MRI纹理联合Cripto-1与SOX2蛋白对甲状腺乳头状癌颈部淋巴结转移的诊断价值

目的:分析磁共振成像（MRI）T2加权成像（T2WI）纹理联合Cripto-1与SOX2蛋白在甲状腺乳头状癌（PTC）颈部淋巴结转移（LNM）中的诊断价值。方法:选择82例PTC患者,并留取患者根治术标本进行后期免疫组化研究。根据入选患者病理诊断结果,将42例LNM阳性者分为观察组,40例LNM阴性者分为对照组。分析MRI纹理参数联合Cripto-1与SOX2蛋白诊断PTC伴LNM的敏感度、特异度及符合率的临床价值。结果:Cripto-1蛋白在伴LNM的PTC中的阳性表达显著强于未伴LNM的PTC中的阳性表达（P<0.05）。Cripto-1蛋白免疫组化染色阳性表达多位于肿瘤周围组织,表现为棕黄色颗粒,主要位于细胞膜上,且Cripto-1蛋白在伴LNM的PTC中染色强度显著强于未伴LNM的PTC。SOX2蛋白在伴LNM的PTC中的阳性表达显著强于未伴LNM的PTC中的阳性表达（P<0.05）。SOX2蛋白免疫组化染色阳性表达多位于肿瘤周围组织,表现为棕黄色颗粒,主要位于细胞核上,且SOX2蛋白在伴LNM的PTC中染色强度显著强于未伴LNM的PTC。两组T2WI图像纹理分析的熵、角二阶矩以及相关间具有统计学意义（P<0.05）,而逆差矩、偏度、对比、峰度以及均值间均无统计学意义（P>0.05）。预测PTC伴LNM的熵、角二阶矩以及相关对应AUC分别为0.884、0.783、0.718,敏感度分别为97.13%、79.42%、44.14%,特异度分别为70.00%、60.00%、90.00%。MRI纹理参数对PTC伴LNM的诊断价值稍优于Cripto-1蛋白,差异无统计学意义（P＞0.05）;而MRI纹理参数联合Cripto-1与SOX2蛋白诊断在敏感度、特异度及符合率方面均显著优于单独诊断（P<0.05）。结论:MRI纹理联合Cripto-1与SOX2蛋白诊断PTC伴LNM的敏感度、特异度及符合率均高于单独MRI纹理参数或Cripto-1蛋白的检查。此外,其有望为PTC患者预后及其治疗决策提供更可靠、准确的依据。     

Overexpression of c-Met protein in human thyroid tumors correlated with lymph node metastasis and clinicopathologic stage.

To examine the expression of c-Met protein in thyroid tumors and the correlation of c-MET protein expression with lymph node metastasis (LNM) and pathological stage, 111 papillary thyroid carcinomas (PTC), including 44 with synchronous LNM, and 117 follicular adenomas (FA) were immunohistochemically examined using dewaxed sections of formalin-fixed, paraffin-embedded tissues. Immunohistochemical results were confirmed by Western blot analysis. For PTC, positive immunostaining was observed in 107 of 111 (96.4%) cases and was diffusely present in either cytoplasm and nucleus, or only cytoplasm or only nucleus of cancer cells at varying intensities. Staining tended to be stronger in the periphery of cancer cell nests. Positive reaction was also found in 44 of 117 (37.6%) cases of FA. However, the extent and intensity of c-Met immunostaining in FA were far less than those in PTC (p < 0.0001). Forty-four PTC cases (39.6%) exhibited LNM, and the extent and intensity of c-Met expression were significantly correlated with both LNM (p < 0.0001) and pathological stage (p < 0.0001). No significant correlation of c-Met expression with age, sex or tumor size was found. Our findings suggest that PTC expresses c-Met protein much more strongly and intensively than does FA, and that strong and intense overexpression of c-Met protein may be an indicator of the presence of lymph node metastasis and advanced pathological stage of papillary thyroid carcinoma.     

EGFR and CXCR1 expression in thyroid carcinoma in Qassim Region-Saudi Arabia: Correlation with clinicopathological parameters

AimsRecent evidence indicates an increased incidence of thyroid carcinoma, especially papillary thyroid carcinoma (PTC), in Saudi Arabia. EGFR and CXCR1 were reported to have increased expression in several human neoplasms. The goals of the present research was to investigate EGFR and CXCR1 expression in thyroid carcinoma and correlate the results to the established prognostic factors.MethodsImmunohistochemical study for both EGFR and CXCR1 was performed on formalin-fixed paraffin-embedded thyroid carcinomas tissues sections applying Labeled Streptavidin-biotin method (LSAB).ResultsRemarkable high expression of EGFR and CXCR1 were observed in PTC cases (56% and 63% respectively). There was association between EGFR expression in PTC and each of histologic subtype, lymph node metastasis (LNM), distant metastasis (DM), TNM staging and tumor relapse. There was statistical significant correlation between CXCR1 expression in PTC and each of histologic subtype, LNM, and tumor relapse. A significant correlation was detected between concomitant EGFR and CXCR expression and LNM, DM, increasing stage and tumor relapse.ConclusionsThe results of the present study demonstrated, a statistically positive correlation of EGFR and CXCR1 expression in PTC compared to normal thyroid tissues and nodular hyperplasia in Qassim Region- Saudi Arabia. Concomitant high expression of both receptors were strongly correlated with LNM, DM, TNM stage and tumor relapse than did each alone. These findings suggest that EGFR and CXCR1 play crucial roles in PTC and serve as predictors of poor prognosis, biomarkers of tumor diagnosis, and potential targets of cancer therapeutics.     

Expression of X-linked inhibitor of apoptosis protein in neoplastic thyroid disorder

X-linked inhibitor of apoptosis protein (XIAP) is associated with tumor genesis, growth, progression and metastasis, and acts by blocking caspase-mediated apoptosis. In the present study, we sought to evaluate the expression patterns of XIAP in various neoplastic thyroid disorders and determine the association between XIAP expression and clinicopathologic factors. Expression of XIAP was evaluated with immunohistochemical staining using monoclonal anti-XIAP in 164 specimens of conventional papillary thyroid carcinoma (PTC) and 53 specimens of other malignant or benign thyroid tumors. XIAP positivity was observed in 128 (78%) of the 164 conventional PTC specimens. Positive rates of XIAP expression in follicular variant PTC, follicular, medullary, poorly differentiated, and anaplastic thyroid carcinoma specimens were 20%, 25%, 38%, 67%, and 38%, respectively. Six nodular hyperplasia specimens were negative and 1 of 7 follicular adenomas (8%) was positive for XIAP. Lateral neck lymph node metastases were more frequent in patients negative for XIAP expression (P = 0.01). Immunohistochemical staining for XIAP as a novel molecular marker may thus be helpful in the differential diagnosis of thyroid cancer. Moreover, high XIAP expression in conventional PTC is strongly associated with reduced risk of lateral neck lymph node metastasis.     

High expression of GPER1, EGFR and CXCR1 is associated with lymph node metastasis in papillary thyroid carcinoma

Clinical and epidemiological studies have shown that estrogen may be involved in the development and progression of papillary thyroid carcinoma (PTC). G protein-coupled estrogen receptor 1 (GPER1) is a novel seven-transmembrane estrogen receptor that functions alongside traditional nuclear estrogen receptors (ERs) to regulate the cellular responses to estrogen. The purpose of this study was to examine GPER1, EGFR and CXCR1 expression in PTC and to assess the association of their expression with clinicopathological indicators. GPER1, EGFR and CXCR1 protein expression in 129 PTCs, 61 nodular hyperplasia and 118 normal thyroid tissue specimens were analyzed using immunohistochemistry. The protein expression levels of these three molecules were up-regulated in PTCs. High protein expression of GPER1, EGFR and CXCR1 was significantly correlated with lymph node metastasis (LNM) (P ≤ 0.001). Furthermore, GPER1, EGFR and CXCR1 protein expression were correlated with one another. Concomitant high expression of these molecules had stronger correlation with LNM than did each alone (P = 0.002 for GPER1/EGFR, P = 0.013 for GPER1/CXCR1, P = 0.018 for EGFR/CXCR1 and P < 0.001 for GPER1/EGFR/CXCR1). Additionally, GPER1, EGFR and CXCR1 mRNA expression was assessed in 30 PTCs, 10 nodular hyperplasia and 10 normal thyroid tissue specimens using real-time RT-PCR. GPER1, EGFR and CXCR1 mRNA expression levels were up-regulated in PTCs, and high mRNA expression of GPER1, EGFR and CXCR1 was significantly correlated with LNM (P < 0.001 for all these three molecules). These results demonstrated that the evaluation of GPER1, EGFR and CXCR1 expression in PTC may be useful in predicting the risk of LNM.     

Thyroid stimulating hormone levels and BRAFV600E mutation contribute to pathophysiology of papillary thyroid carcinoma: Relation to outcomes?

AimsThe aim of this study was to evaluate the relation between the level of thyroid stimulating hormone (TSH) and progression of papillary thyroid carcinoma (PTC) with or without BRAF^V600E mutation.MethodsThe medical records and laboratory data of 547 patients with PTC and 94 patients with follicular adenoma (FA) were collected. The relationship between hormones levels and such end-points as extrathyroid extension (ETE), lymphovascular invasion (LVI) and lymph node metastasis (LNM) was assessed. In addition, age, gender, BRAF^V600E mutation status, histological type and Hashimoto’s thyroiditis (HT) were considered.Key findingsMost of the patients with PTC had hormones levels within the normal range, however, serum TSH concentration was significantly higher in PTC comparing with FA (P = 0.022). High levels of TSH in PTC were more frequent among women rather than men (P = 0.03) due to the gender differences in coexisting HT rate (P = 0.003). In contrast, LNM rate was higher in men (P = 0.0014). Coexisting HT significantly decreased the risk of ETE (OR = 0.67; 95%CI 0.44–1.00; P = 0.05) and LNM (OR = 0.59; 95%CI 0.37?0.94; P = 0.028) among males with PTC. However, there was no significant relationship between HT and PTC-related ETE and LNM in females. BRAF^V600E mutation was associated with presence of lymphocytic infiltration (P < 0.001) but not with HT (P = 0.08) and violation of thyroid function.ConclusionThe present study showed the lack of significant relationship between TSH levels and PTC aggressiveness (LNM, TNM stage, BRAF^V600E mutation). Higher TSH levels were found in patients with coexisting HT that was associated with female sex and multifocality of PTC.     

Thyroid Cancers with Benign-Looking Sonographic Features Have Different Lymph Node Metastatic Risk and Histologic Subtypes According to Nodule Size

A decision to perform fine needle aspiration (FNA) on thyroid nodules mainly depends on sonographic features. We investigated if lymph node metastasis (LNM) risk differed by tumor size of thyroid cancers without suspicious sonographic features. Three hundred sixty patients with thyroid cancers with benign looking sonographic features were grouped by nodule size on ultrasonography (US) (≤ or >1 cm). The clinicopathologic parameters were compared between the groups. A multivariate analysis was performed to discover the independent factors predicting the presence of LNM. The nodules greater than 10 mm on US (n?=?157) demonstrated a larger tumor size on histology (17.9?±?14.5 vs. 5.6?±?2.4 mm, P?P?P?P?=?0.007). A multivariate analysis revealed that classical PTC, extrathyroidal extension, and the US nodule size >10 mm were independent predictive factors of LNM after adjusting for age, sex, TSH level, and multifocality. Thyroid cancers larger than 10 mm with benign US features are more likely to be nonclassical PTC than those with smaller diameters. The larger ones also have an increased risk of LNM in classical PTC. These cases require a more aggressive approach to FNA.     

EGFR、COX-2及P63蛋白表达与甲状腺乳头状癌侵袭转移的关系

目的　探讨甲状腺乳头状癌 (PTC)中表皮生长因子受体 (EGFR)、环氧化酶 2 (COX 2 )和 p6 3蛋白的表达与肿瘤侵袭转移的关系。方法　采用免疫组化S P法检测 6 7例PTC(其中腺内侵袭 4 1例、腺外侵袭 2 6例 ;有淋巴结转移 2 9例、无淋巴结转移 38例 )、3例滤泡癌和 15例甲状腺腺瘤中EGFR、COX 2及 p6 3蛋白的表达。结果　EGFR、COX 2和 p6 3蛋白在PTC组织中的阳性表达率分别为 88 1%、82 1%和 70 2 % ,均显著高于甲状腺腺瘤 (P <0 0 5 ) ;EGFR与COX 2、COX 2与p6 3蛋白在PTC组织中的的表达呈明显正相关 (P <0 0 5 ) ;EGFR和COX 2在PTC腺外侵袭组和有淋巴结转移组阳性表达率均明显高于腺内侵袭组和无淋巴结转移组 (P <0 0 5 ) ,p6 3蛋白阳性表达率与淋巴结转移有关 (P <0 0 5 )、与浸润程度无关。结论　EGFR与COX 2在PTC组织中的高表达可能促进肿瘤的侵袭和转移 ,p6 3蛋白在PTC的高表达提示其与PTC的细胞增殖相关     

Expression of osteopontin messenger RNA by macrophages in ovarian serous papillary cystadenocarcinoma: a possible association with calcification of psammoma bodies

Calcified psammoma bodies often appear in human ovarian serous papillary cystadenocarcinoma. Osteocalcin (OC), osteonectin (ON) and osteopontin (OPN) are three members of non-collagenous bone-related proteins known to be related with mineralization of bone. To clarify possible involvement of these bone matrix proteins in the calcification of the psammoma bodies, the expression of OC, ON and OPN was analyzed by immunohistochemical and in situ hybridization studies using 15 surgical specimens. OPN protein was detected in the calcified area of the psammoma bodies which was positively stained by von Kóssa's staining, while OC and ON proteins were not. OPN protein was not detected in any cells in tissues, but OPN messenger ribonucleic acid (mRNA) was detected in CD68-positive macrophages, indicating that OPN was produced and promptly secreted by macrophages. These results suggest that OPN produced and promptly secreted by macrophages and subsequently translocated to psammoma bodies may be causally related with the calcium phosphate deposition in the psammoma bodies of the ovarian serous papillary cystadenocarcinomas.     

三叶因子3在甲状腺乳头状癌中的表达及临床意义

目的 探讨甲状腺乳头状癌（PTC）患者血清与组织中三叶因子3(TFF3)的表达水平及意义。方法 收集甲状腺肿瘤患者153例,其中乳头状癌组66例、腺瘤组51例、乳头状增生组36例,正常组153例（来源于每例标本的正常甲状腺组织）。16例正常人血清标本作为ELISA检测的
正常组。采用免疫组织化学SP法和原位杂交技术检测甲状腺手术标本中TFF3蛋白和mRNA的表达;ELISA检测血清TFF3浓度。结果 1. TFF3蛋白和mRNA均表达于细胞质,呈棕黄色颗粒。66例乳头状癌TFF3表达阳性率92.42％;36例乳头状增生阳性率47.22%;51例腺瘤阳性率31.37％;正
常组阳性率25.40%;各组TFF3 mRNA阳性率略低于其蛋白,且与蛋白表达呈正相关（P.<0.0001）;甲状腺癌组积分吸光度显著高于其他3组（P<0.01）; 2. 甲状腺乳头状癌中TFF3及mRNA高表达率与TNM分期和淋巴结转移有关（P<0.01）; 3. 甲状腺癌组血清TFF3浓度明显高于乳头
状增生组、腺瘤组和健康对照组（P<0.001）。血清TFF3浓度在甲状腺癌组织阳性组明显高于阴性组（P<0.05）。结论 甲状腺乳头状癌高表达 TFF3蛋白及mRNA,检测血清TFF3浓度可能成为诊断甲状腺乳头状癌的筛选指标。     

Overexpression of epidermal growth factor receptor and its downstream effector,focal adhesion kinase,correlates with papillary thyroid carcinoma progression

Epidermal growth factor receptor (EGFR) and its downstream effector, focal adhesion kinase (FAK), have been shown to be overexpressed frequently in human malignancies and implicated in tumour aggressiveness. We aimed to investigate the relationship between EGFR and FAK expression and their possible correlation with the clinical phenotype of patients with papillary thyroid carcinoma (PTC). Expression profiles of EGFR and FAK were analysed in PTC tissue samples (n = 104) by immunohistochemistry and Western blotting. Additionally, EGFR and FAK were immunohistochemically analysed in 20 primary tumours paired with their metastatic tissue in lymph nodes. High expression of EGFR and FAK was found in 55.77% and 57.69% cases, respectively, with a strong positive association between them (P < 0.0001, Spearman's correlation coefficient = 0.844). Expression of each molecule and their coexpression correlated significantly with the presence of lymph node metastasis (LNM), degree of tumour infiltration, extrathyroid invasion and pT status of the patients. Western blot analysis confirmed that coexpression of high levels of EGFR and FAK correlated with adverse clinicopathological features. When compared to the corresponding primary tumour, increased or maintained high levels of EGFR and FAK were found in LNM, indicating their concordant expression during lymphatic spread. In conclusion, high levels of EGFR and its downstream effector, FAK, in association with lymphatic spread and tumour infiltration indicate their involvement in PTC progression and suggest that both molecules may predict its aggressive behaviour. Furthermore, FAK could be a potential target for anticancer therapy in patients with advanced thyroid cancer.     

Cyclooxygenase-2 and inducible nitric oxide synthase expression in thyroid neoplasms and their clinicopathological correlation

To evaluate the expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in thyroid neoplasms in a Korean population, we studied a total of 154 cases: papillary carcinoma of classical type (PTC), 86; follicular adenoma (FA), 21; follicular carcinoma (FC), 35; medullary carcinoma (MC), 3; undifferentiated carcinoma (UC), 5; and Hurthle cell neoplasm (HN), 4. Using immunohistochemical staining, COX-2 expression was detected in 62 (72.1%) PTC specimens, 5 (23.8%) FA specimens, 10 (28.6%) FC specimens, 0 (0.0%) MC specimens, 1 (20.0%) UC specimen, and 3 (75%) HN specimens. iNOS expression was detected in 66 (76.7%) PTC specimens, 4 (19.0%) FA specimens, 13 (37.1%) FC specimens, 0 (0.0%) MC specimens, 3 (60.0%) UC specimens, and 4 (100%) HN specimens. The results showed that COX-2 and iNOS were frequently expressed in the PTC and HN specimens, and iNOS was more frequently overexpressed in the FC specimens than in the FA specimens. In PTC, COX-2 and iNOS were significantly overexpressed in patients over 45 yr of age (p=0.029, p=0.041), and iNOS expression was increased in patients with a large primary tumor (p=0.028). These results suggest that the upregulation of COX-2 and iNOS may contribute to the tumor progression of thyroid gland, particularly in PTC and HN, and iNOS may play an adjuvant role during the tumor progression of FC.     

Serum vascular endothelial growth factor-D levels correlate with cervical lymph node metastases in papillary thyroid carcinoma

The aim of this multicenter study was to evaluate the clinical relevance of serum vascular endothelial growth factor-D (VEGF-D) in papillary thyroid carcinoma (PTC). This prospective study consisted of 74 patients with primary PTC and 15 patients with benign thyroid nodules treated from 2008 to 2009. VEGF-D concentration was compared with patient clinicopathologic features and lymph node metastases. There was no significant difference in mean serum VEGF-D levels between the PTC and benign thyroid nodule groups. Within the PTC group, serum VEGF-D levels were significantly higher in patients with lymph node metastases than in patients without metastases (241.92 vs. 213.89 pg/ml, respectively; P = 0.035). Receiver operating characteristic curve analysis revealed that preoperative serum VEGF-D levels were predictive of lymph node metastases in the patients >45 years. Serum VEGF-D level that was correlated with the presence of cervical lymph node metastases in PTC patients might be a useful prognostic indicator.     

Serum vascular endothelial growth factor-D levels correlate with cervical lymph node metastases in papillary thyroid carcinoma

The aim of this multicenter study was to evaluate the clinical relevance of serum vascular endothelial growth factor-D (VEGF-D) in papillary thyroid carcinoma (PTC). This prospective study consisted of 74 patients with primary PTC and 15 patients with benign thyroid nodules treated from 2008 to 2009. VEGF-D concentration was compared with patient clinicopathologic features and lymph node metastases. There was no significant difference in mean serum VEGF-D levels between the PTC and benign thyroid nodule groups. Within the PTC group, serum VEGF-D levels were significantly higher in patients with lymph node metastases than in patients without metastases (241.92 vs. 213.89?pg/ml, respectively; P?=?0.035). Receiver operating characteristic curve analysis revealed that preoperative serum VEGF-D levels were predictive of lymph node metastases in the patients >45 years. Serum VEGF-D level that was correlated with the presence of cervical lymph node metastases in PTC patients might be a useful prognostic indicator.     

Papillary thyroid carcinoma with bone formation

Bone formation is a rarely encountered finding during histological examination of papillary thyroid carcinoma (PTC). This study aimed to analyze clinicopathological parameters in patients with PTC showing bone formation, to document histological features of bone formation in PTC, and to investigate osteogenic proteins. Bone morphogenic protein (BMP)-9 is known as the most potent osteoinductive protein of the BMP subtypes. Recent research suggests that the activin receptor-like kinase (ALK) 1 is an essential cellular receptor that mediates BMP-9-induced osteogenic signaling. A retrospective review of tumor sections from 567 patients with a diagnosis of PTC was performed. Using immunohistochemistry and quantitative real-time polymerase chain reaction, we investigated the expression of ALK1 and BMP-9 in normal thyroid tissue and PTC samples with and without bone formation. Bone formation was found in 13% of patients with PTC. A significant association was seen between bone formation and old age. BMP-9 expression in tumors was increased compared to that in normal thyroid tissues. BMP-9 expression in tumors with bone formation was not significantly different from that in tumors without bone formation. ALK1 expression in tumors with bone formation was increased compared to that in normal thyroid tissue and tumors without bone formation. Our study suggests that upregulation of ALK1 might be an underlying molecular mechanism that explains osteogenesis in PTC.     

Clinical importance of vascular endothelial growth factor (VEGF) for papillary thyroid carcinomas

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and may be produced by some cancer cells. Several recent reports have documented that increased expression of VEGF is associated with risk of recurrence or decreased recurrence-free survival in papillary thyroid cancers (PTC). The aims of this study were to determine whether immunohistochemical expression of VEGF is related to local and distant recurrence of PTC and to evaluate the relationship between hypervascularization and VEGF expression in papillary thyroid carcinomas. VEGF expression was examined immunohistochemically in 48 papillary carcinomas. Ten normal thyroids were used as controls. Patients were followed for 61.7 (range 24-143) months. Twelve of the patients had local and distant recurrences. VEGF immunostaining, blinded for clinicopathological data, was evaluated semiquantitatively by two pathologists. The difference between the recurrent (n:12) and nonrecurrent (n:36) carcinomas was statistically significant (p:0.001). VEGF expression was also stronger in papillary thyroid carcinomas than in normal thyroid tissues. The mean microvascular densities were significantly higher than in normal thyroid tissues. These data indicate that VEGF staining is strongly associated with increased frequency of local and distant recurrence in PTC and that the immunohistochemical profile of the expression may be used as a marker for predicting which tumors have metastatic potential.     

Follicular epithelial dysplasia of the thyroid: morphological and immunohistochemical characterization of a putative preneoplastic lesion to papillary thyroid carcinoma in chronic lymphocytic thyroiditis

In chronic lymphocytic thyroiditis (CLT), the follicular epithelial cells display cytological atypia resembling papillary thyroid carcinoma (PTC), and epidemiological studies have suggested an increased risk of PTC in patients with this condition. While reactive atypia is observed diffusely in CLT-affected thyroid parenchyma, it is not unusual to find microscopic foci morphologically distinct from the surrounding parenchyma, exhibiting more pronounced cytological and architectural atypia. These small atypical lesions, which we term “follicular epithelial dysplasia” (FED), are particularly prominent in cases of severe CLT, yet lack invasive growth, papillary architecture, or intranuclear pseudoinclusions. To gain further insight into their biological significance, we constructed a tissue microarray of 70 cases of CLT, comprised of morphologically normal thyroid, thyroid with reactive atypia, FED, follicular nodular disease (nodular hyperplasia or follicular adenoma), and PTC. Immunohistochemical staining was performed for a marker panel including PTC (HBME-1, cytokeratin 19, galectin-3, and cyclin-D1) as well as TTF-1, thyroglobulin, and p63. Slides were digitally scanned and immunohistochemical staining evaluated using automated image analysis software. FED lesions were positive for TTF-1 and thyroglobulin (50/50, 100 %), though some (13/50, 26 %) also expressed p63. Similar to PTC, strong diffuse staining was observed for HBME-1 (43/50, 86 %), cytokeratin 19 (48/50, 96 %), galectin-3 (20/50, 40 %) and cyclin-D1 (38/50, 76 %). In contrast, normal thyroid, reactive atypia, and follicular nodular disease were negative, or at most, exhibited focal weak staining for HBME-1, cytokeratin 19, and galectin-3. The results of this study demonstrate the presence of atypical microscopic lesions in CLT with an immunohistochemical profile similar to PTC, supporting the concept of a premalignant lesion preceding PTC, arising in the context of severe chronic inflammation.     

Hashimoto's thyroiditis shares features with early papillary thyroid carcinoma

Neoplastic transformation is a multistep process that results in a continuous spectrum from the normal (physiological) state to a fully established neoplasm. The gold standard for diagnosis of papillary thyroid carcinoma is conventional histology, the essential element being the characteristic nuclear features, regardless of whether papillary structures are present or not. However, other criteria are being used increasingly in the diagnosis of neoplasms, including immunohistochemical staining and molecular profile. The RET/PTC gene rearrangement is highly specific for papillary thyroid carcinoma and is associated with the characteristic nuclear features seen in papillary thyroid carcinoma. There is an overlap in the morphological features, immunohistochemical staining pattern, and most importantly, molecular profile between papillary thyroid carcinoma and Hashimoto's thyroiditis. Although considered a 'benign' condition, Hashimoto's thyroiditis almost always harbours a genetic rearrangement that is strongly associated with and is highly specific for papillary thyroid carcinoma. Submicroscopic foci of papillary thyroid carcinoma must be present in Hashimoto's thyroiditis, although the clinical behaviour is still benign. Further studies are required to predict which foci will progress to papillary thyroid carcinoma.