CIP2A immunopositivity is a predictor of survival for some subgroups of gastric cancer patients. CIP2A and MYC appear to be regulated in a positive feedback loop, wherein they promote each other's expression and gastric cancer cell proliferation.

Purpose: Cyclooxygenase-2 (COX-2) promotes carcinogenesis and its expression associates with clinicopathologic characteristics in gastric cancer. HuR is an mRNA binding protein that controls the stability of certain transcripts including COX-2.We evaluated the prognostic significance of COX-2 and HuR expressions in gastric cancer and whether there exists a link between HuR and COX-2 expressions. Experimental Design: The study included 342 consecutive patients with histologically confirmed gastric adenocarcinoma, of whom 321patients had tissue specimens available for COX-2 and 316 for HuR immunohistochemistry. Specimens were stained by COX-2^and HuR-specific monoclonal antibodies and scored by two independent observers. Correlation to clinical data and survival was assessed. TMK-1 gastric adenocarcinoma cells were treated with small interfering RNA against HuR and expressions of HuR and COX-2 were detected by immunofluorescence andWestern blot analysis. Results: Patients with low COX-2 expression had a cumulative 5-year survival of 53% and those with high COX-2 expression had 16% (P < 0.0001). In multivariate analysis, COX-2 was an independent prognostic factor (P = 0.003). Cytoplasmic HuR expression was associated with high COX-2 expression (P < 0.0001) and with reduced survival (P = 0.004) whereas nuclear positivity for HuR was not. When TMK-1 cells were treated with HuR small interfering RNA, expressions of HuR and COX-2 were reduced. Conclusions: High COX-2 is an independent prognostic factor in gastric cancer. Cytoplasmic expression of HuR associates with high COX-2 expression and with reduced survival, and tissue culture experiments show that HuR can regulate expression of COX-2 in gastric cancer cells.

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The aim of this study was to evaluate the reliability of distal pulse palpation. The dorsalis pedis and the tibialis posterior arteries of 25 patients with suspected lower limb arterial disease were independently palpated by three vascular surgeons and three medical students in the outpatient clinic and by two vascular nurses and one physician in the vascular laboratory. The palpation findings were compared to the ankle/brachial index (ABI). Palpable and unpalpable pulses were best separated with ABI 0.76 as the cutoff point. The degree of misdiagnosis was unacceptably high, with an underdiagnosis of more than 30%. The agreement was highest (kappa 0. 68, good) among the vascular laboratory personnel in the peaceful vascular laboratory and lowest (kappa 0.38, fair) among the vascular surgeons in the busy outpatient clinic. The poor agreement and the high proportion of misdiagnosis obtained in the outpatient clinic argue against the use of pulse palpation as a single diagnostic method. Palpable pulses with low ABIs clearly state the need for more objective measurements whenever ischemia is suspected. Yet, by carefully palpating both pedal arteries under good, nonhurried conditions the reproducibility and accuracy of pulse palpation can be tolerable.

To enable cancer to invade and to metastasize, the surrounding stroma must be degraded. Matrix metalloproteinase-7 (MMP-7) is capable of degrading many extracellular matrix proteins and cellular adhesions, is overexpressed in many malignancies, and plays a role in tumour progression. The purpose of this study was to evaluate the association between MMP-7 tissue expression and patients' prognosis in gastric cancer. From 264 patients who underwent surgery for gastric cancer, surgical specimens were collected on tissue array blocks and stained by immunohistochemistry for MMP-7. In 27 (10.2%) of the specimens, immunopositivity was found as high, in 50 (18.9%) as moderate and in 51 (19.3%) as weak. In 136 cases (51.5%), the immunopositivity was negative. A statistically significant correlation appeared between high MMP-7 expression and poor survival. In conclusion, our results suggest that MMP-7 expression may prove helpful in evaluating gastric cancer prognosis.

Objectives: p27 is a cyclin-dependent kinase inhibitor and a putative tumor suppressor preventing progression of the cell cycle from G1 phase. Recent studies have suggested loss of p27 to correlate with poor prognosis in patients with a variety of solid tumors. Results in gastric cancer are contradictory. We therefore decided to study the potential of p27 as a prognostic marker in a consecutively surgically treated, single-institution series of patients. Methods: Using a monoclonal antibody against p27, immunohistochemistry was performed in paraffin-embedded tumor specimens from 316 patients. Results: Loss of p27 immunoreactivity (≤5% of the cancer cell nuclei positive) was observed in 241 (76%) out of 316 stained tumors. We observed no significant correlation between the expression of p27 and stage of disease, tumor size, depth of tumor invasion, lymph node metastases, distant metastases, Laurén classification, Borrmann type, grade of differentiation, age or gender. There was no significant difference in gastric cancer specific overall survival between patients with low and high p27 expression. Conclusion: Our results add further doubt to the usefulness of p27 as a prognostic marker in gastric cancer.

Objectives: Loss of epithelial heparan sulfate proteoglycan syndecan-1 has been associated with a more aggressive behavior in various cancer forms, but the prognostic significance of syndecan-1 expression in colorectal cancer is unclear. The aim of this study was to evaluate the prognostic value of immunohistochemical syndecan-1 expression in a series of 237 patients with colorectal cancer. Methods: Paraffin-embedded formalin-fixed specimens were stained with a syndecan-1-specific monoclonal antibody, and both the epithelial and stromal expression were analyzed. Results: Epithelial expression of syndecan-1 was seen in 222 tumors (94%), and it was associated with low stage of disease (p = 0.002) and low histological differentiation grade (p = 0.048). The cumulative 5-year survival of patients with weak and strong syndecan-1 expression was 49 and 54 %, respectively (p = 0.234). Syndecan-1 stromal immunoreactivity was observed in 138 tumors (58%), but lacked prognostic significance. Staining pattern and distribution can be viewed from digitized representative microscope slides (virtual slides) at http://www.webmicroscope.net/supplements/syndecan. Conclusions: The results are in line with previous reports in that low epithelial syndecan-1 expression was associated with a higher histological grade and a more advanced clinical stage of the patients. This study shows that syndecan-1 is expressed also in stromal tissue of colorectal cancer, but it does not support the proposed role of stromal syndecan-1 expression as a marker of poor clinical outcome.

High level of cyclin A promotes carcinogenesis, and overexpression of cyclin A has been associated with poor prognosis of cancer patients. We validated the prognostic role of cyclin A in gastric cancer and evaluated its correlation with expression of an mRNA stability factor HuR. From 342 consecutive histologically confirmed gastric cancer patients were obtained 325 representative tissue specimens for cyclin A and 316 for HuR immunohistochemistry. Specimens were stained by cyclin A and HuR specific monoclonal antibodies. Nuclear immunostaining detected in 5% of the tumor cells was considered the cut-off for cyclin A positivity. Positive HuR immunoreactivity was scored as nuclear or cytoplasmic. Associations between scores, clinicopathological factors and survival were calculated by the v 2 -test, Fisher's exact test, Kaplan-Meier test and Cox model. Cyclin A detected in the nuclei of cancer cells was positive in 55% (179 of 325) of the specimens; 40% (127 of 316) of the specimens had cytoplasmic and 88% (279 of 316) nuclear immunoreactivity of HuR. Cyclin A expression was an independent prognostic factor for poor survival. Cyclin A immunoreactivity was associated with old age, high stage, proximal location of the tumor, intestinal type, noncurative resection, advanced penetration depth and with nodal metastases but not distant metastases. Furthermore, cyclin A expression was associated with cytoplasmic HuR expression, whereas no association with nuclear HuR was evident. Cyclin A is an independent prognostic factor in gastric cancer, and one mechanism for its overexpression may depend on cytoplasmic localization of HuR. ' 2006 Wiley-Liss, Inc.Key words: cyclin A; HuR; gastric cancer; prognosis; survival Cyclin A belongs to the cyclin protein superfamily, and it can activate two different cyclin-dependent kinases, CDK1 and CDK2. The level of cyclin A accumulates progressively throughout the interphase and disappears rapidly at the end of mitosis. Currently, phosphorylated cyclin A-CDK complex is suggested to play an important role in the initiation of DNA replication in the S phase. The precise function of cyclin A in mitosis is unclear, but it may prevent other cyclins from degradation. Overexpression of cyclin A and dysregulation of CDK-cyclin complexes promote tumor cell growth, which can be facilitated by phosphorylation of oncoproteins and tumor suppressors. 1,2 In gastric cancer, cell-cycle regulators have been connected with poor prognosis. For example, overexpression of cyclin E, which also binds to CDK2 and controls the G1-S transition, has been associated with aggressive disease. 3,4 Furthermore, strongly positive cyclin E in the tumors of patients having surgery with intent to cure is a marker of poor prognosis, and concurrent expression of cyclin E and p53 is an independent prognostic factor. 5 However, there are also reports indicating that cyclin E expression does not correlate with clinicopathological parameters, 6 or is associated with good prognosis. 7 Overexpression of cyclin A correlates with po...