Decreased xanthine oxidoreductase is a predictor of poor prognosis in early-stage gastric cancer.

BACKGROUND: Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA and high-energy phosphates. About half of the patients with breast cancer have a decrease in XOR expression. Patients with breast cancer with unfavourable prognosis are independently identified by the loss of XOR. AIM: To assess the clinical relevance of XOR expression in gastric cancer. METHODS: XOR levels were studied by immunohistochemistry in tissue microarray specimens of 337 patients with gastric cancer and the relation between XOR expression and a series of clinicopathological variables, as well as disease-specific survival, was assessed. RESULTS: XOR was moderately decreased in 41% and was undetectable in another 14% of the tumours compared with the corresponding normal tissue. Decreased XOR was associated with advanced stage, deep tumour penetration, diffusely spread tumour location, positive lymph node status, large tumour size, non-curative disease, cellular aneuploidy, high S-phase fraction and high cyclooxygenase-2 expression, but not with p53 expression or Borrmann classification. Down regulation of XOR was associated with unfavourable outcome, and the cumulative 5-year gastric cancer-specific survival in patients with strong XOR expression was 47%, compared with 22% in those with moderate to negative expression (p<0.001). This was also true in patients with stage I-II (p = 0.01) and lymph node-negative (p = 0.02) disease, as well as in patients with smaller (< or =5 cm) tumours (p = 0.02). CONCLUSION: XOR expression in gastric cancer may be a new marker for a more aggressive gastric cancer biology, similar to that previously reported for breast cancer.

MMP-2 but not MMP-9 associated with COX-2 and survival in gastric cancer.

BACKGROUND AND AIM: Matrix metalloproteinases (MMPs) MMP-2 and MMP-9 can degrade type IV collagen of extracellular matrix and basal membranes. As cyclo-oxygenase-2 (COX-2) has been shown to activate MMPs, creating one of the COX-2-promoted pathways of tumour growth and metastasis, the prognostic role of MMP-2 and MMP-9 in gastric cancer was assessed and their association with COX-2 expression was evaluated. MATERIALS AND METHODS: Samples were collected from 342 consecutive patients operated on for gastric cancer, of which 315 were acceptable for MMP-2, MMP-9 and COX-2 immunohistochemistry. Specimens were stained with specific antibodies, evaluated and categorised by two interpreters, and then correlated with clinical data and survival. RESULTS: Epithelial MMP-2 immunoreactivity was associated with male sex, high stage, advanced penetration depth, non-curative surgery, high COX-2 expression and poor survival. Stromal MMP-2 expression correlated with high stage, intestinal type and non-curative surgery whereas MMP-9 correlated only with intestinal type. Stage, intent of surgery and COX-2 were independent prognostic factors. CONCLUSIONS: Epithelial MMP-2 expression in gastric cancer is associated with aggressive forms, COX-2 and poor survival, although MMP-2 was not an independent prognostic factor. In gastric cancer tumour growth is apparently induced by COX-2, and invasion is mediated by MMP-2.

Epithelial syndecan-1 expression is associated with stage and grade in colorectal 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 tissue expression of tumour-associated trypsin inhibitor (TATI) associates with a more favourable prognosis in gastric cancer.

AIMS: The tumour-associated trypsin inhibitor (TATI) is a 6-kDa protease inhibitor with potential inhibitory effects on tissue degradation. In serum, increased levels have been associated with adverse prognosis in different forms of cancer. We assessed the tumour tissue expression and prognostic value of TATI in a surgically treated, single-institution series of patients with gastric cancer. METHODS AND RESULTS: Using a monoclonal anti-TATI antibody, immunohistochemistry was performed on formalin-fixed paraffin-embedded tumour specimens from 336 patients. TATI expression was observed in 265 (79%) of the tumours. There was a significant association between high TATI expression and low stage (P = 0.007), superficial tumours (P = 0.005), and absence of nodal (P = 0.015) and of distant metastases (P = 0.022). In univariate analysis, patients with high TATI expression had a significantly more favourable 5-year cumulative survival compared with patients with negative to moderate immunostaining (43% and 28%, respectively, P = 0.006). On multivariate survival analysis stratified for estimated cure of surgery, stage (P < 0.0001) and age (P = 0.022) at the time of surgery were independent prognostic factors. CONCLUSIONS: High TATI expression in tumour tissue was detected more frequently in patients with early-stage gastric cancer and seems to correlate with a favourable outcome.

Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer.

The prognostic value of the immunohistochemical expression of epithelial and stromal syndecan-1 was evaluated in 296 patients with gastric carcinoma. Formalin-fixed, paraffin-embedded specimens of gastric adenocarcinomas were stained with mouse monoclonal antibody B-B4 against human syndecan-1. Loss of immunoreactivity (syndecan-1 immunoreactivity correlated with a higher stage of disease (stages II-IV), tumour location in the upper third of the stomach, nodal metastases (N1 or N2), positive stromal syndecan-1 staining, deep tumour penetration (to subserosa or deeper = T2-T4), larger tumour size (> or = 5 cm) and intestinal type of cancer. No correlation between epithelial syndecan-1 immunoreactivity and age, gender, distant metastases, grade of differentiation or Borrmann classification was observed. Positive stromal syndecan-1 immunoreactivity correlated with decreased epithelial syndecan-1 expression, intestinal type of cancer and Borrmann type I. Patients with low epithelial syndecan-1 expression in cancer cells had worse overall survival than patients with strong epithelial syndecan-1 staining (p = 0.0012). Stromal syndecan-1-positive patients had a worse outcome than patients with syndecan-1-negative stroma (p = 0.0193). In Cox multivariate analysis, stromal syndecan-1 immunoreactivity was a prognostic factor independent of TNM stage, surgery for cure and tumour size. Thus, the immunohistochemical expression of syndecan-1 might be a predictor of outcome in patients with gastric adenocarcinoma.

A prognostic value of syndecan-1 in gastric cancer.

BACKGROUND: Syndecan-1, a cell surface heparan sulphate proteoglycan, has a role in cell adhesion, maturation and proliferation. Syndecan-1 has been reported to be a promising prognostic marker in various cancer forms. MATERIALS AND METHODS: We analysed tumour specimens from 296 gastric cancer patients. Syndecan-1 expression was studied by immunohistochemistry. RESULTS: Syndecan-1 immunoreactivity was observed in 234 (79%) patients. The expression of syndecan-1 did not correlate significantly with the presence of lymph node metastases, distant metastases, peritoneal spreading, penetration depth, tumour size, tumour location, Borrmann's classification, Laurén's classification, age or gender. Syndecan-1 immunoreactivity correlated significantly with survival in the whole patient series (p = 0.0499) and also in the subgroup of patients with stage I cancer (p = 0.0417), but not in patients with stage II, III or IV disease. In multivariate survival analysis, stage of disease and tumour size emerged as the only independent prognostic factors. CONCLUSIONS: In conclusion, immunohistochemical expression of syndecan-1 is a potential prognostic factor in gastric cancer, especially in patients with stage I disease.

Distal pulse palpation: is it reliable?

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.