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Background/purpose: The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. Results: The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4 ± 12.9 years. Their mean age at diagnosis was 41.8 ± 12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7 ± 9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9 ± 8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and the insulin-like growth factor 1 levels were 2.7 ± 4.9 μg/L, 2.4 ± 6.1 μg/L, and 291.5 ± 162.4 ng/mL, respectively. The remission rate assessed by random GH level (≦2 μg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0 ± 19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. Conclusion: This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly. Keywords: Acromegaly, Patient registry, Taiwan, Health outcome, Quality of life

Background: The macrofollicular variant of papillary thyroid cancer (MFVPTC) is a rare histological variant of papillary thyroid cancer (PTC), with only 71 cases reported through 2014. This study analyzed the clinical, preoperative thyroid ultrasonography (US), and fine needle aspiration cytology (FNAC) features; and therapeutic outcomes of 11 patients with MFVPTC. Methods: The records of 393 patients with histologically diagnosed follicular variant of papillary thyroid carcinoma (FVPTC), including 11 with MFVPTC, were retrospectively reviewed. Preoperative thyroid US findings, clinical presentation, treatment outcomes, and survival rates were analyzed. Result: Mean tumor size was significantly greater in patients with MFVPTC than that in those with FVPTC (4.2 ± 2.1 cm vs. 2.9 ± 1.7 cm; p = 0.016). No patient with MFVPTC had lymph node involvement, but one had a micrometastasis to the lung, which responded well to therapeutic radioiodine. All MFVPTC lesions were isoechoic on US. Eight nodules had calcifications and eight had irregular margins. FNAC showed that these tumors had low cellularity, absence or focal presence of enlarged clear nuclei, and subtle or focal nuclear features of PTC. Cells were, arranged in microfollicular pattern, with abundant colloid background. Multifocal PTCs were detected in the opposite lobe of two patients. All 11 patients with MFVPTC had excellent outcomes. No patient experienced recurrence, and survival rates were high. Conclusions: Malignant US criteria combined with FNAC features have a low preoperative diagnostic rate for MFVPTC. Surgery is recommended for patients with thyroid nodules larger than 4 cm and those with subtle and focal atypical nuclei in FNAC. Keywords: Total thyroidectomy, Thyroglobulin, Radioactive iodide, Cancer-specific mortality

This study verified the value of a computer-aided diagnosis (CAD) technique assisting in ultrasonography (US) diagnosis of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG)-avid thyroid incidentalomas on positron emission tomography. A total of 82 18FDG-avid thyroid incidentalomas from 74 non-thyroid cancer patients were retrospectively analyzed with respect to US and CAD parameters (anechoic area, hyper-echoic foci, hypo-echogenicity, heterogeneity, margin, taller-than-wide shape, eccentric area) and were compared with 38 other non-18FDG-avid nodules found in the same patient group. Fine-needle aspiration cytology or surgical intervention pathology was performed for diagnosis. No significant differences in nodule size or CAD parameters were found in 18FDG-avid nodules reported as benign, indeterminate or malignant. Significantly more taller-than-wide nodules were thyroid originating than metastatic (0.30 vs. 0.16, p

Background Serum thyroglobulin (Tg) is not a reliable tumor marker for monitoring disease status after treatment in patients with papillary thyroid carcinoma (PTC) with positive anti-thyroglobulin antibody (TgAb). The aim of this study was to evaluate the clinical role of circulating epithelial cells (CECs) in PTC patients with positive serum TgAb and undetectable serum Tg. Methods A pilot study was performed to evaluate CECs in 25 PTC patients with positive serum TgAb and undetectable serum Tg. CECs were isolated and enriched from peripheral blood with a negative selection system PowerMag. Immunofluorescence staining with anti-epithelial cell adhesion molecule (anti-EpCAM) and anti-thyroid stimulating hormone receptor (anti-TSHR) antibodies were used to define EpCAM+-CECs and TSHR+-CECs. After CECs testing, 25 patients were classified into two groups: recurrence group (n = 7) and remission group (n = 18) based on biopsy or imaging studies. The diagnostic accuracy and cutoff points of EpCAM+-CECs and TSHR+-CECs were evaluated using receiver operating characteristic (ROC) curves. The optimal cut-off values of CECs were determined by the Youden index (sensitivity + specificity − 1). Results The median numbers of EpCAM+-CECs (72.5 vs. 10.75) and TSHR+-CECs (54 vs. 5.25) were significantly increased in recurrence group compared to remission group. The area under the curve (AUC) showed good performance of EpCAM+-CECs (0.937) and TSHR+-CECs (0.825) to discriminate between recurrence and remission. The cut-off value for EpCAM+-CECs and TSHR+-CECs were set at 48 cells/ml and 10 cells/ml, respectively and showed a sensitivity (EpCAM+-CECs: 85.7%; TSHR+-CECs: 85.7%) and a specificity (EpCAM+-CECs: 100%; TSHR+-CECs: 77.8%) in predicting the recurrence. Conclusions Our study suggests CECs testing could be a potential biomarker to identify recurrence in PTC patients with positive serum TgAb and undetectable serum Tg.

Background Surgical management of Graves' disease (GD) is changing from subtotal to total thyroidectomy because the latter eliminates the risk of recurrence. However, to preserve thyroid function in a euthyroid state, subtotal thyroidectomy is still performed for GD in non-Western countries. Therefore, we designed a study to investigate the long-term outcomes in GD patients after subtotal thyroidectomy and the correlation between remnant weight and postoperative thyroid function. Materials and methods This was a retrospective cohort observation study. Between January 2005 and December 2011, 415 consecutive GD patients treated by subtotal thyroidectomy were enrolled. All data were collected from 385 patients who underwent bilateral subtotal thyroidectomy and 57 patients who underwent the Hartley-Dunhill operation. The median postoperative follow-up time was 72 months (range 12-144 months). Results The mean weight of the preserved thyroid remnant was 5.1 g. Persistent or recurrent hyperthyroidism was observed in 119 (28.7%) patients. The median time of recurrence was 36 months (range 12-120 months). Hypothyroidism developed in over 50% of patients. A euthyroid state was achieved in only 19.3% of patients, and the rate did not increase significantly as remnant weight increased. Based on a Cox regression analysis, the remnant weight is an independent risk factor for persistent or recurrent hyperthyroidism (hazard ratio: 1.323, 95% confidence interval: 1.198-1.461, P Conclusions Subtotal thyroidectomy with the intent to maintain a euthyroid state is not an optimal surgical strategy for the definitive treatment of GD because the persistence or recurrence rate is high and the euthyroid rate is lower than expected.

Aims The aims of the present study were to investigate the co-occurrence of depressive symptoms and cognitive impairment in community dwelling older adults with diabetes and its relationship with specific diabetes self-care behaviors. Methods We analyzed data from two national samples of older adults (65 years or older) with self-reported physician-diagnosed diabetes (N = 1034), who participated in the 2005 or 2009 National Health Interview Survey in Taiwan. The Mini-Mental State Examination was used to assess cognitive function. The Center for Epidemiologic Studies Depression Scale was used to assess depressive symptoms. The study assessed self-care behaviors including medication adherence, exercise, healthy diet, and self-monitoring of blood glucose. Results In this study, 8.8% of participants with diabetes had both depressive symptoms and cognitive impairment. After adjusting for other factors, participants with both cognitive impairment and depressive symptoms were less likely to exercise (Prevalence Ratios (PR) = 0.66; 95% Confidence Intervals (CI) = [0.47–0.91]; P-value = 0.011), and have a healthy diet (PR = 0.82; 95%CI = [0.70–0.96]; P-value = 0.012). Conclusions Our results illustrate the high prevalence of combined depressive symptoms and cognitive impairment and that this combination is associated with worse self-care behaviors in older adults with diabetes. These findings highlight the difficulty that some older adults with diabetes may have in maintaining self-care behaviors in the presence of depressed mood and cognitive impairment, particularly in the areas of diet and exercise. The results emphasize the importance of providing more support for these aspects of self-care to such older adults.

Objective The aim of this study was to investigate the prevalence, characteristics, and acute care utilization of community dwelling disabled older adults with an absence of help for activities of daily living (ADL). Methods We analyzed cross-sectional data from a nationally representative sample of people aged 65 years and over (n = 2904) participating in the 2009 National Health Interview Survey in Taiwan. Disability was defined as self-reporting a lot of difficulty or complete inability to carry out one or more ADL tasks. Participants with disability were asked whether they received help in the form of personal assistance or assistive devices to complete ADL tasks, with a yes response indicating the presence of help and a no response indicating the absence of help. Hospitalization and emergency department visits was assessed as a dichotomous variable (any or none), respectively. Results An absence of available help for ADL disability was reported in 16.6% of disabled older adults. Disabled older adults reporting an absence of help were more likely to be female. After adjustment for other factors, compared to older adults without disability, older adults with disability not receiving help for ADL tasks were highly related to hospitalization (OR = 4.57; 95%CI = [1.51–13.82]) and emergency department visits (OR = 3.52; 95%CI = [1.15–10.76]) during the past year, respectively. Conclusions We found that there is high prevalence of absence of help to perform ADL tasks in older adults with disability, and that this absence of help for ADL disability is associated with a greater burden of acute care utilization than those without disability.

Background This study examines whether the measurement of circulating epithelial cells (CECs) facilitates the identification and follow-up of a patient with thyroid cancer. Methods A 29-y-old woman with no cancer history was enrolled as a healthy control in a CEC study. CECs were enriched from the peripheral blood by the negative selection system PowerMag. Various medical examinations were performed on the patient to establish the diagnosis and to follow-up her disease status during treatment. Results This patient had unexpectedly high CEC counts that were sustained for more than two weeks. Thyroid gland ultra-sonography revealed lesions in the left lobe that could not be confirmed as cancer by magnetic resonance imaging, 18 F–fludeoxyglucose-positron emission tomography–computed tomography or cytopathological analysis, but were histologically confirmed after thyroidectomy as papillary thyroid microcarcinoma. Both the CEC count and serum thyroglobulin (Tg) concentration were significantly decreased after thyroidectomy, and they and the patient's disease status were correlated during remnant ablation therapy. The CEC count returned to normal when the patient was disease-free 10 months after thyroidectomy. Conclusions CEC testing facilitates the identification of individuals at risk for cancer. Longitudinal follow-up of the CEC count may complement serum Tg testing for monitoring the status of patients with thyroid cancer.

The survival rate of anaplastic thyroid cancer (ATC) is still very poor due to its fast growth and high metastatic potential. Currently, no effective treatment is available. The active form of vitamin D3, 1α,25(OH)2D3, has been shown to have a anti-metastatic effect in pre-clinical studies, however induction of hypercalcemia hampered its clinical application. The new class of less-calcemic vitamin D analog, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), is much more potent than 1α,25(OH)2D3 to repress cancer growth and metastasis in a variety of cancers. In this study, we demonstrated that both 1α,25(OH)2D3 and MART-10 could effectively inhibit the migration and invasion of ATC cells, 8305C and 8505C, with MART-10 much more potent than 1α,25(OH)2D3. The anti-metastatic effect of 1α,25(OH)2D3 and MART-10 on ATC cells is mediated by reversal of cadherin switch (upregulation of E-cadherin and downregulation of N-cadherin), which led to the attenuation of EMT process, and decrease of F-actin formation. We further showed that the expressions of Slug, the EMT-related transcriptional factor, and MMP-9 were inhibited by 1α,25(OH)2D3 and MART-10 in 8505C cells, but not in 8303C cells. Since metastasis is the important cause of ATC-related death, our results strongly encourage the further in vivo study of MART-10 application against ATC.

ObjectivePatients with diabetes mellitus have an increased risk of coronary heart disease; however, many patients with diabetes remain untreated or undertreated for coronary heart disease risk factors. The incidence of type 2 diabetes is rapidly increasing in Taiwan. The aim of this study was to assess the lipid-lowering effects of atorvastatin in Taiwanese diabetic patients with hyperlipidemia.Materials and MethodsThis 12-week open-label study, conducted at six hospitals in Taiwan, included 157 outpatients (aged 18–80 years old) with type 2 diabetes and concomitant hyperlipidemia. Individuals were randomized (1:1:1) to three dosage groups, as follows: 52 patients received 10 mg of atorvastatin per day; 52 patients received 20 mg of atorvastatin per day; and the remaining 53 patients received 40 mg of atorvastatin per day. Treatment targets were established according to the recommendations of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III. The response was evaluated by Cochran-Mantel-Haenszel tests. The change from the baseline level of all lipid parameters and high-sensitivity C-reactive protein (hs-CRP) was determined through analysis of covariance and was assessed at each time point.ResultsThe primary endpoint—a low-density lipoprotein-cholesterol (LDL-C) response of >100 mg/dL at Week 12—was achieved in a dose-dependent manner. The percentage of patients improving to this level was higher in the 20 mg/day group (82%) and 40 mg/day group (82%) than in the 10 mg/day group (56%; p = 0.002). The percentage of patients achieving the more aggressive LDL-C goal of >70 mg/dL was 9.6%, 31.4%, and 47.1% in the 10 mg/day, 20 mg/day, and 40 mg/day groups, respectively (p

In this paper, we present a fast algorithm for joint estimation of the two-dimensional (2-D) directions of arrival (DOAs) and frequencies of the incoming signals in wireless communications using a hierarchical space-time decomposition (HSTD) technique. Based on the HSTD, the proposed algorithm makes use of a sequence of one-dimensional (1-D) Unitary estimation of signal parameters via rotational invariance technique (ESPRIT) algorithms to estimate these parameters alternatively in a hierarchical tree structure. Also, in between every other 1-D Unitary ESPRIT algorithm, a temporal filtering process or a spatial beamforming process is invoked to partition the incoming signals into finer groups stage by stage to enhance the estimation accuracy as well as to alleviate the contaminated noise. Furthermore, with such a tree-structured estimation scheme, the pairing of these parameters is automatically determined without extra computational overhead. Simulation results show that the new algorithm provides satisfactory performance but with drastically reduced computations compared with previous works.

Ultrasound and fine needle aspiration cytology are advocated as first-line examinations for the assessment of thyroid nodules. This review investigates the incidence of thyroid cancer in thyroid nodules after ultrasonographic examination. Furthermore, patient characteristics, histological patterns, and therapeutic results among patients who received thyroid ultrasound and fine needle aspiration cytology are discussed. The incidence of thyroid cancer in thyroid nodules, as detected by thyroid ultrasound, was found to range from 7.9% to 32.7% depending on the selected population. The incidence of thyroid cancer in thyroid nodules reported depends on the studied cohort, ethnic group, age, sex and iodine intake. Radiation exposure is also an important factor. Of the 6,330 patients with thyroid nodules who underwent surgical treatment, benign lesions were observed in 75.5% (4,782 cases) of the cases. Papillary thyroid carcinoma was observed in 79.8% (1,236 cases) of the 1,548 malignant cases. The percentage of malignancy was found to increase after the age of 50 in both men and women. A decrease in tumor size correlated with decreased cancer mortality; however, the beneficial effects of a small tumor size were not seen in older patients. Radiation-exposed populations and thyroid nodules or thyroid cancer were major problems from the atomic bomb in World War II and the Chernobyl nuclear accident. However, most occupational radiation exposure studies have not illustrated this harmful effect of radiation. In summary, over the time course in the diagnosis of thyroid cancer in nodules, there is a trend of decrease in tumor size and increase in the patient's age. The diagnosis and treatment of non-well-differentiated thyroid cancer in ageing patients is a major obstacle that needs to be overcome in the future.

Purpose This retrospective study analyzed the role of total or near-total thyroidectomy and adjuvant radioactive iodide (131I) therapy in papillary thyroid carcinoma patients with disease more advanced than T1N0M0. Methods The study analyzed 1055 consecutive papillary thyroid cancer patients, 825 women and 230 men, who underwent near-total or total thyroidectomy, thyroid remnant ablation with 131I, and follow-up at Chang Gung Medical Center in Linkou, Taiwan. Patients with T1N0M0 stage tumors were excluded. Patients were categorized into four groups according to treatment outcome. Group A was disease-free patients with negative results of 131I whole body scan, undetected serum thyroglobulin (Tg) and Tg antibody, and no recurrence. Group B patients had no clinical evidence of persistent or recurrent thyroid cancer but were not in disease-free status. Group C were patients with cancer tissue persisting after surgery. Group D were patients suffering cancer recurrence after surgery and 131I ablation. Results After a mean follow-up period of 10.1 ± 5.4 years (median: 9.5 years), 46 (4.36%) patients died of thyroid cancer. Nine Group A cases with persistent or recurrent cancer were treated until achieving disease-free status. Group C patients received the highest 131I dose but had a 25.7% mortality rate. In Group D, the mean duration from first thyroidectomy to recurrence was 5.1 ± 0.4 years and ranged from 0.8 to 18.7 years. Four of 56 (7.1%) patients with recurrent local neck cancer died of thyroid cancer and 12 (21.4%) died of thyroid cancer with distant metastases. Conclusions Radioactive iodide therapy effectively controlled papillary thyroid carcinoma after neck surgery in 23.9% of patients. After surgery and 131I treatments, most patients with persistent or recurrent local-regional neck cancer were free of relapse; the cancer mortality rate was 19.0%.

Summary Objective To examine the associations between watching television and physical activity with the metabolic syndrome and its components. Study design Cross-sectional study. Methods This study was conducted among 358 subjects recruited from the Department of Health Management of Chang Gung Medical Centre in Linkou. After adjustment for gender, age and body mass index (BMI), the odds ratios (ORs) of the metabolic syndrome and its components were analysed for relative daily energy expenditure groups and time spent watching television categories. Results After adjustment for gender, age and BMI, the OR of the metabolic syndrome in the most active subjects compared with the least active subjects was 0.27 [95% confidence interval (CI)=0.08–0.88; P =0.030]. There was inconclusive evidence of an association between watching television for more than 20 h/week and presence of the metabolic syndrome (OR=2.99; 95% CI=0.83–10.84; P =0.095). Conclusions Physical activity was a significant protective factor for presence of the metabolic syndrome and low levels of high-density-lipoprotein cholesterol. Watching television was positively associated with greater odds of high levels of triglycerides and fasting glucose. This study emphasized the importance of reducing the time spent watching television and increasing the level of physical activity for prevention of the metabolic syndrome.

Platelet-derived growth factor receptor (PDGFR) can bind to its ligand and consequently possess a kinase activity, and which is associated with the carcinogenesis of different cell types, including astrocytomas, oligodendrogliomas, and glioblastoma. In a cDNA microarray analysis, we observe the over-expressed mRNA of both PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells. And the elevated protein expressions of PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells were also confirmed by a Western blot analysis. The phosphorylation of PDGF-alpha receptor evaluated by an antibody against Tyr 720-phosphate was found in thyroid carcinoma cells. The tyrosine kinase activity of PDGF-alpha receptor was inhibited by tyrphostin AG1295 and showed a dose-dependent inhibition for the proliferation of thyroid carcinoma cells. These findings imply that autocrine activation of PDGF-alpha receptor plays a crucial role in the carcinogenesis of thyroid cells.

Identifying a tumor marker that can help distinguish benign from malignant thyroid tumors is crucial, because up to 30% of thyroid fine-needle aspirations (FNA) are diagnosed as 'suspicious' or follicular neoplasm for malignancy. Recently, the detection of human telomerase reverse transcriptase (hTERT) gene expression in thyroid FNA samples has been identified as a promising diagnostic marker in distinguishing benign and malignant thyroid tumors. Twenty-seven FNA samples from thyroid tumors that were suspected to be malignant were collected preoperatively, hTERT gene expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR), and the cytological and histological results were compared. The results demonstrated that 13 (92.8%) of 14 thyroid carcinomas, including eight of eight papillary, three of four follicular, and two of two Hürthle cell thyroid carcinomas have corresponding FNA samples that were positive for hTERT. Meanwhile, eight (61.5%) of 13 benign thyroid nodules, including three of six nodular goiter, two of two Graves' disease, two of two Hürthle cell adenomas, and one of three follicular adenomas were positive for hTERT. In conclusion, hTERT was more prevalent in malignant thyroid FNA samples than in the benign thyroid FNA samples. Notably, the extent of the differences in hTERT expression between benign and malignant follicular thyroid tumors require further investigation. Moreover, further information including semi-quantitative real-time RT-PCR, is required to verify whether hTERT mRNA expression could serve as an adjunctive molecular marker for the preoperative diagnosis of thyroid malignancies.

Human sodium iodide symporter (hNIS) is an intrinsic membrane protein with 12 transmembrane regions, which shows homology to other sodium-dependent transporters. There is controversy as to the amount of hNIS expression in different kinds of human thyroid cancer tissues and cell lines. In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect mRNA of hNIS in various fresh normal, benign tissues and malignant human thyroid tissues. The forward primer was nested hNIS-5' primer containing the sequences: ACCTGGAAATGCGCTTCAGC. The reverse primer was nested hNIS-3' primer containing the sequences: AAGCATGACACCGCGTGCCA. The results revealed three of three normal tissues, six of eight nodular hyperplasia, two of two hyperthyroidism, one of three follicular adenomas, five of ten papillary thyroid carcinomas, one of one follicular carcinoma and zero of one metastatic follicular tissues demonstrated positive results for hNIS in thyroid epithelial cells. A higher percentage of positive results of the symporter mRNA were found in normal benign thyroid tissues and the thyroid tissues of hyperthyroidism, and nodular hyperplasia (84.6%); however follicular adenoma, papillary and follicular thyroid carcinomas demonstrated a lower percentage of expression in the RT-PCR studies (46.7%). Serum thyrotropin levels and the degree of differentiated components presented in cancer tissues have been mentioned as important factors for hNIS expression in the cancer tissues. The discrepancies of the expression of hNIS in in vivo and in vitro studies need further investigation. In conclusion, hNIS was found in higher ratios in normal and benign thyroid tissues than in the malignant tissues. In addition, the RT-PCR technique hNIS did not detect the transporter in most papillary thyroid cancer tissues.

In our previous studies we have shown that somatostatin and octreotide modulate the function of peritoneal macrophages and Kupffer cells in noncirrhotic livers. However, the effects of somatostatin on the Kupffer cells in cirrhotic livers are not known. In the present study, Kupffer cells, obtained from male rats with carbon tetrachloride-induced cirrhotic livers, were treated in vitro with somatostatin or octreotide and their effects on the release of nitric oxide, tumor necrosis factor-alpha (TNF-alpha) and peroxide (H2O2) determined. At concentrations of 10(-13) or 10(-10) to 10(-6) M of somatostatin or 10(-12) to 10(-10) M, or 10(-6) M of octreotide, the amount of nitric oxide released by Kupffer cells was significantly suppressed relative to that of untreated cells. Kupffer cells treated with less than 10(-12) M or greater than 10(-12) M of somatostatin or octreotide released less TNF-alpha compared to the untreated controls. In addition, zymosan-induced H2O2 release by Kupffer cells treated with 10(-9) to 10(-7) M somatostatin or with 10(-15) to 10(-13) M and 10(-9) to 10(-7) M of octreotide was greater than that of the untreated controls. These findings demonstrate that somatostatin and octreotide modulate the release of nitric oxide, TNF-alpha and H2O2 by Kupffer cells in cirrhotic livers depending on the concentrations of hormones used.

The pattern of p53 protein expression was examined in 92 cases of thyroid carcinoma. When the cases were divided into two groups with regard to their cytoplasmic staining only or nucleus staining only, the frequency of the nucleus staining group was significantly higher in the poorly differentiated carcinoma (PDC) and undifferentiated carcinoma (UDC) groups (10.5% and 25%) compared with the other groups of histologic subtype (0%). The results suggest positivity in nucleus staining for p53 may be a marker for the biologically worse carcinomas, PDC and UDC, however, tumors showing only cytoplasmic staining of p53 favor a fair prognosis. In this paper, we also elucidate the spectrum of genotypic aberrations of p53 in each histological subtype. Of 92 thyroid tumor samples analyzed, the overall frequency of p53 mutation was 8.5%. The mutations occurred in 4.35% (2/46) ot WDC, 17.2% (5/29) of PDC, and 16.7% (1/6) of oncocytic carcinoma. Two of five PDC cases and one papillary carcinoma revealed point mutations in exon 8 as follows; GTG (val) to CTG (leu) at codon 272 in case 23T, CGA (arg) to CCA (pro) at codon 306 in case of 30T, and CGG (arg) to AGG (arg) at codon 282 in case 28T. All of the p53 mutations detected were represented by single nucleotide changes including two missense and one silent mutation. In contrast to the missense mutations found in PDC, it is interesting to note that the silent mutation was checked in 28T of well differentiated papillary carcinoma. These results represents molecular evidence that p53 gene aberration associated with overexpression of the mutant form of p53 protein plays a crucial role in the biologically aggressive subtypes of thyroid carcinoma, and point mutation only was not sufficient to be a prognostic marker for the biologically aggressive malignancy of thyroid tumors. There was no p53 gene aberration found in four cases of undifferentiated carcinoma (UDC) studied. The results suggest that other unknown factors should be responsible for the aggressiveness in some UDC of thyroid carcinoma except overexpression of p53.