Association of BRAF V600E Mutant Allele Proportion with the Dissemination Stage of Papillary Thyroid Cancer.

The early identification of aggressive forms of cancer is of high importance in treating papillary thyroid cancer (PTC). Disease dissemination is a major factor influencing patient survival. Mutation status of BRAF oncogene, BRAF V600E, is proposed to be an indicator of disease recurrence; however, its influence on PTC dissemination has not been deciphered. This study aimed to explore the association of the frequency of BRAF V600E alleles in PTC with disease dissemination. In this study, 173 PTC samples were analyzed, measuring the proportion of BRAF V600E alleles by qPCR, which was then normalized against the proportion of tumor cells. Semiquantitative analysis of BRAF V600E mutant protein was performed by immunohistochemistry. The BRAF V600E mutation was present in 60% of samples, while the normalized frequency of mutated BRAF alleles ranged from 1.55% to 92.06%. There was no significant association between the presence and/or proportion of the BRAF V600E mutation with the degree of PTC dissemination. However, the presence of the BRAF mutation was significantly linked with angioinvasion. This study's results suggest that there is a heterogeneous distribution of the BRAF mutation and the presence of oligoclonal forms of PTC. It is likely that the BRAF mutation alone does not significantly contribute to PTC aggressiveness.

E-cadherin and NEDD9 expression in primary colorectal cancer, metastatic lymph nodes and liver metastases.

In Croatia, colorectal cancer mortality rates in males are the third highest in Europe, after Hungary and Slovakia. The results for females rank Croatia in second place after Hungary. According to previous studies, the loss of E-cadherin expression and the higher expression of neural precursor cell-expressed developmentally downregulated 9 (NEDD9) are associated with a worse prognosis. The aim of the present study was to analyze the immunohistochemical expression of NEDD9 and E-cadherin as markers of metastatic potential using a tissue microarray. This retrospective study included 40 previously untreated patients, including 23 males and 17 females with a median age of 64.5 years (range 38-84), with colorectal cancer and synchronous liver metastases that underwent simultaneous colorectal and hepatic resection between January 1st 2006 and December 31st 2013, in the Clinical Hospital Center Sestre Milosrdnice (Zagreb, Croatia). The most frequent tumor stage was T3, while the most frequent nodal stage was N1. Microvascular invasion was present in 37.5% of patients, while perineural invasion was observed in 30% of patients. The immunohistochemical staining index of E-cadherin was highly positive in 87.5% samples of colorectal cancer, 67.7% of lymph nodes and 77.5% of liver metastases. In the primary tumor, highly positive NEDD9 expression was identified in 22.5% of patients. In lymph nodes, it was identified in 35.5% of patients, while in the liver, it was identified in 30% of patients. Significant positive correlations were observed between the percentage of positive lymph nodes and the immunohistochemical staining index of E-cadherin (ρ=0.372; P=0.039) and NEDD9 (ρ=0.451; P=0.011) in lymph nodes. After the conclusion of the study, 55% of the patients succumbed. No significant differences in survival rates were identified regarding the expression of E-cadherin and NEDD9 in the primary tumor, metastatic lymph nodes and liver metastases. Due to the small sample size and the negative results obtained, further research is required to implement these parameters as prognostic factors.

Immunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC).

Extensive research is being conducted to identify novel diagnostic, predictive and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC), as only a few markers have been routinely used so far with limited success. Our aim was to assess the expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), E-cadherin, and γ-catenin in PDAC in relation to clinicopathological parameters and patient survival. We also investigated if there is a correlation of NEDD9 expression with E-cadherin or γ-catenin. The protein expression was determined by immunohistochemistry in 61 PDAC and 61 samples of normal pancreatic tissue. The log rank test and Kaplan-Meier survival curve were used for survival analysis. E-cadherin and γ-catenin expressions were reduced in PDAC, and completely retained in normal pancreatic tissue. Expression of NEDD9 was significantly increased in PDAC (strong expression in 78.7% of cases and moderate in 21.3%) and reduced in normal pancreatic tissue (strong positivity in 45.9% of cases, moderate in 31.1%, and weak in 23%). There was a positive correlation between reduced E-cadherin and γ-catenin expression in PDAC (p = 0.015). The loss or reduced expression of E-cadherin had a negative impact on patient survival (p = 0.020). A negative correlation between E-cadherin expression and tumor grade was also observed (p = 0.011). Decreased E-cadherin expression was more common in male patients with PDAC (81.3% vs. 60% for females, p = 0.005). γ-catenin and NEDD9 expressions were not statistically correlated with tumor stage and grade, gender, nor with patient survival. Our results support the role of NEDD9, E-cadherin and γ-catenin proteins in PDAC, but further research should clarify in detail their mechanism of action in pancreatic cancer.

Gender Difference in Distribution of Estrogen and Androgen Receptors in Intestinal-type Gastric Cancer.

BACKGROUND: Gender difference in survival of patients with gastric cancer is not well investigated. The aim of this study was to analyze the gender-related distribution of estrogen receptor alpha (ERα) and androgen receptor (AR) in the epithelium and stroma of intestinal-type gastric cancer. MATERIALS AND METHODS: Immunohistochemical analysis was performed in 60 patients (42% females). RESULTS: In gastric cancer patients, frequency of ERα-positive cells was lower in epithelium than in healthy individuals, but not significantly. In stroma and epithelium, AR-positive cells were absent from samples of women with T1 and T2 stage disease, while in men, their frequency was significantly increased in stroma of those with T3 and T4 stages and was significantly higher compared to women. AR-positive cells in stroma were fibroblasts, myofibroblasts and mast cells. CONCLUSION: To our knowledge, this study is the first to show gender differences in the distribution and frequency of AR-positive cells in neoplastic stroma of gastric cancer.

Age and sex differences in genome damage between prepubertal and adult mice after exposure to ionising radiation.

The mechanisms that lead to sex and age differences in biological responses to exposure to ionising radiation and related health risks have still not been investigated to a satisfactory extent. The significance of sex hormones in the aetiology of radiogenic cancer types requires a better understanding of the mechanisms involved, especially during organism development. The aim of this study was to show age and sex differences in genome damage between prepubertal and adult mice after single exposure to gamma radiation. Genome damage was measured 24 h, 48 h, and 72 h after exposure of 3-week and 12-week old BALB/CJ mice to 8 Gy of gamma radiation using an in vivo micronucleus assay. There was a significantly higher genome damage in prepubertal than in adult animals of both sexes for all sampling times. Irradiation caused a higher frequency of micronuclei in males of both age groups. Our study confirms sex differences in the susceptibility to effects of ionising radiation in mice and is the first to show that such a difference occurs already at prepubertal age.

Estrogen and androgen receptors in inflammatory fibroid polyp (Vanek's tumor): case report.

BACKGROUND/AIM: Vanek's tumor is an inflammatory fibroid polyp (IFP) of very low incidence, which originates in the submucosa of the stomach, duodenum, jejunum and ileum. The etiology of this tumor is still unknown. Histologically, IFP is characterized by submucosal spindle cell proliferation in fibromyxoid stroma with inflammatory infiltrate. The aim of the present study was to investigate the presence of estrogen and androgen receptors in IFP and compare it with its proliferative loci. PATIENTS AND METHODS: The study analyzed a 79-year-old patient suffering from IFP. Analyses were performed by immunohistochemistry. RESULTS: Androgen-positive spindle cells were detected at the periphery of onion skin-like formations. Estrogen receptor-positive cells were not detected and Ki67 showed low proliferative activity. CONCLUSION: This case report shows for the first time the presence of androgen receptor-positive cells whose location corresponds with the distribution of Ki67-positive cells in IFP.

Expression of growth hormone receptor, plakoglobin and NEDD9 protein in association with tumour progression and metastasis in human breast cancer.

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related deaths among female population worldwide. Metastases are the common cause of morbidity and mortality in breast cancer and can remain latent for several years after surgical removal of the primary tumour. Thus, the identification and functional characterisation of molecular factors that promote oncogenic signalling in mammary tumour development and progression could provide new entry points for designing targeted therapeutic strategies for metastatic breast cancer. In the present study, we investigated the expression of proteins involved in cell signalling (growth hormone receptor (GHR) and NEDD9) and cell-cell adhesion (plakoglobin) in epithelial and stromal compartments of primary ductal invasive breast carcinomas and their axillary lymph node metastases versus non-metastatic tumours. Obtained data revealed remarkable increase in the expression levels of GHR and NEDD9 proteins in both epithelial and stromal components of axillary lymph node metastases in comparison with those of non-metastatic tumours, suggesting that the expression of these two proteins may provide biomarkers for tumour aggressiveness.

Frequency of tuberculosis at autopsies in a large hospital in Zagreb, Croatia: a 10-year retrospective study.

AIM: To assess the frequency and forms of pulmonary tuberculosis at autopsy in a high-traffic hospital in the capital city of a country with a low tuberculosis incidence. METHODS: We performed a retrospective search of autopsy data from the period 2000 to 2009 at Sestre Milosrdnice University Hospital Center, Zagreb, Croatia. We also examined patients' records and histological slides. RESULTS: Of 3479 autopsies, we identified 61 tuberculosis cases, corresponding to a frequency of 1.8%. Active tuberculosis was found in 33 cases (54%), 23 of which (70%) were male. Of the 33 active cases, 25 (76%) were clinically unrecognized and 19 (76%) of these were male. CONCLUSION: Clinically undiagnosed tuberculosis accounted for a substantial proportion of active tuberculosis cases diagnosed at autopsy. Autopsy data may be an important complement to epidemiological data on tuberculosis frequency.

[Clinicopathological characteristics of micropapillary variant of urinary bladder carcinoma]. / Klinicko-patoloska obiljezja mikropapilarne varijante urotelnog karcinoma mokracnog mjehura.

Micropapillary urothelial carcinoma (MUC) is a rare variant of urinary bladder carcinoma associated with highly aggressive behaviour. The aim of this study was to analyse clinicopathological features of MUC particularly a relationship between pathological stage at presentation and proportion of micropapillary component (MPC) in 10 patients with MUC. In the examined period (January 1st 2004 - June 30th, 2007) there were 610 patients with urinary bladder cancer (M:F = 456:154), while 10 (1.6%) of them were patients with MUC. All MUC were invasive at the time of diagnosis. Stage distribution at presentation was 4 T1(40%) and 6 T2 (60%) and the percentage of MPC correlated with pathological stage: 3 of 4 (75%) tumors staged T1 had less than 10% of MPC and 5 of 6 (83,3%) tumors staged T2 had more than 50% of MPC. MUC is an aggressive tumor, often in advanced stage of disease at the time of diagnosis, in which the pathological stage is related to the proportion of MPC.