Short-Term Prognostic Index for Breast Cancer: NPI or Lpi.

Axillary lymph node involvement is an important prognostic factor for breast cancer survival but is confounded by the number of nodes examined. We compare the performance of the log odds prognostic index (Lpi), using a ratio of the positive versus negative lymph nodes, with the Nottingham Prognostic Index (NPI) for short-term breast cancer specific disease free survival. A total of 1818 operable breast cancer patients treated in the University Hospital of Leuven between 2000 and 2005 were included. The performance of the NPI and Lpi were compared on two levels: calibration and discrimination. The latter was evaluated using the concordance index (cindex), the number of patients in the extreme groups, and difference in event rates between these. The NPI had a significant higher cindex, but a significant lower percentage of patients in the extreme risk groups. After updating both indices, no significant differences between NPI and Lpi were noted.

Cathepsin B, cathepsin H, cathepsin X and cystatin C in sera of patients with early-stage and inflammatory breast cancer.

Numerous studies have linked cathepsins and their inhibitor cystatin C to tumor invasion and metastasis. We examined whether cathepsin B, cathepsin H, cathepsin X and cystatin C could be detected in sera from women with early stage or inflammatory breast cancer and whether they correlated with clinicopathological characteristics. Preoperative serum was obtained from 176 patients with early-stage breast cancer (tumor size

Clinicopathological features of inflammatory versus noninflammatory locally advanced nonmetastatic breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. It is mainly a clinical diagnosis. The aim of this study was to compare IBC to clinically diagnosed noninflammatory locally advanced nonmetastatic breast cancer, also called cLABC. MATERIAL AND METHODS: One hundred and eight patients were studied: 49 with IBC and 59 with cLABC. The following features were analyzed: age at diagnosis, body mass index (BMI), axillary lymph node status (cN), estrogen receptor status (ER), progesterone receptor status (PR), HER2 status, histological tumor grade and subtype. Short-term disease-free (DFS) and overall survival (OS) were also assessed in both groups. RESULTS: Compared with cLABC, IBC was less often PR positive (41.7 vs. 66.1%, p = 0.01) and showed a trend to be more often HER2 positive (34.7 vs. 19.3%, p = 0.07). The 3-year DFS was 63 and 77%, respectively, for IBC and cLABC (p = 0.01); these figures were 83 and 85% for OS (p = 0.17). No significant differences in age at diagnosis, ER, cN, BMI, histological tumor grade or subtype were demonstrated. CONCLUSION: Compared to cLABC, IBC are more frequently PR negative, have a worse DFS, and have a tendency to be more often HER2 positive. These data reinforce the idea of IBC being a distinct biological entity compared to noninflammatory breast cancer.

Age interacts with the expression of steroid and HER-2 receptors in operable invasive breast cancer.

BACKGROUND: The negative association between the oestrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER-2) in breast cancer travels in both directions. ER+ tumours are less likely HER-2+ and HER-2+ tumours are less likely ER+. METHODS: We studied the age-related immunohistochemical (IHC) expression of ER, progesterone receptor (PR) and HER-2 in 2,227 tumours using age as a continuous variable. Steroid receptors were considered positive for any nuclear staining of invasive cancer cells and for HER-2, either for strong expression by IHC (score 3+) or gene amplification by fluorescence in situ hybridisation (FISH). Based on nonparametric regression, the age-related association between steroid receptors and HER-2 was presented as likelihood curves. RESULTS: The association between ER or PR and HER-2 is age-related. The age-related expression of ER and PR is HER-2 dependent. In HER-2(-) cases, the odds ratio (OR) for being ER+ was 2.594 (95% CI = 1.874-3.591) up to age 50 and age-independent thereafter; for PR-expression the OR was 2.687 (95% CI = 1.780-4.057) up to age 45 and 0.847 (95% CI = 0.761-0.942) thereafter. In HER-2+ cases, the OR was 0.806 (95% CI = 0.656-0.991) to be ER+ and 0.722 (95% CI = 0.589-0.886) to be PR+. The age-related OR for breast cancers to be HER-2+ is steroid receptor dependent. Taking together, ER+PR+HER-2+ breast cancers appear on average 5.4 years earlier than breast cancers of any other ER/PR/HER-2 phenotype (95% CI = 3.3-7.5; P < 0.0001). CONCLUSION: There is a qualitative interaction between age and expression of steroid and HER-2 receptors. Our findings suggest a strong age-related selective growth advantage for breast tumour cells belonging to the ER+PR+HER-2+ subgroup.

Matrix metalloproteinase expression patterns in luminal A type breast carcinomas.

OBJECTIVE: Aberrant expression of individual matrix metalloproteinases has been associated with poor prognosis in various human carcinomas. The current study aimed at defining an RNA expression profile of various MMPs in breast cancer and correlating their expression with clinicopathological parameters. METHODS: The RNA expression patterns of 6 MMPs (MMP2, MMP8, MMP9, MMP10, MMP11, MMP13) were determined in 25 breast carcinomas using quantitative RT-PCR and correlated with clinicopathological parameters, including menopausal status, tumor size and grade, and lymph node involvement. RESULTS: We observed high MMP2 levels more frequently in premenopausal than in postmenopausal women (p=0.02). Analysis of luminal A type invasive ductal carcinomas (19/25), revealed an even stronger association of MMP2 with menopausal status (p=0.005). Within this subgroup, we also found a correlation between MMP11 and menopausal status (p=0.02). No correlation was found between MMP expressions and other clinicopathological parameters. In co-expression analyses MMP2-MMP10 and MMP8-MMP9 showed a weak correlation of their expression. CONCLUSIONS: Although this is a pilot study, our findings indicate that luminal A invasive ductal carcinomas commonly express high MMP2 and MMP11 levels in premenopausal breast cancer patients and suggest a co-regulation of MMP2-MMP10 and MMP8-MMP9.

Body mass index and HER-2 overexpression in breast cancer patients over 50 years of age.

PURPOSE: In breast cancer, in vitro as well as in vivo experiments have shown an inverse relationship between HER-2 and steroid hormone receptors. It is unknown whether circulating estrogens affect HER-2 expression. We hypothesize that the postmenopausal body mass index (BMI) as a surrogate marker for bio-available estrogens, is inversely associated with HER-2 over-expression. PATIENTS AND METHODS: A total of 535 women over age 50 or with known postmenopausal status, with a unilateral, not previously treated, operable breast cancer were evaluated the evening prior to surgery for body weight, height, abdominal and hip circumference over a 3 years period. Waist-to-hip ratio (WHR) and BMI were calculated. HER-2, estrogen receptor and progesterone receptor staining was done by immunohistochemistry. All tumours with DAKO 2+ staining were submitted for HER-2 detection by FISH analysis. HER-2 was defined as positive if DAKO 3+ or FISH positive. We assessed the frequency of HER-2 positivity in each of 6 quantiles for all parameters of body composition and tested for a trend in HER-2 expression across the 6 quantiles. Furthermore, we investigated whether BMI contributed, together with other known predictors for HER-2, in a standard multivariate logistic regression model that predicts HER-2 over-expression. RESULTS: There is a decrease in HER-2 over-expression per increasing quantile of BMI. In a multivariate model-including both steroid receptors-BMI remains an independent predictor for HER-2 over-expression. CONCLUSION: In women over age 50 or with known postmenopausal status with an operable breast cancer, there is an inverse association between BMI and HER-2 over-expression.

Plasma gelatinase levels in patients with primary breast cancer in relation to axillary lymph node status, Her2/neu expression and other clinicopathological variables.

Matrix metalloproteinases (MMPs), in particular the gelatinases MMP2 and MMP9, are important mediators of tumour invasion and metastasis. We examined whether plasma gelatinase levels could predict lymph node metastasis in breast cancer patients. Further, we investigated the relationship of plasma gelatinase levels with Her2/neu expression, recently acknowledged as an important prognostic factor for recurrence, and with various clinicopathological factors. Preoperative plasma samples from 81 breast cancer patients were collected. Total and active gelatinase levels were measured by enzyme immunoassays and activity assays, respectively. Neither total nor active plasma MMP2 levels correlated with nodal status or with any of the classical clinicopathological factors including histological tumour type, tumour size and grade and hormone receptor status. Patients with Her2/neu overexpressing tumours showed an increase of 27% (P=0.007) in plasma MMP2 activity, but not in total MMP2, compared with patients without overexpression. MMP9 levels, total and active, did not correlate with any of the investigated variables. In contrast to MMP9, total MMP2 levels correlated significantly with active MMP2 levels. In summary, total and active plasma gelatinase levels failed to identify high risk for axillary lymph node metastasis. Active plasma MMP2 was significantly increased in patients with Her2/neu overexpressing tumours, suggesting a role for Her2/neu in the signalling pathways of MMP2 activation in carcinogenesis. However, this increase was too small to be of clinical use. Furthermore, no relationship was found between plasma gelatinase levels, total or active, and any of the clinicopathological prognostic factors.

Colonization of rabbits with Staphylococcus aureus in flocks with and without chronic staphylococcosis.

Rabbits of 19 rabbitries were examined for the presence of Staphylococcus aureus in nine different body sites. Seven rabbitries experienced epidemically spreading signs of staphylococcosis while the other 12 rabbitries did not. S. aureus was isolated in all seven flocks that suffered from chronic problems of staphylococcosis and in 11 of the 12 clinically healthy flocks. The mean percentage of infected animals in these two groups was 90 and 43.3%, respectively. S. aureus was isolated from all body sites examined, but the ear and the perineum were often more intensely colonized. The number of animals colonized with S. aureus and the mean number of positive body sites in S. aureus positive rabbits were significantly higher in rabbitries with chronic staphylococcosis. This indicates that colonization capacity of S. aureus plays a role in epidemically spreading disease in rabbits. S. aureus isolates belonged to five different biotypes and 23 different phage types. Several different types simultaneously circulated in contaminated rabbitries and even simultaneously infected individual rabbits. Strains that belonged to the biotype-phage type combination mixed CV-C, 3A/3C/55/71 only occurred in rabbitries chronically dealing with signs of staphylococcosis. This may indicate a relationship between phenotypic strain properties and virulence of S. aureus.

A new pathogenic Staphylococcus aureus type in commercial rabbits.

Heavy losses in commercial rabbitries with mainly cutaneous infections were found to be caused by a special Staphylococcus aureus type. This type differs from the previously known rabbit and hare pathogenic strains causing similar infections, mainly in its unique phage type.

Primary pathogenicity of an European isolate of Chlamydia psittaci from turkey poults.

Chlamydia psittaci was isolated as the sole pathogenic agent from a severe outbreak of respiratory disease in a commercial broiler turkey farm in the Netherlands. The mortality rate in the flocks was 65%. Clinical signs included conjunctivitis, swelling of the sinus infraorbitalis and sneezing. Cloacal excretion of chlamydia was demonstrated in twelve out of fifteen birds examined by a direct immunofluorescence test. In all the fifteen birds antibodies against Chlamydia psittaci were detected in the sera by a competitive ELISA. At necropsy sinusitis, rhinitis, airsacculitis, pneumonia, pericarditis and enlargement of the liver and spleen were found. Chlamydiae were demonstrated in the sinus material of all and in conjunctival smears of eight of the fifteen examined birds. Chlamydiae were isolated from all the examined birds after one to three passages on Buffalo Green Monkey (BGM) cell cultures using samples taken from lung, liver and spleen. No other pathogens were isolated. The chlamydia isolate was typed using a panel of serovar-specific monoclonal antibodies in a micro-immunofluorescence test. The isolate belonged to the avian Chlamydia psittaci serovar D. Experimental inoculation with this isolate of 7-day-old specific pathogen free (SPF) turkeys resulted in severe clinical signs, with mortality and extensive pathological lesions, similar to those seen in turkeys from the examined broiler turkey farm. From the data it was concluded that this Chlamydia psittaci isolate can cause severe disease in turkeys.