Risk factors of distant metastasis in the follicular variant of papillary thyroid carcinoma.

BACKGROUND/PURPOSE: The follicular variant of papillary thyroid carcinoma (FVPTC) is the most common variant of papillary thyroid carcinoma (PTC). A previous population-based study revealed its clinical behavior as a mix of classic papillary thyroid carcinoma (C-PTC) and follicular thyroid carcinoma. Whereas locoregional extension was lower in FVPTC than in C-PTC, the distant metastasis rate was higher in FVPTC than in C-PTC. The aim of this study was to evaluate the risk factors of distant metastasis in FVPTC postoperatively. METHODS: A retrospective review of 359 patients with final pathological diagnosis of FVPTC treated at Chang Gung Memorial Hospital between January 2000 and January 2014 was performed. After excluding patients who had inadequate pathological data for analysis or did not attend regular follow up for >1 year, 346 patients were included in this study. Univariate and multivariate statistical analyses were performed to determine the significance of various factors. RESULTS: Of the 346 patients with FVPTC, 19 (5.5%) had lymph node metastases and 32 (9.2%) had distant metastases. Two positive and one negative risk factors were predictive for distant metastasis using multivariate analysis: angiolymphatic invasion [odds ratio (OR), 3.085; 95% confidence interval (CI), 1.008-9.442], extrathyroidal extension (OR, 3.929; 95% CI, 1.330-11.602), and encapsulation (OR, 0.361; 95% CI, 0.154-0.850). CONCLUSION: The presence of angiolymphatic invasion, extrathyroidal extension, or nonencapsulation was associated with distant metastasis in FVPTC in this study. In FVPTC patients, postoperative investigation for distant metastasis may be warranted by the presence of these two positive risk factors or the absence of the one negative risk factor.

Overexpression of caldesmon is associated with lymph node metastasis and poorer prognosis in patients with oral cavity squamous cell carcinoma.

BACKGROUND: A previous comparative tissue proteomics study by the authors of the current study led to the identification of caldesmon (CaD) as one of the proteins associated with cervical metastasis of oral cavity squamous cell carcinoma (OSCC). In the current investigation, the authors focused on the potential functions of CaD in patients with OSCC. METHODS: CaD expression was examined in tissue samples from 155 patients using immunohistochemical analysis. The expression of CaD variants was determined by Western blot analysis and reverse transcriptase-polymerase chain reaction. In addition, the specific effects of CaD gene overexpression and silence were determined in OSCC cell lines. RESULTS: CaD expression was found to be significantly higher in tumor cells from metastatic lymph nodes compared with primary tumor cells, and was nearly absent in normal oral epithelia. Higher CaD expression was found to be correlated with positive N classification, poor differentiation, perineural invasion, and tumor depth (P = .001, P = .029, P = .001, and P = .031, respectively). In survival analyses, OSCC patients with higher CaD expression were found to have poorer prognosis with regard to disease-specific survival and disease-free survival (P = .003 and P = .014, respectively). Multivariate analyses further indicated that higher CaD expression was an independent predictor of disease-specific survival (P = .043). Serum CaD levels were found to be significantly higher in patients with OSCC, but this finding was not associated with clinicopathological manifestations. Data obtained from in vitro suppression, rescue, and overexpression of CaD in OEC-M1 cells indicated that CaD promotes migration and invasive processes in OSCC cells. CONCLUSIONS: The findings of the current study collectively suggest that the low-molecular-weight CaD expression in OSCC tumors is associated with tumor metastasis and patient survival.

Therapeutic outcome and prognosis in young patients with papillary and follicular thyroid cancer.

BACKGROUND: Papillary and follicular thyroid cancer is a common malignancy in young patients, and the incidence of this cancer has been increasing. The aims of this study are to assess the clinical characteristics of papillary and follicular thyroid cancer in young patients and evaluate the long-term therapeutic outcomes and prognostic factors for cancer mortality and recurrence. METHODS: We performed a retrospective analysis of 116 patients aged ≤20 years who underwent thyroidectomy and a mean follow-up of 11.1 ± 0.6 years. RESULTS: There were 28 (24.1%) patients classified into the residual cancer or relapse groups. The progression-free survival rate for the young patients was lower than that of the patients between 20 and 45 years of age; however, the difference between the thyroid cancer survival rates was not statistically different. Two of the 28 patients died of thyroid cancer. Thirteen patients who showed relapsed underwent (131)I whole-body scan; 6 of the 13 patients were diagnosed with distant metastases to the lung and 1 was diagnosed with distant metastases to the bones. Among the young patients, the 5- and 10-year progression-free survival rates were 79.1 and 73.4%, respectively, and the corresponding cancer survival rates were 99.1, and 96.5%, respectively. CONCLUSION: The progression-free survival in young patients with papillary and follicular thyroid cancer was lower than the patients of age 20-45 years; otherwise, cancer survival was higher than age group over or equal to 45 years.

Therapeutic outcomes of papillary thyroid cancer patients in different risk groups.

OBJECTIVE: The objective of this study was to determine the therapeutic outcome of papillary thyroid cancer (PTC) patients in different risk groups in one institute. METHODS: A total of 1,759 PTC patients were categorized into low- (n = 1,123), intermediate- (n = 75), and high-risk (n = 561) groups according to tumor-node-metastasis (TNM) stage. RESULTS: Of the patients, 15.1% presented with lymph node metastases, and 4.6% presented with distant metastases at the time of thyroid operation. After 8.0 ± 0.1 years of follow-up, 73 (4.2%) patients died of thyroid cancer. Tumor size, local invasion, and lymph node metastases adversely influenced recurrence and survival. Of the patients in the 3 groups, 9 (0.8%), 8 (10.7%), and 56 (10.0%) died of thyroid cancer, respectively. In addition, 88 (7.8%), 14 (18.7%), and 144 (25.8%) patients showed recurrence during the follow-up period. Patients with highly aggressive histological patterns showed increased recurrence and cancer mortality compared with the low-risk group; otherwise, values were not higher than those of the high-risk group. CONCLUSIONS: The cancer-related mortality was nearly 10% in the intermediate- and high-risk groups, and the patients in these groups required aggressive surgical and postoperative adjuvant therapies.

Therapeutic outcomes of papillary thyroid carcinomas with tumors more advanced than T1N0M0.

PURPOSE: This retrospective study analyzed the role of total or near-total thyroidectomy and adjuvant radioactive iodide ((131)I) 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 (131)I, 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 (131)I 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 (131)I 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 (131)I 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 (131)I treatments, most patients with persistent or recurrent local-regional neck cancer were free of relapse; the cancer mortality rate was 19.0%.

Overexpression of BST2 is associated with nodal metastasis and poorer prognosis in oral cavity cancer.

OBJECTIVES/HYPOTHESIS: Bone marrow stromal cell antigen 2 (BST2) was one of the proteins that were found to be related to tumor metastasis in our previous proteomic study. Now we examine its clinical role on the oral cavity squamous cell carcinoma (OSCC). STUDY DESIGN: Individual retrospective cohort study and basic research. METHODS: Immunohistochemical analysis, Western blotting, and quantitative real-time polymerase chain reaction were used to demonstrate the expression levels of BST2 on 159 OSCC tumors. RNA interference was utilized for cell migration and proliferation study in vitro. RESULTS: BST2 expression was significantly higher in OSCC cells of metastatic lymph nodes and primary tumor cells, compared to adjacent normal epithelia. Higher BST2 expression was associated with positive N stage, advanced overall stage, perineural invasion, and tumor depth (P = .049, .015, .021, and .010, respectively). OSCC patients with higher BST2 expression had poorer prognosis for disease-specific and disease-free survival (P = .009 and .001, respectively). Multivariate analyses also demonstrated that higher BST2 expression is an independent prognostic factor of disease-specific and disease-free survival (P = .047 and .013, respectively). In vitro suppression of BST2 expression in OEC-M1 cells showed that BST2 contributes to tumor migration of OSCC cells. CONCLUSIONS: The findings in this study indicate that BST2 expression in OSCC tumors is an independent prognostic factor of patient survival and associated with tumor metastasis.

Heterogeneous ribonucleoprotein K and thymidine phosphorylase are independent prognostic and therapeutic markers for oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the major cancer of head and neck with increasing incidence and mortality in Taiwan. We investigate hnRNP K, TP and FLIP expression and assess the prognostic and therapeutic potential of these markers in oral squamous cell carcinoma (OSCC). We analyzed hnRNP K, TP, and FLIP expression in 110 OSCC patients by immunohistochemistry. Statistical analyses were applied to correlate nuclear and cytoplasmic hnRNP K with elevated TP and FLIP, and to determine the associations of these three markers with clinicopathological manifestations, and assess their prognostic and therapeutic significance. The therapeutic implication of elevated TP was determined by measuring the sensitivity of OSCC cells to the TP-targeting drug, 5-fluoro-5'-deoxyuridine (5'-DFUR). We found that each of these proteins was overexpressed in OSCC tumors. Nuclear hnRNP K and cytoplasmic hnRNP K were strongly associated with TP (r(2)=0.344, P=0.0004) and FLIP (r(2)=0.201, P=0.035), respectively. High hnRNP K and TP levels were associated with clinicopathological parameters predictive of poorer treatment outcome. Multivariate analyses indicated that cytoplasmic hnRNP K and TP are independent predictors of overall survival (P=0.022 and 0.009, respectively) and disease-free survival (P=0.012 and 0.005, respectively). OSCC cells expressing high levels of TP were more sensitive to treatment with 5'-DFUR. Elevated cytoplasmic hnRNP K and TP overexpression are associated with poorer survival in OSCC patients. In vitro experiments suggest that OSCC tumors with high levels of TP are more sensitive to 5'-DFUR treatment. Thus, cytoplasmic hnRNP K and TP may be potential prognostic and therapeutic markers for OSCC.

Well-differentiated thyroid carcinoma with concomitant Hashimoto's thyroiditis present with less aggressive clinical stage and low recurrence.

Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are the most common differentiated thyroid cancers. Previous studies report that Hashimoto's thyroiditis (HT) concomitant with PTC is unusual and improves prognosis compared to classical PTC. Few previous studies address FTC concomitant with HT. In this study, we retrospectively analyzed data from one institution and compared clinical presentations and results of treatment of PTC and FTC with and without HT. In addition, studies comparing presentation and long term follow-up prognosis in classical PTC and FTC were conducted. A total of 1,788 PTC patients and 209 FTC patients underwent thyroidectomy with or without lymph node dissection and follow-up at Chang Gung Medical Center in Linkou, Taiwan. All thyroid carcinomas were pathologically classified according to World Health Organization criteria. Histological patterns of PTC were categorized as classical PTC, or PTC with HT. Follicular thyroid carcinoma patients were categorized as FTC or FTC with HT. The dataset contained a total of 1,703 PTC cases categorized as classical PTC, 85 cases of PTC with HT, 201 cases of FTC and eight cases of FTC with HT. Analysis of Classification of Malignant Tumors (TNM) stage revealed a higher percentage of classical PTC in stage IV than HT group (12.03% vs. 4.70%). Mean tumor size of classical PTC was larger than HT group. Although 42.3% of FTC cases presented with distant metastases, no cases of FTC with HT presented with distant metastasis. Cancer-specific mortality was higher in classical PTC group than in PTC with HT. There was 53.2% of FTC without HT assigned recurrent status, and six of them died of thyroid cancer. No cancer mortality or recurrence in HT with FTC. PTC and FTC with HT presented with better clinical stage and better prognosis after same therapeutic modality. In conclusions, both PTC and FTC with HT have less aggressive clinical presentation and better prognosis.