CDX2 downregulation is associated with poor differentiation and MMR deficiency in colon cancer.

BACKGROUND: Homeobox genes are often deregulated in cancer and can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. CDX2 has been implicated in differentiation, proliferation, cell adhesion, and migration. In this study, we investigated CDX2 mRNA and protein expression in relation to the clinicopathological characteristics of colon cancer, including mismatch repair status and recurrence risk. METHODS: Tumor samples were obtained from colon cancer patients. Biopsies from tumor tissue and normal adjacent tissue were fixed in liquid nitrogen for RNA extraction or in formalin and paraffin embedded (FFPE) for immunohistochemical staining. CDX2 mRNA expression was evaluated by RT-qPCR. FFPE sections were stained for MLH1, MSH2, MSH6, PMS2, and CDX2. RESULTS: A total of 191 patient samples were included in the study and analyzed by immunohistochemistry. Of these samples, 97 were further evaluated by RT-qPCR. There was no significant difference in CDX2 mRNA expression between tumor and normal tissues. CDX2 mRNA expression was significantly lower in right-sided tumors (p<0.05), poorly differentiated tumors (p<0.05), and MMR-deficient tumors (p<0.05). Similarly, CDX2 protein expression was more often low or absent in right-sided tumors (p<0.01), poorly differentiated tumors (p<0.001), and MMR-deficient tumors (p<0.001). Low CDX2 protein or mRNA expression was not associated with recurrence risk. CONCLUSION: We found that CDX2 downregulation is associated with MMR deficiency, right-sided tumors, and poor differentiation at both the mRNA and protein level. Whether CDX2 plays an active role in tumor progression in MSI/MMR-deficient tumors remains to be elucidated.

The clinical perspectives of CDX2 expression in colorectal cancer: a qualitative systematic review.

INTRODUCTION: Homeobox genes are often deregulated in cancer. They can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. It is implicated in differentiation, proliferation, cell-adhesion, and migration. CDX2 has been proposed as a tumor suppressor in colorectal cancer but its role is still controversial. This systematic review were undertaken in order to clarify CDX2s role in colorectal cancer. METHODS: A literature search was performed in the MEDLINE database from 1966 to February 2014. Only studies in which all or a part of the experimental design were performed on human colorectal cancer tissue were included. Thus, studies solely performed in cell-lines or animal models were excluded. RESULTS: Fifty-two articles of relevance were identified. CDX2 expression was rarely lost in colorectal cancers, however the expression pattern may often be heterogeneous within the tumor and can be selectively down regulated at the invasive front and in tumor buddings. Loss of CDX2 expression is probably correlated to tumor grade, stage, right-sided tumor location, MMR-deficiency, CIMP, and BRAF mutations. The CDX2 gene is rarely mutated but the locus harboring the gene is often amplified and may suggest CDX2 as a linage-survival oncogene. CDX2 might be implicated in cell proliferation and migration through cross-talk with the Wnt-signaling pathway, tumor-stroma proteins, and inflammatory cytokines. CONCLUSION: A clear role for CDX2 expression in colorectal cancer remains to be elucidated, and it might differ in relation to the underlying molecular pathways leading to the cancer formation.

Ventilatory pattern and associated episodic hypoxaemia in the late postoperative period in the general surgical ward.

Episodic oxygen desaturation is frequent in the late postoperative period and seems most pronounced on the second and third postoperative nights. However, the ventilatory pattern has not been described systematically during this period. We studied the ventilatory pattern and associated arterial oxygenation using the Edentrace II equipment (impedance pneumography and pulse oximetry) on the second and third postoperative nights in 28 patients undergoing major abdominal surgery. Ventilatory disturbances were common and included periods of hypopnoea, and obstructive, central and mixed apnoeas. Overall, the median (range) respiratory disturbance index (apnoeas + hypopnoeas per h) was 12 (0-121), with the patients spending 6% (0-65%) of the night in some kind of ventilatory disturbance. It was not possible from pre-operative snoring habits to predict patients who developed postoperative ventilatory disturbances. Overall, 23% (0-100) of the hypopnoeas and 7% (0-100) of the apnoeas were associated with episodic hypoxaemia. In conclusion, ventilatory disturbances were common in the late postoperative period in the general surgical ward and often associated with episodes of oxygen desaturation.

Smoking and alcohol abuse are major risk factors for anastomotic leakage in colorectal surgery.

BACKGROUND: Several studies have examined the association between anastomotic leakage and intraoperative risk factors in colorectal surgery, but only a few have taken patients' lifestyle into account. The aim of this study was to assess the association between anastomotic leakage and lifestyle factors such as smoking habits and alcohol consumption. METHODS: Between January 1993 and October 1996, 333 unselected consecutive patients in one surgical department underwent colonic or rectal resection with anastomosis. The association between clinical anastomotic leakage and 24 variables related to patient history, diagnosis and surgery was assessed retrospectively and analysed by logistic regression. RESULTS: The rate of clinical anastomotic leakage was 15.9 per cent (53 of 333 patients). Multiple regression analysis showed that smokers, compared with non-smokers, had an increased risk of anastomotic leakage (relative risk (RR) 3.18 (95 per cent confidence interval (c. i.) 1.44-7.00)), as did alcohol abusers compared with abstainers (RR 7.18 (95 per cent c.i. 1.20-43.01)). In the analysis, well known risk factors for anastomotic leakage such as site of anastomosis, age and stage of training of the surgeon were taken into account. CONCLUSION: Smoking and alcohol abuse are important predictive factors for anastomotic leakage after colonic and rectal resection.

'Clam' ileocystoplasty.

'Clam' enterocystoplasty has been performed in 23 patients in the treatment of lower urinary tract dysfunction. Twenty patients had neurogenic disorder while three were neurologically normal. Patients were evaluated urodynamically pre- and postoperatively. A significant change from a high pressure bladder to a low pressure bladder was found. Most patients had detrusor instability/hyperreflexia but 7 were operated due to poor bladder compliance. Only 2 patients had postoperative detrusor instability. Three patients later had a urinary diversion. Nineteen patients became dry giving a total success rate of 87% although 14 had to do clean intermittent self catheterization.

Successful pregnancy after ileocystoplasty. Case report.

A 32-year-old woman with multiple sclerosis had an uncomplicated pregnancy and labour two years after successful "clam" ileocystoplasty for urge incontinence and frequency of micturition. She remained well after three years following.

[Ileocystoplasty in the treatment of lower urinary tract dysfunction in patients with congenital myelomeningocele]. / Ileocystoplastik i behandlingen af nedre urinvejsdysfunktion hos patienter med kongenit myelomeningocele.

The therapeutic results in eight patients with congenital myelomeningocele and neuromuscular dysfunction of the lower urinary tract are presented. Urodynamic assessment was performed preoperatively and post-operatively. Ileocystoplasty was performed on all of the patients. The postoperative results were good in seven out of eight patients in whom urodynamic assessment reveals a low-pressure reservoir which functions well. All of the patients employ clean intermittent self catheterization and, employing this treatment, they are continent with stable renal function.

Localization of urokinase-type plasminogen activator in stromal cells in adenocarcinomas of the colon in humans.

Human colon adenocarcinomas and adjacent normal colon tissues were stained immunohistochemically with three different monoclonal antibodies and one preparation of polyclonal antibodies against each of the two plasminogen activators, uPA (urokinase type) and tPA (tissue type). The staining patterns seen with the respective sets of antibodies were identical. In all of 10 cases, staining for uPA in the normal colon tissue was confined to scattered fibroblastlike cells in the lamina propria. Other cells, including epithelial and endothelial cells, were uPA negative. All the tumor infiltrates contained many more uPA-positive cells than the normal tissues, but the staining was confined to fibroblastlike cells and endothelial cells in the tumor stroma, while no staining of the malignant epithelial cells was detected. Analysis for uPA by enzyme-linked immunosorbent assay (ELISA) in four cases showed an average uPA content of 0.15 ng uPA/mg protein in the normal colon tissues and 1.6 ng uPA/mg protein in the tumors. Tissue-type plasminogen activator immunoreactivity was confined to endothelial cells in both the normal colon tissue and in the colon carcinomas. These findings may indicate that colon cancer cells recruit stromal cells to produce uPA involved in degradation of the extracellular matrix during invasive growth.

Urokinase-type plasminogen activator in endothelial cells during acute inflammation of the appendix.

Urokinase and tissue-type plasminogen activators (u-PA and t-PA) were identified immunohistochemically in normal and inflamed human appendices by means of polyclonal and monoclonal antibodies. In addition, extracts of the tissues were analyzed for u-PA and t-PA by ELISA. Twelve appendices (five normal and seven with acute inflammation) were analyzed. In the normal appendices, there was a strong staining of the endothelial cells for t-PA, whereas there was negative staining for u-PA. In contrast, the endothelial cells in the inflamed appendices showed u-PA immunoreactivity, and negative or very weak reactions for t-PA. In the inflamed appendix, there was also a labeling of u-PA in fibroblast-like cells and in interstitial areas. The specificity of the staining was supported by a variety of staining controls and also by analysis of tissue extracts with ELISA, showing that on the average the inflamed appendices contained more than twice as much mu-PA per mg of protein as the normal appendices and less than one third of the amount of t-PA.