OBJECTIVES: To investigate the expression of apolipoprotein C1 (APOC1) in papillary thyroid carcinoma (PTC) and its effects on proliferation and apoptosis of PTC cells. METHODS: The expression level of APOC1 in PTC and its impact on prognosis were analyzed using GEPIA 2 and Kaplan-Meier databases. Immunohistochemistry (IHC) and Western blotting were used to detect the expression of APOC1 in PTC and adjacent tissues and in 3 PTC cell lines and normal thyroid Nthyori 3-1 cells. In TPC-1 and BCPAP cells, the effect of Lipofectamine 2000-mediated transfection with APOC1 siRNA or an APOC1-overexpressing plasmid on cell growth and colony formation ability were examined by observing the growth curves and using colony-forming assay. The changes in cell cycle and apoptosis of the transfected cells were analyzed with flow cytometry. RT-qPCR and Western blotting were used to detect the changes in expressions of P21, P27, CDK4, cyclin D1, Bcl-2, Bax, caspase-3 and caspase-9 and the key proteins in the JAK2/STAT3 signaling pathway. RESULTS: APOC1 expression was significantly higher in PTC tissues and the 3 PTC cell lines than in the adjacent tissues and Nthyori 3-1 cells, respectively. In TPC-1 and BCPAP cells, APOC1 knockdown obviously reduced cell proliferative activity, increased the percentage of G0/G1 phase cells, lowered the percentages of S and G2 phase cells, promoted cell apoptosis, and downregulated mRNA and protein expression levels of CDK4, cyclin D1 and Bcl-2 and the protein levels of p-JAK2 and p-STAT3. APOC1 overexpression in the cells produced the opposite effects on cell proliferation, apoptosis, cell cycle and the mRNA and protein expressions. The application of AG490, a JAK2 inhibitor, strongly attenuated APOC1 overexpression-induced activation of the JAK2/STAT3 signaling pathway in BCPAP cells. CONCLUSIONS APOC1 overexpression promotes proliferation and inhibits apoptosis of PTC cells possibly by activating the JAK2/STAT3 signaling pathway and accelerating cell cycle progression.
Humans ; Apoptosis ; Cell Proliferation ; STAT3 Transcription Factor/metabolism* ; Signal Transduction ; Janus Kinase 2/metabolism* ; Thyroid Neoplasms/pathology* ; Thyroid Cancer, Papillary ; Cell Line, Tumor ; Carcinoma, Papillary

Radioiodine ablation (RIA) therapy is one of the most important treatments for papillary thyroid carcinoma (PTC), but some patients who received (131)I have radioiodine-refractory disease caused by the decreased expression of the Na(+)/I(-) symporter (NIS). BRAF(V600E) mutation is one possible risk factor that can disturb the NIS expression, but the roles are unclear in clinical practice. This research discussed the association of BRAF(V600E) mutation and NIS expression in PTC tissue and the clinical implications in RIA therapy. 134 PTC samples were collected between June 2013 and June 2014 from Tongji Hospital affiliated to Tongji Medical College, and their clinical characteristics were analyzed. RT-PCR was used to detect the BRAF(V600E) mutation from formalin-fixed paraffin-embedded samples, and immunohistochemistry was applied to detect the NIS expression. IPP software was used to calculate the relative expression quantity of NIS. We found that there was no significant correlation between the absorbance (A) values of NIS and clinicopathologic features in these cases, even thyroid stimulating hormone. BRAF(V600E) mutation showed inhibitory effect on the NIS expression without statistically significant difference in all PTC cases (β=-0.0195, P=0.085), but in the subgroup without hashimoto's thyroiditis (HT), BRAF(V600E) mutation could significantly inhibit the NIS expression (β=-0.0257, P=0.046). The results indicate that BRAF(V600E) mutation is correlated with a lower expression of NIS in PTCs without HT, suggesting the radioiodine-refractory effects during RIA therapy in these patients.
Adult ; Carcinoma ; genetics ; metabolism ; Carcinoma, Papillary ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Proto-Oncogene Proteins B-raf ; genetics ; Symporters ; genetics ; metabolism ; Thyroid Neoplasms ; genetics ; metabolism

OBJECTIVETo investigate the association of concomitant BRAFV600E mutation with central lymph node metastases in papillary thyroid carcinoma (PTC).

METHODSThe clinicopathological data of 126 PTC patients who underwent surgical treatment within a period of 2 years were retrospectively analyzed. The BRAF V600E gene mutation was detected by quantitative fluorescence PCR.

RESULTSThe BRAF mutation rate was 69.0% (87/126). The univariate analysis showed that BRAF mutation status was significantly associated with central lymph node metastasis (P<0.05), while the gender, multiple lesions, tumor size, extra-thyroidal invasion, Hashimoto's thyroiditis and tumor stage were not significantly associated with the BRAF mutation (P>0.05 for all). The multivariate analysis showed that only central lymph node metastasis was significantly correlated with BRAF mutation (P<0.05). When the diameter of tumor was ≤10 mm, BRAF mutation was statistically not significantly correlated to central lymph node metastasis (P>0.05). When the diameter of tumor was >10 mm, the central lymph node metastasis rate was significantly higher in patients with positive BRAF mutation than that in patients with a negative BRAF mutation (P<0.05).

CONCLUSIONSThe presence of BRAF mutation is an independent predictive factor for central lymph node metastasis. When PTC is with preoperative positive BRAF mutation, the cervical dissection should be routinely performed. The larger the tumor diameter is, the more important is the central lymph node dissection. There should be re-evaluated the necessity of preventative central lymph node dissection when the tumor diameter was ≤5 mm in patients with negative BRAF mutation.

Carcinoma ; epidemiology ; genetics ; metabolism ; Carcinoma, Papillary ; Hashimoto Disease ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; diagnosis ; genetics ; Mutation ; Polymerase Chain Reaction ; Proto-Oncogene Proteins B-raf ; genetics ; Retrospective Studies ; Thyroid Neoplasms ; epidemiology ; genetics ; metabolism

OBJECTIVETo study the expression of EpCAM and E-cadherin in papillary thyroid carcinoma and to analyze its correlation with various clinicopathologic parameters.

METHODSImmunohistochemical study for EpCAM and E-cadherin was carried out in 91 cases of papillary thyroid carcinoma. Twenty-four cases of papillary hyperplasia of thyroid were used as controls.

RESULTSIn all of the 24 cases of papillary hyperplasia, EpCAM was located on the cell membrane, while in the 91 cases of papillary thyroid carcinoma studied, EpCAM was located within the cytoplasm, with 36.3% (33/91) showing nuclear localization as well. In all the papillary hyperplasia cases studied, E-cadherin showed membranous expression. E-cadherin expression was reduced in 84.6% (77/91) of papillary thyroid carcinoma, as compared with the surrounding native thyroid parenchyma. Amongst the 33 cases of papillary thyroid carcinoma which showed nuclear localization of EpCAM, 30 cases also showed reduced E-cadherin expression. There was a positive correlation between nuclear expression of EpCAM and loss of E-cadherin expression (P = 0.000; Spearman correlation coefficient = 0.857). Nuclear expression of EpCAM correlated with follicular variant of papillary thyroid carcinoma and presence of extrathyroidal extension ( P = 0.037 and 0.033, respectively). Loss of E-cadherin expression correlated with age of patients and presence of lymph node metastasis (P = 0.018 and 0.010, respectively).

CONCLUSIONSE-cadherin expression is reduced in papillary thyroid carcinoma, as compared with native thyroid parenchyma and papillary hyperplasia. Papillary thyroid carcinoma shows loss of EpCAM membranous expression and increased cytoplasmic/nuclear accumulation. Detection of these two markers may provide a valuable reference in defining the biologic behaviors of papillary thyroid carcinoma, including extrathyroidal extension and lymph node metastasis.

Antigens, Neoplasm ; metabolism ; Cadherins ; metabolism ; Carcinoma, Papillary ; metabolism ; secondary ; Cell Adhesion Molecules ; metabolism ; Cell Membrane ; metabolism ; Cytoplasm ; metabolism ; Epithelial Cell Adhesion Molecule ; Humans ; Lymphatic Metastasis ; Neoplasm Proteins ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology

The study aimed to verify the prognostic utility, therapeutic application and clinical benefits of tumor substaging and HER2 status in papillary non-muscle invasive bladder cancer (NMIBC). Select NMIBC transurethral resection specimens from 141 patients were used to construct tissue microarrays for assessing the substaging, HER2 protein expression by immunohistochemistry (HER2-IHC) and gene amplification by dual-color silver in situ hybridization (HER2-SISH). Substages were identified by the differing depth of tumor invasion (pTa / pT1a / pT1b / pT1c). HER2 protein expression was semiquantitatively analyzed and grouped into negative (score 0, 1+) and positive (score 2+, 3+). Other clinicopathological variables were also investigated. For NMIBC, HER2-IHC and HER2-SISH showed positive results in 6/141 (4.3%) and 4/141 (2.8%) respectively, which correlated well with tumor substaging. In multivariate analysis, substaging, HER2-IHC, and HER2-SISH were found to be independent predictors of progression-free survival (P < 0.001, P < 0.001, P = 0.031). HER2-IHC was the sole independent predictor of recurrent free survival in NMIBC (P = 0.017). It is suggested that tumor substaging and HER2 status are independent predictive markers for tumor progression or recurrence, and thus could be included in diagnostic and therapeutic management for NMIBC.
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Carcinoma, Papillary/*metabolism/*pathology ; Carcinoma, Transitional Cell/metabolism/pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/*metabolism ; Reproducibility of Results ; Sensitivity and Specificity ; Urinary Bladder Neoplasms/*metabolism/*pathology ; Young Adult

OBJECTIVETo investigate the relationship between ALDH1A1 expression and lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC).

METHODSOne hundred and fifty-three paraffin-embedded specimens of PTC treated in the Beijing Tongren Hospital of Capital Medical University were selected from January 2006 to December 2013. The expression of ALDH1A1 was detected in both tumor tissues and adjacent non-tumor tissues by immunohistochemistry and several clinicopathological parameters (size, bilaterality, multifocality, tumor border and extrathyroidal extensions) were assessed by HE staining. The correlation of ALDH1A1 expression with LNM was analyzed.

RESULTSIn 153 cases of PTC, there were 82 cases with LNM, 126 cases with high ALDH1A1 expression in tumor tissues, and 112 cases with high ALDH1A1 expression in adjacent non-tumor tissues. On univariate analysis, patient age < 45 years, tumor size of 10 mm or more, invasive tumor border, and high ALDH1A1 expression in tumor tissues predicted LNM in PTC (P < 0.05), whereas gender, bilaterality, multifocality, extra-thyroidal extensions and high ALDH1A1 expression in adjacent non-tumor border did not (P > 0.05). On multivariate analysis, invasive tumor border, high ALDH1A1 expression in tumor tissues were found to be independent predictive factors for LNM in PTC (P < 0.05). After a follow-up of 42 months (median time), four patients developed locoregional recurrences, but no distance recurrence or disease related death were seen in 82 patients of follow up. The estimated 5-year locoregional recurrence was 4.88%. Of these four logcoregional recurrences, three involved lymph nodes and one involved the remaining thyroid. The ALDH1A1 expression in tumor tissues was high in all of recurrence cases.

CONCLUSIONHigh ALDH1A1 expression in tumor tissues is correlated with lymph node metastasis in PTC and may be used as an independent predictive factor of LNM, and may improve treatment and follow-up strategies for PTC.

Aldehyde Dehydrogenase ; metabolism ; Carcinoma ; metabolism ; pathology ; Carcinoma, Papillary ; Humans ; Immunohistochemistry ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Risk Factors ; Thyroid Neoplasms ; metabolism ; pathology

OBJECTIVE: To investigate the expression and clinical significance of EphA2 and E cadherin proteins in papillary thyroid carcinoma tissues, and to explore the relationship between them. METHOD: Using immunohistochemical SP/PV method, we detected the expression of EphA2 and E cadherin in tumors of 43 papillary thyroid carcinomas, 11 thyroid adenoma and 10 normal thyroid tissues, then studied their relationships with clinic pathological factors. RESULT: The total positive rates of EphA2 and E cadherin expression were 58. 14% and 32. 56% in papillary thyroid carcinoma tissues, 18. 18% and 81. 81% in thyroid adenoma.tissues and they were 10. 00% and 100. 00% in normal thyroid tissues respectively. The positive expression of EphA2 in carcinoma tissues was higher than in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05) and the positive expression of E cadherin in carcinoma tissues was lower than that in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05). The positive expression of EphA2 and E cadherin was associated with lymph node metastasis and histological grade (P<0. 05), but it was not associated with all the clinic-pathological factors including age, sex and the tumor size (P>0. 05). In papillary thyroid carcinoma tissues, the expression of EphA2 was negatively correlated with the expression of E cadherin protein (r= -0. 416, P<0. 01). CONCLUSION EphA2 and E cadherin may be involved in carcinogenesis and development of papillary thyroid carcinoma.
Adenoma ; metabolism ; pathology ; Antigens, CD ; Cadherins ; metabolism ; Carcinoma ; metabolism ; pathology ; Carcinoma, Papillary ; Humans ; Lymphatic Metastasis ; Receptor, EphA2 ; metabolism ; Thyroid Cancer, Papillary ; Thyroid Gland ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology

Adenocarcinoma ; Carcinoma, Papillary ; Estrogens ; metabolism ; Humans ; Receptors, Estrogen ; metabolism ; Thyroid Neoplasms ; metabolism

OBJECTIVETo study the clinicopathological features, immunophenotype, differential diagnosis and prognosis of low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA).

METHODSThe histopathological features and clinical and pathological data of nine cases of LGNPPA were retrospectively analyzed. Immunohistochemistry (Two-step EnVision methods) was used to evaluate the expression of CKpan, vimentin, CK7, CK19, TTF-1 and TG; in situ hybridization was used to detect Epstein-Barr virus mRNA (EBER); and flow-through hybridization was used to evaluate the presence of human papilloma virus (HPV).

RESULTSThe mean age for the nine patients (eight males, one female) was 45.3 years (range 23 to 62 years). Microscopically the tumors were characterized by lobulated, papillary and glandular structures with patchy distribution of spindle cells. The papillary interstitial tissue was edematous, myxoid or hyalinized. The tumors were unencapsulated and infiltrated into the surrounding stroma. Four cases displayed transition between normal nasopharyngeal epithelium to neoplastic cells; and one case contained psammoma bodies. Five cases were strongly positive for CKpan, vimentin, CK7, CK19, TTF-1, and were focally positive for EMA and CD117. These five cases were all negative for TG, CK5/6, CK20, S-100 protein, p63, Calponin and SMA. In situ hybridization for EBER and flow-through hybridization for HPV were negative in all five cases. Follow-up data showed no post-operative recurrence of the LGNPPA.

CONCLUSIONSLGNPPA is a rare low-grade neoplasm with distinct morphological characteristics. Its diagnosis is primarily based on the site of lesions and the histological features. The diagnosis and differential diagnosis of LGNPPA could be aided by immunohistochemical staining. LGNPPA may originate from nasopharyngeal epithelium; and the prognosis is good with simple and complete resection.

Adenocarcinoma, Papillary ; metabolism ; pathology ; Adult ; Carcinoma ; Diagnosis, Differential ; Female ; Herpesvirus 4, Human ; genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Proteins ; metabolism ; Nuclear Proteins ; metabolism ; Prognosis ; RNA, Messenger ; metabolism ; Retrospective Studies ; S100 Proteins ; metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism ; Vimentin ; metabolism

Adenocarcinoma, Follicular ; classification ; metabolism ; pathology ; Adenoma ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; Carcinoma, Papillary ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Signal Transduction ; Thyroid Neoplasms ; classification ; metabolism ; pathology