Coexistence of chronic lymphocytic thyroiditis is associated with lower recurrence rates in patients with papillary thyroid carcinoma

Objective  The effect of coexistent chronic lymphocytic thyroiditis (CLT) on prognosis in papillary thyroid carcinoma (PTC) patients remains controversial. We evaluated the influence of coexistent CLT on prognostic outcome and the association of coexistent CLT with clinicopathological parameters.
Design  A retrospective study with a median follow-up of 70 months.
Patients and measurements  Patients with PTC who underwent total thyroidectomy followed by ¹³¹I remnant ablation between 1995 and 2003 at Asan Medical Center, Seoul, Korea were enrolled. CLT was diagnosed histopathologically.
Results  Among 1441 patients, 214 (14·9%) had coexistent CLT. A greater female preponderance was noted in the patients with CLT compared with those without CLT ( P  <   0·01). Mean tumour size in the patients with CLT was smaller than that in patients without CLT (2·0 ± 1·2 vs . 2·2 ± 1·4 cm; P  =   0·02). One hundred and fifty-one (12·3%) patients without CLT had recurrence, whereas 14 (7·1%) patients with CLT had recurrence during the follow-up period ( P  =   0·016). In patients with cervical lymph node metastases, those with coexistent CLT showed a significantly lower recurrence rate than those without CLT ( P  =   0·012). However, this association was lost on multivariate analysis adjusting for other clinicopathological predictors for recurrence.
Conclusions  In this study, CLT was commonly associated with PTC and was associated with smaller size of the primary tumour at presentation. CLT was also associated with a reduced risk of recurrence during follow-up, although this was not significant after adjustment for other prognostic factors.     

The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma

BACKGROUND: The activating BRAF(V600E) mutation is the most common genetic alteration reported in papillary thyroid carcinoma (PTC). While some reports suggest the BRAF(V600E) mutation is associated with factors predicting a poor prognosis and recurrence, this remains a controversial issue. AIM: To determine whether the presence of the BRAF(V600E) mutation is a prognostic indicator for clinical recurrence in low-risk patients with conventional PTC. PATIENTS AND METHODS: The study involved 203 conventional PTC patients who underwent total or near-total thyroidectomy followed by immediate 131I ablation of the remnants. Patients with antithyroglobulin antibodies and those with extracervical metastases at presentation were excluded. DNA was extracted from paraffin-embedded tumour specimens, and the presence of the BRAF(V600E) mutation was evaluated using PCR amplification and direct sequencing. RESULTS: The BRAF(V600E) mutation was found to be present in 149 (73.4%) of 203 patients. The BRAF(V600E) mutation was correlated with male gender (P = 0.006) and with tumour size (P = 0.005). While there appeared to be an association between the BRAF(V600E) mutation and extrathyroid extension, this did not reach statistical significance (P = 0.062). During follow-up of the 203 patients (median 7.3 years; range 0.7-10.0 years), 36 (18%) patients experienced recurrence. While univariate analysis showed the BRAF(V600E) mutation was associated with tumour recurrence (21% with mutation vs 7% without mutation; P = 0.037), this association was not shown following multivariate analyses adjusting for the clinicopathological prognostic factors of age, gender, tumour size, extrathyroid extension, multifocality and lymph node metastasis. CONCLUSIONS: Although the BRAF(V600E) mutation was found to be associated with a higher clinical recurrence of disease in low-risk conventional PTC patients, it was not an independent predictor.     

Loss of SOCS3 expression is associated with an increased risk of recurrent disease in breast carcinoma

Purpose  

Constitutive activation of JAK/STAT pathway is observed in various solid tumors and hematological malignancies. SOCS3 acts as a key negative regulator of JAK/STAT pathway and represents one of the candidate tumor suppressor genes. In the current study, we aimed to evaluate SOCS3 expression in breast carcinoma and to explore the prognostic significance of SOCS3.     

Fas (CD95) expression is up-regulated on papillary thyroid carcinoma

Thyrocyte apoptosis signaled through the Fas receptor has been proposed as a mechanism for the cytotoxicity observed in thyroiditis, but the role the Fas pathway plays in thyroid cancer is not known. We examined Fas expression in thyroid tissue derived from patients with papillary carcinoma and follicular cancer. More intense immunohistological staining for the Fas protein was observed on papillary cancer cells as compared with adjacent normal follicles. To further characterize the expression of Fas in papillary cancer, paired normal and cancerous thyroid tissues were obtained at thyroidectomy from several donors, digested, and placed into cell culture. Messenger RNA was analyzed by ribonuclease protection assays, and protein was identified by flow cytometry. Fas expression was detected at levels up to 3-fold higher in cancerous thyrocytes compared with paired normal cells. To determine whether the expressed Fas antigen was functional, thyrocytes were treated with a monoclonal IgM anti-Fas antibody (clone CH11; Upstate Biotechnology, Inc., Lake Placid, NY) in the presence of interferon-gamma and cycloheximide. Whereas both normal and cancerous thyrocytes were induced to die after this treatment, the cancerous thyrocytes were more sensitive to anti-Fas antibody. This work demonstrates that the Fas antigen is expressed and functional on papillary thyroid cancer cells and this may have potential therapeutic significance.     

Prognosis and risk stratification in young papillary thyroid carcinoma patients

Controversies remain regarding to the therapeutic methods of papillary thyroid cancer (PTC) in young patients. TNM staging and other risk evaluation system are not perfectly applicable for all young PTC patients in view of disease outcome. The aims of this study are to identify the clinical presentations, prognostic factors and risk analysis methods. From January, 1977, to June, 2006, seventy-seven patients with primary PTC younger than 20 years old at Chang Gung Medical Center in Taiwan were enrolled in this retrospective study. The patients were classified as disease-free or non-disease-free according to presence or absence of distant metastases or local recurrence at the end of follow-up. Clinical data of these patients were analyzed and compared. The average follow-up period was 10.3 years. Two patients died of PTC during the follow-up period; one died of brain metastasis, and one died of airway obstruction. Patients undergoing total thyroidectomy, especially those with disease beyond the thyroid, had better outcomes than patients not undergoing total thyroidectomy (p = 0.003). Moreover, the DeGroot clinical classification system was a better predictor of prognosis than TNM (p<0.001 vs p = 0.007). Our results suggest that prognosis for PTC is not worse in younger patients. However, patients who had undergone total thyroidectomy might have a better prognosis. Clinical classification is a good alternative classification system for predicting disease outcome in young PTC patients. Patients with confined intrathyroid lesion (相似文献   

Maspin expression is directly associated with biological aggressiveness of thyroid carcinoma.

Maspin belongs to the serpin superfamily and has been identified as a tumor suppressor because it inhibits cell motility, invasion, and angiogenesis. However, its physiological activity in carcinoma tissues seems to differ according to the origin of the carcinoma. In this study, we investigated maspin expression in thyroid neoplasms originating in follicular cells by means of immunohistochemistry. Neither normal follicular cells nor stromal cells expressed maspin. Follicular adenomas were all negative for maspin, but 12.5% of follicular carcinomas and 30.5% of papillary carcinomas were positive for it. However, the staining pattern was only focal in all positive specimens except for one and maspin-expressing cells were present mainly at the edge of carcinoma nests. Widely invasive follicular carcinomas tended to be more frequently positive for maspin than minimally invasive ones. In papillary carcinoma, maspin expression was directly linked to stage, tumor size, and extrathyroidal invasion. Papillary and follicular carcinomas involving lesions with solid, trabecular, or scirrhous growth patterns (poorly differentiated carcinoma as designated by Sakamoto et al.) expressed maspin in significantly higher incidence than those with pure papillary or follicular patterns. Furthermore, 48.2% of anaplastic (undifferentiated) carcinomas diffusely expressed maspin, and the rest were completely negative. These findings indicate that, in contrast to other carcinomas, maspin expression is directly associated with the biological aggressiveness of thyroid carcinoma. Further studies regarding the function of maspin in this carcinoma are required.     

Hashimoto's thyroiditis is associated with papillary thyroid carcinoma: role of TSH and of treatment with L-thyroxine

The possible association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) is a still debated issue. We analyzed the frequency of PTC, TSH levels and thyroid autoantibodies (TAb) in 13?738 patients (9824 untreated and 3914 under l-thyroxine, l-T(4)). Patients with nodular-HT (n=1593) had high titer of TAb and/or hypothyroidism. Patients with nodular goiter (NG) were subdivided in TAb-NG (n=8812) with undetectable TAb and TAb+NG (n=3395) with positive TAb. Among untreated patients, those with nodular-HT showed higher frequency of PTC (9.4%) compared with both TAb-NG (6.4%; P=0.002) and TAb+NG (6.5%; P=0.009) and presented also higher serum TSH (median 1.30 vs 0.71?μU/ml, P<0.001 and 0.70?μU/ml, P<0.001 respectively). Independently of clinical diagnosis, patients with high titer of TAb showed a higher frequency of PTC (9.3%) compared to patients with low titer (6.8%, P<0.001) or negative TAb (6.3%, P<0.001) and presented also higher serum TSH (median 1.16 vs 0.75?μU/ml, P<0.001 and 0.72?μU/ml, P<0.001 respectively). PTC frequency was strongly related with serum TSH (odds ratio (OR)=1.111), slightly related with anti-thyroglobulin antibodies (OR=1.001), and unrelated with anti-thyroperoxidase antibodies. In the l-T(4)-treated group, when only patients with serum TSH levels below the median value (0.90?μU/ml) were considered, no significant difference in PTC frequency was found between nodular-HT, TAb-NG and TAb+NG. In conclusion, the frequency of PTC is significantly higher in nodular-HT than in NG and is associated with increased levels of serum TSH. Treatment with l-T(4) reduces TSH levels and decreases the occurrence of clinically detectable PTC.     

高迁移率蛋白A1和高迁移率蛋白A2在甲状腺乳头状癌中的表达及意义

目的 探讨高迁移率蛋白A1(HMGA1)和高迁移率蛋白A2(HMGA2)表达与甲状腺乳头状癌发生、发展及转移的关系.方法 收集新鲜和石蜡包埋的35例甲状腺乳头状癌(PTC)和相应的35例癌旁甲状腺组织(FT)及10例甲状腺良性病变旁正常组织(NT).采用实时荧光定量PCR及免疫组化法分别检测HMGA1和HMGA2 mRNA及蛋白的表达水平.结果 HMGA1和HMGA2 mRNA在NT组几乎都不表达,二者在PT组表达较NT组差异无统计学意义(P＞0.05),二者在PTC组表达为NT组的173.5倍和5.9倍(均P＜0.01).HMGA1和HMGA2蛋白分别在NT组、PT组及PTC组的表达水平逐步升高,组间比较有统计学意义(均P＜0.01);PTC组中HMGA1和HMGA2蛋白表达水平分别在临床分期和淋巴结有无转移比较中有统计学意义(P＜0.05或P＜0.01),分别与患者的年龄、肿瘤大小、性别比较差异均无统计学意义(P＞0.05).PTC组中HMGA1 mRNA和蛋白的表达水平都较HMGA2显著升高(P＜0.05或P＜0.01).结论 HMGA1和HMGA2过表达与PTC的发生、发展和转移有关.相对于HMGA2,HMGA1是鉴别甲状腺良恶性病变更好的分子指标.     

Pro12Ala substitution in peroxisome proliferator-activated receptorγ2 is associated with low adiponectin concentrations in young Japanese men

Peroxisome proliferator-activated receptor gamma (PPAR gamma) has been shown to play an important role in adipocyte differentiation. A Pro12Ala substitution in PPAR gamma 2 has been reported to decrease receptor activity in vitro and to be associated with a decreased risk of type 2 diabetes in the general population. Recently, a PPAR response element (PPRE) was identified in the adiponectin promoter, suggesting that decreased PPAR gamma activity may lead to lower adiponectin levels. In the present study, serum adiponectin concentrations and the PPAR gamma Pro12Ala polymorphism were analyzed to determine whether this polymorphism is associated with lower serum adiponectin concentrations in young healthy Japanese subjects. Serum adiponectin concentrations were significantly lower in men with than in those without the Ala12 allele, whereas body mass index (BMI), homeostasis model assessment (HOMA)-beta, HOMA-IR, the insulin sensitivity index during oral glucose tolerance test (ISI [composite]), and serum leptin did not differ significantly between subjects with and without the Ala12 allele. Stepwise regression demonstrated BMI and the Ala12 allele to be independent predictors of serum adiponectin concentrations in men. In conclusion, the Pro12Ala substitution in PPAR gamma 2 may reduce serum adiponectin concentrations in young Japanese men.     

Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age.

Papillary thyroid carcinoma (PTC) is a malignancy that has good prognosis especially among patients up to 45 years of age; about half of the patients are female and of childbearing age. Lymph node recurrence (LNR) occurs in 10%-14% of patients but is considered to be associated with relatively good prognosis. The purpose of this study was to estimate the association between patient age at primary operation, and the behavior of the disease after LNR. Between 1967 and 1994, 495 patients underwent surgery for primary PTC at the Department of Surgery, Helsinki University Central Hospital. There were 391 (79.0%) women and 104 (21.0%) men with a mean age of 44.5 years (range, 10.8-85.4 years). Fifty-eight patients in whom LNR was the first clinical sign of persistent disease after complete clinical response to primary treatment were included in this series. At the time of primary operation, 37 (64.3%) of the 58 patients who developed LNR were younger than 45 years of age and 21 patients were older. The mean times to LNR in these groups were 42.0 months (range, 3.0-194.5 months) and 49.0 months (range, 3.6-209.0 months) respectively. Carcinoma-specific 5-year survival after LNR was 100% (95% confidence interval [CI] 88.8%-100.0%) in patients ages up to 45 years and 61.1% (40.5%-82.8%) in older patients; 10-year survival rates were 100%, and 41.3% (p < 0.0001), respectively. Relative survival at 10 years was 98.6% for patients ages up to 45 years and 42.6% for older patients (p = 0.0014). Using the Cox model it was shown that development of LNR after primary treatment has an independent highly significant negative effect on survival (p < 0.001) in patients over 45 years of age. Prognosis of PTC even after LNR on patients ages up to 45 years at the time of the primary operation is almost parallel to the normal reference population, but in patients over 45 years of age the prognosis is relatively poor.