Prognostic significance of pituitary tumour-transforming gene-binding factor (PBF) expression in papillary thyroid carcinoma.

BACKGROUND: Pituitary tumour-transforming gene (PTTG)-binding factor (PBF), originally known as PTTG1 interacting protein (PTTG1IP), has been found to be significantly increased in well-differentiated thyroid cancer and independently associated with early tumour recurrence. OBJECTIVE: To assess the prognostic significance of PBF expression in a large cohort of papillary thyroid carcinoma (PTC) patients with a long-term follow-up. DESIGN AND PATIENTS: Retrospective analysis of PBF expression in PTC cases at different stages and correlate it with various clinicopathological parameters and patient survival. Subjects included 153 patients who received a thyroid operation for PTC at Chang Gung Memorial Hospital between 1991 and 2000. All patients had a complete follow-up till the end of 2010. MEASUREMENTS: Immunohistochemical study for PBF expression on tissue sections from tumour specimens. Bond automated machine (Leica Microsystems, Germany) with a polyclonal rabbit anti-PBF antibody (LifeSpan BioSciences, LS-C118942, Seattle, WA, USA) was used. SPSS 13.0 for Windows (SPSS Inc, Chicago, IL, USA) was used for all statistical analyses. RESULTS: High PBF expression was significantly correlated with age (P = 0·0298), distant metastases at diagnosis (P = 0·0139), tumour multicentricity (P = 0·0035), TNM stage (P = 0·0103), locoregional recurrence (P = 0·0410) and disease-specific mortality (P = 0·0064). The expression level of PBF was significantly correlated with disease-specific survival (P = 0·0065). Cox regression analysis showed that age, tumour size and PBF expression were independent prognostic indicators (P = 0·0097, P = 0·0021 and P = 0·0179). CONCLUSION: PBF expression may be a promising biomarker for prognostic and therapeutic purpose. More large-scale studies are needed to clarify its potential usefulness.

Prognostic significance of Tiam1 expression in papillary thyroid carcinoma.

T lymphoma and metastasis gene 1 (Tiam1) is a guanine nucleotide exchange factor (GNEF) that regulates the guanosine triphosphatase to facilitate the exchange of guanosine diphosphate for guanosine triphosphate. It specifically activates Rac1, a member of the Rho family of GTPases. Tiam1 is involved in cell proliferation, cytoskeletal organization, cellular adhesion, and transcriptional activation. It has been suggested that alterations in Tiam1 expression might contribute to the progression of various human cancers. The usefulness of Tiam1 expression as a prognostic marker in papillary thyroid carcinoma (PTC) has not been investigated yet. The aim of this study was to analyze the expression of Tiam1 in PTC as well as its association with the clinicopathologic features and prognostic significance. Surgical tissue samples were taken from 106 PTC patients who had been followed up for at least 9.3 years. Strong expression of Tiam1 was detected in 54% of the cases. Tiam1 expression was associated significantly with various clinicopathologic parameters, such as gender (P=0.039), tumor multicentricity (P=0.0124), histologic subtype (P=0.0427), TNM stage (P=0.0151), and distant metastases at diagnosis (P=0.0001). Survival analysis showed that the Tiam1 low-expression group had a significantly shorter overall survival time than Tiam1 high-expression group (P=0.0007). Multivariate analysis showed that Tiam1 expression was a significant and independent prognostic indicator (P=0.0090) for PTC patients. Tiam1 expression may be a novel and independent prognostic marker of PTC patients.

Expression pattern and prognostic significance of claudins 1, 4, and 7 in nasopharyngeal carcinoma.

Claudins are major tight junction proteins that regulate the integrity and function of tight junctions. Aberrant expression of claudins has been shown in various carcinomas with diverse prognostic implications. However, their expression pattern and prognostic value have not been investigated in nasopharyngeal carcinoma. This is the first study to characterize the expression pattern of claudins 1, 4, and 7 in a cohort of 176 patients with nasopharyngeal carcinoma and a minimum follow-up of 9.4 years. Immunohistochemistry with semiquantitative assessment of expression of claudins 1, 4, and 7 was performed on 176 biopsy specimens. Results were correlated with sex, age, extent of tumor, lymph node status, the presence or absence of distant metastasis, and patient survival. High expression of claudins 1 and 4 (72.2% and 88.1%) and low expression of claudin 7 (82.4%) were frequently detected. Low claudin 4 expression (P = .020) and high claudin 7 expression (P < .001) were associated with distant metastasis. Elevated claudin 7 expression also correlated with high tumor stage (P = .001). Furthermore, decreased claudin 4 expression (P = .003) and increased claudin 7 expression (P < .001) independently predicted shorter distant metastasis-free survival by Cox regression analysis. Claudin 4 and claudin 7 may be a novel biomarker for the prediction of distant metastasis and unfavorable prognosis in nasopharyngeal carcinoma.

Expression of caspase-3-dependent apoptosis in mural thrombi leukocytes.

Failure of arteriovenous access is mostly due to graft thrombosis and multifactorial, with medical and surgical etiologies. Apoptosis of blood cells, such as macrophages, lymphocytes and eosinophils, may play an important role in thrombus formation. We also investigated caspase-3-dependent apoptosis in thrombi. We recorded clinical parameters in 43 consecutive patients with vascular access failure (13 men, 30 women; mean age+/-SD, 64.6+/-14.2 years) who underwent surgical thrombectomy. Major presentations included absent (92%) and/or near near-absent (16%) flow through the access during hemodialysis. Cardiovascular risk factors were hypertension (70%), hyperlipidemia (47%), diabetes mellitus (47%), chronic obstructive pulmonary disease (12%), heart failure (12%), coronary artery disease (21%), and stroke (16%). Laboratory data included hemoglobin level of 100+/-17 g/L, total white blood cell count of 7.65+/-2.14 x 10(9)/L, and platelet count of 205.6+/-57.9 1000/ìL. Abnormal biochemistry data included elevated blood urea nitrogen level of 63.5+/-24.4 mg/dL and creatinine level of 8.6+/-4.0 mg/dL (normal <1.4 mg/dL). Thrombi were characterized by apoptosis (32%) in a caspase-dependent pathway in all types of leukocytes. Thrombi in arteriovenous access failure demonstrate apoptosis by means of the caspase-3 pathway in white blood cells.

Caspase-3-dependent apoptosis in cardiac myxoma: not associated with human papillomavirus or Epstein-Barr virus.

Cardiac myxoma is the most common tumor of the heart, has a variable clinical presentation and immunohistochemical profile. Viral infections, such as herpes simplex virus, human papillomavirus (HPV), and Epstein-Barr virus (EBV), may play an important role in the causes of cardiac myxoma. This investigation will demonstrate caspase-3-dependent apoptosis in cardiac myxoma without HPV or EBV infection. This study included 15 patients with cardiac myxoma, who were treated with surgical excision of the lesion. Data were collected on detailed clinical parameters. Terminal deoxynucleotidyl transferase nick-end labeling assay, electrophoresis, and caspase-3 immunohistochemical studies were performed to characterize apoptosis. Genechip containing 39 subtypes was used to elucidate HPV; and polymerase chain reaction to detect LMP-1 gene of EBV. The patient population comprised of eight (53%) women and seven (47%) men. The mean age of patient participants was 45 years, with an age range of 30-70 years. All patient cases were sporadic myxomas rather than familial myxomas. The patient presentations included dyspnea (53%), asymptomatic (27%), stroke (7%), chest pain (7%), and fever (7%). All lesions were located in the left atrium. The individual patient cases of myxoma did not differ in location or clinical event in terms of pathological scores, such as vascular proliferation, inflammation, cellularity, hyaline, calcification, or thrombosis. Cardiac myxoma is characterized by apoptosis through caspase-dependent pathway. HPV or EBV was not detected in any of the study patient samples. In conclusion, no viral genomes of HPV or EBV were detected in these 15 patients. This study demonstrates that caspase-3-dependent apoptosis in cardiac myxoma is not dependent on concurrence of previous HPV and/or EBV infection.