: 3/20). Our data confirm the crucial role played by the ret proto-oncogene activating rearrangements in the development of radiation-associated thyroid tumors, and show, for the first time, the presence of RET/PTC genes in follicular adenomas appeared after external irradiation.     

Benign thyroid oncocytomas. Outcome after more than 4 years

OBJECTIVES: Occasional malignant transformation after partial thyroidectomy for Hürthle cell tumours has led certain authors to propose total thyroidectomy in all cases. The aim of this retrospective study was to evaluate outcome 4 years after partial thyroidectomy in patients with Hürthle cell tumours. METHODS: Ten patients (9 females, 1 male; mean age 45 years; age range 21-65 years) underwent thyroid surgery for Hürthle cell tumours from 1980 to 1989. Lobectomy was performed in 7, subtotal thyroidectomy in 2 and tumourectomy in 1. The extemporaneous pathology examination reported 4 apparently benign vesicular lesions, 2 apparently benign oncocyte lesions, 2 fetal adenomas, 1 thyroiditis, 1 trabecular adenocarcinoma. Pathology examination of the surgical specimen reported isolated benign oncocyte tumours in 4 cases and benign oncocyte tumours with associated vesicular adenomas in 5. In 1 case it was not possible to confirm whether the oncocyte lesion was benign or malignant. All 10 patients were seen again 6 months later for consultation and thyroid hormone assays and thyroid echography in doubtful cases. RESULTS: All patients were seen for follow-up (mean 88 months; range 47-148 months). New thyroid nodules were observed in 2 but did not require surgery. No cervical lymph node enlargement was found. CONCLUSION: The diagnosis of Hürthle cell tumour was confirmed intraoperatively in 8 of the 10 cases. No malignant transformation was observed. These findings demonstrate that total thyroidectomy cannot be indicated intraoperatively and would not appear to be indicated after partial thyroidectomy.     

Papillary Hürthle cell carcinoma (Warthin-like tumor) of the thyroid. Report of a case with fine needle aspiration findings

BACKGROUND: Papillary Hürthle cell carcinoma with lymphoplasmacytic stroma is a newly recognized variant of papillary carcinoma of the thyroid gland. Fine needle aspiration findings reveal some points that have not been reported previously. CASE: A 50-year-old female presented with a left lobe thyroid mass. Fine needle aspiration of the nodule yielded cellular smears, mostly in large and small papillary clusters of Hürthle cells, with nuclear grooves and rare nuclear inclusions in a lymphoplasmacytic background. Isolated Hürthle cell and multinucleated giant cells were also seen. Histopathologic examination of the 3-cm-diameter nodule showed papillary Hürthle cell carcinoma with lymphocytic stroma, or "Warthin-like tumor" of the thyroid, with capsular invasion. CONCLUSION: The presence of papillary clusters with nuclear features of papillary carcinoma and oxyphilic cytoplasm in a lymphoplasmacytic background should raise the diagnosis of Warthin-like tumor of the thyroid.     

p16(INK4a) gene inactivation by deletions, mutations, and hypermethylation is associated with transformed and aggressive variants of non-Hodgkin's lymphomas

The molecular mechanisms underlying the pathogenesis of aggressive lymphomas and the histological transformation of indolent variants are not well known. To determine the role of p16(INK4a) gene alterations in the pathogenesis of non-Hodgkin's lymphomas (NHLs) and the histological progression of indolent variants, we have analyzed the expression, deletions, and mutations of this gene in a series of 112 NHLs. Hypermethylation of the gene was also examined in a subset of tumors with lack of protein expression but without mutations or deletions of the gene. p16(INK4a) gene alterations were detected in 3 out of 64 (5%) indolent lymphomas but in 16 out of 48 (33%) primary or transformed aggressive variants. In the low-grade tumors, p16(INK4a) alterations were detected in 1 (4%) chronic lymphocytic leukemia (hemizygous missense mutation), 1 (6%) follicular lymphoma (homozygous deletion), and 1 (5%) typical mantle cell lymphoma (homozygous deletion). The two later cases followed an aggressive clinical evolution. In the aggressive tumors, p16(INK4a) gene alterations were observed in 2 (29%) Richter's syndromes (2 homozygous deletions), 3 (33%) transformed follicular lymphomas (1 homozygous deletion and 2 nonsense mutations), 3 (43%) blastoid mantle cell lymphomas (2 homozygous and 1 hemizygous deletions), 5 (28%) de novo large-cell lymphomas (1 homozygous deletion and 4 hypermethylations), 2 lymphoblastic lymphomas (2 homozygous deletions), and 1 of 2 anaplastic large cell lymphomas (hypermethylation). Protein expression was lost in all tumors with p16(INK4a) alterations except in the typical chronic lymphocytic leukemia (CLL) with hemizygous point mutation. Sequential samples of the indolent and transformed phase of three cases showed the presence of p16(INK4a) deletions in the Richter's syndrome but not in the CLL component of two cases, whereas in a follicular lymphoma the deletion was present in both the follicular tumor and in the diffuse large-cell lymphoma. In conclusion, these findings indicate that p16(INK4a) gene alterations are a relatively infrequent phenomenon in NHLs. However, deletions, mutations, and hypermethylation of the gene with loss of protein expression are associated with aggressive tumors and they may also participate in the histological progression of indolent lymphomas.     

Expression of the Mr 67,000 laminin receptor is an adverse prognostic indicator in human thyroid cancer: an immunohistochemical study

Increased expression of the Mr 67,000 laminin receptor (LR) is a consistent event which appears as cancer cells acquire an invasive and metastatic phenotype. The Mr 67,000 LR is one of the many laminin-binding proteins able to interact with the major glycoprotein of basement membranes, laminin. The recent development of a specific monoclonal antibody directed against the Mr 67,000 LR MLuC5 has allowed us to study large retrospective groups of human cancers with the aim of correlating the Mr 67,000 LR expression to the clinical, pathological, and survival data of the patients. A significant correlation has already been established between the increased expression of Mr 67,000 LR and survival of patients with breast, colon, ovary, lung, and endometrial cancers. In this study, we investigated the possibility that the detection of Mr 67,000 LR in thyroid human cancers could also be of prognostic value. We analyzed the expression of Mr 67,000 LR with immunohistochemistry using MLuC5 antibodies in paraffin sections of 40 benign and 170 malignant thyroid human tumors. We found that Mr 67,000 LR was not usually detectable in normal thyroid tissues adjacent to the lesion. Only 3 of the 40 thyroid adenomas examined (7.5%) presented cells positive for Mr 67,000 LR. For the malignant thyroid tumors examined, we found that 22.3% of papillary thyroid carcinomas, 38% of follicular thyroid carcinomas, 40% of poorly differentiated carcinomas, 25% of medullary carcinomas, and 58.3% of anaplastic carcinomas expressed a high level of Mr 67,000 LR. Although no correlation between the Mr 67,000 LR expression and survival was found in patients with follicular thyroid carcinomas, papillary thyroid carcinomas, anaplastic carcinomas, and medullary carcinomas, there was a significant correlation in primary thyroid cancers. Our data represent the first extensive study of the Mr 67,000 LR expression in human thyroid cancers and strongly suggest that its detection could be of prognostic value in the investigation of primary thyroid cancers.