Snail1 expression in colorectal cancer and its correlation with clinical and pathological parameters.

BACKGROUND: Snail1 is a transcription regulator of E-cadherin. The loss of E-cadherin seems to be a crucial step in the process of Epithelial-mesenchymal transition (EMT). EMT initiates invasion and proliferation in many tumours. Overexpression of Snail1 is known to be associated with poor outcome in several solid tumours. The aim of this study was to analyse its expression profile and prognostic significance in colorectal cancer. METHODS: Tissue microarrays (TMA) containing paraffin-embedded primary colorectal cancer (CRC) tissue samples from 251 patients were used in this study. The expression of Snail1 and E-cadherin was assessed by immunohistochemistry in different tumour compartments, corresponding lymph node metastases and normal colonic mucosa. Intensity of staining was classified according to the Remmele score (standardized scoring system) as well as the semiquantitative score established by Blechschmidt et al. RESULTS: Snail1 expression was observed in 76% of the CRC. Loss of E-cadherin was noted in 87% of the CRC. Snail1 positive tumours were significantly correlated with Snail1 positive lymph node metastases (p=0.03). There was no significant correlation between loss of E-cadherin and Snail1 expression, or between N-stage or grading and Snail1 expression. Kaplan-Meier survival analysis identified no prognostic impact of Snail1 expression on overall survival. CONCLUSION: Snail1 expression was detectable in most of the CRC but showed no significant association with E-cadherin loss, clinical pathological characteristics or overall survival. The observed loss of E-cadherin could be explained by effects of other important EMT pathways, such as the Wnt-signalling cascade.

Intrahepatic endometriosis as differential diagnosis: case report and literature review.

Intrahepatic endometriosis is one of the rarest forms of atypical endometriosis; only eighteen cases have been reported in the English literature. We describe the case of a 32-year-old woman, who presented with persistent, non-cyclical upper right quadrant abdominal pain, a central liver cyst, and no history of endometriosis. Three years previous, she was diagnosed with an intrahepatic cyst. The lesion progressed and two laparoscopic deroofing-operations were performed, yet the diagnosis of intrahepatic endometriosis was never reached. She presented in our clinic with further progress of the cyst as well as obstruction of the intrahepatic biliary system. The magnetic resonance imaging showed a 9.5 cm × 12 cm, lobulated intrahepatic cyst. We performed an ultrasonic pericystectomy. Immunostaining confirmed intrahepatic endometriosis. Only one of the previously described eighteen patients with intrahepatic endometriosis presented with cyclical pain in the upper right abdominal quadrant accompanying menstruation. This lack of a "typical" clinic makes it challenging to diagnose extragonadal endometriosis without histopathology. A previous history of endometriosis was described in only twelve cases, thus the diagnosis of this condition should not be limited to patients with a known history of endometriosis. Six of 18 patients were postmenopausal, demonstrating this condition is not limited to women of reproductive age. A preoperative diagnosis was only reached in seven of the previously described cases, highlighting the importance of preoperative biopsies. Yet due to the potential adverse effects, a transhepatic biopsy must be discussed individually. Although rare, intrahepatic endometriosis should always be considered as a differential diagnosis in women with recurrent hepatic cysts, regardless of age or previous medical history. In such cases, histology is essential and a pericystectomy should be performed as standard of care.

Notch 1 tumor expression is lacking in highly proliferative pancreatic neuroendocrine tumors.

To date, very little is known about the development of benign organic hyperinsulinism and its metastatic potential. Typical morphologic, biochemical, or genetic differentiations for benign or malign tumor course of insulinomas do not exist. As signaling pathways may affect pancreatic cancer development and the maintenance of the neoplastic phenotype, the purpose of this study was to examine the role of Notch1 expression in organic hyperinsulinism. We examined 32 well-differentiated pancreatic endocrine tumors (wd PET); 11 wd PET of unknown behavior (wd PET ub); and 15 wd pancreatic endocrine cancer (wd PEC) for Notch1 expression by immunohistochemistry. Demographic data, clinical data, and follow-up of all patients were analyzed. Islets of the Langerhans show the strongest Notch1 staining in nearly 90 %. Positive Notch1 staining was absent in the acinar of the pancreas. In patients with a wd PET more than every second tumor (56.3 %/n = 18/32) demonstrated a negative Notch1 staining. The other 14 patients were positive for Notch1. Tumors of unknown behavior (wd PET ub) and malignant insulinomas had no signs of Notch expression in contrast to benign insulinomas. Considering the clinical and histomorphological tumor behavior, no correlation between Notch1 expression and clinical data was found. The missing Notch expression in the malignant tumor course might be used as a potential predictive marker, but further studies are needed to investigate the underlying molecular mechanism.

High EpCAM expression is linked to proliferation and lauren classification in gastric cancer.

BACKGROUND: The association of EpCAM expression with the progression of gastric cancer remains unclear. Here, we investigated the expression of EpCAM in gastric cancer subtypes and correlated the data to tumor cell proliferation and clinicopathologic factors. METHODS: The intratumoral expression of EpCAM was assessed in 163 primary gastric cancers (61 diffuse-, 62 intestinal-, 32 mixed-type and 8 unclassified tumors) by immunohistochemistry, using the monoclonal antibody Ber-EP4. Intensity of staining was classified according the HercepTest-score using a standardized scoring system. Ki-67 was used to examine the proliferation in tumor tissue. RESULTS: Strong EpCAM expression was observed in 77% of the tumors and in 85% of the corresponding lymph nodes. Of the primary tumors, 58% (n=74) presented a homogeneous intratumoral EpCAM expression while 42% were characterised by a heterogenous expression pattern. Tumors with high EpCAM expression at the invasive front were associated with significantly (p=0.03) higher proportion of lymph node metastases and lower median overall survival (p=0.001). Diffuse type tumors presented a significantly higher EpCAM expression at the invasion front compared with the tumor centre (p=0.036). Multivariate survival analysis identified high EpCAM expression at the invasive front as an independent prognostic factor.We observed a significant (p=0.001) correlation between high EpCAM expression and higher tumor cell proliferation. CONCLUSION: High EpCAM expression associates with proliferation and progression of gastric cancer, especially in the diffuse type. Considering the discontenting results of the current adjuvant concepts for gastric cancer patients, EpCAM might be target in the adjuvant therapy of this malignant disease.

Down-regulation of CDH1 is associated with expression of SNAI1 in colorectal adenomas.

INTRODUCTION: Down-regulation of E-cadherin (CDH1) and epithelial-mesenchymal transition (EMT) are considered critical events for invasion and metastasis of colorectal carcinoma. Here we tested whether the important regulators of E-cadherin expression SNAI1 and TWIST1 are already detectable in human colorectal adenomas. METHODS: RNA was extracted from a set of randomly selected formalin-fixed and paraffin-embedded (FFPE) colorectal adenomas (n = 41) and normal colon mucosa (n = 10). Subsequently mRNA expression of CDH1, CDH2, SNAI1 and TWIST1 was analysed by quantitative RT-PCR analysis. CDH1 as well as SNAI1 protein expression were assessed by immunohistochemistry (IHC). RESULTS: SNAI1 mRNA was expressed in 78% (n = 32/41), TWIST1 mRNA in 41% (n = 17/41) and CDH2 mRNA in 41% (n = 17/41) of the colorectal adenoma tissue, while normal colon mucosa was negative for these transcription factors. We found a significant correlation between reduced CDH1 and the presence of SNAI1 mRNA expression and for combined SNAI1 and TWIST1 mRNA expression, respectively. A correlation between CDH2 mRNA expression and reduced CDH1 expression was not observed. We confirmed the relationship between SNAI1 expression and reduced E-cadherin expression on the protein level via IHC. CONCLUSION: Our data show that SNAI1 and Twist1 are already expressed in benign precursor lesions of colorectal cancer and that SNAI1 expression was significantly correlated with lower expression of CDH1. Whether these findings reflect true EMT and/or are a sign of a more aggressive biology need to be investigated in further studies.