Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting

Expression of mos in ependymal gliomas

The c-mos gene and its protein product mos, components of the mitogen-activated protein kinase transduction pathway, are known to be involved in the control of meiosis and mitosis. Apart from our previous studies on lung carcinomas and astrocytic gliomas, little has been published about its role in human neoplasia. The aim of this study was to investigate the expression of mos in ependymal neoplasms and to correlate it with tumor grade, proliferative fraction, and clinical behavior. We studied mos expression in biopsy specimens from 34 patients with ependymomas. Intracytoplasmic immunopositivity for mos was found in 16 (47%) and was associated significantly with tumor grade: 5 (24%) of 21 grade II ependymomas; 11 (85%) of 13 grade III anaplastic ependymomas (P < .01). Tumors with an MIB-1 labeling index of more than 4% were significantly more likely than those with a lower proliferative fraction to be immunopositive for mos (P = .012). Eypression of mos showed a significant negative association with recurrence-free interval (P = .05) but not with overall survival. Our results suggest that overexpression of mos identifies a biologically aggressive subgroup of ependymal tumors and may be involved in their neoplastic progression

Expression of mos in astrocytic tumors and its potential role in neoplastic progression

The c-mos gene and its protein product mos, components of the mitogen-activated protein kinase transduction pathway, are known to be involved in the control of meiosis and mitosis. Apart from a study on lung carcinomas, there is little information about its role in human neoplasia. The aim of this study was to investigate expression of mos in astrocytic tumors and to correlate it with accumulation of p53. We studied expression of mos in 62 cases of supratentorial astrocytic tumor. Intracytoplasmic immunostaining for mos was found in 28 (45%) cases: 3 of 20 (15%) grade 2 astrocytomas, 9 of 20 (45%) grade 3 anaplastic astrocytomas, and 16 of 22 (73%) glioblastomas. Immunopositivity for mos correlated significantly (P < 0.01) with tumor grade but not with p53 expression. In contrast to the findings in relation to lung tumors, immunopositivity for mos in astrocytic tumors did not predict recurrence-free or overall survival time. Cyto-plasmic immunostaining was observed in scattered large cortical neurons adjacent to tumors, possibly due to stress-induced abortive entry into the cell cycle. The correlation of mos immunopositivity with tumor grade may reflect the expansion of more malignant mos-positive clones. This study provides evidence that mos may be involved in the neoplastic progression of a proportion of astrocytic tumors. Hum PATROL 33:703-707. Copyright 2002, Elsevier Science (USA). All rights reserved

Simultaneous evaluation of maspin and CXCR4 in patients with breast cancer

Aim: To study simultaneously the actions of maspin and CXCR4, which share several similar pathways in cancer, including apoptosis and angiogenesis. Methods: Our material consisted of 151 invasive breast carcinomas arranged in a tissue microarray setting. Maspin and CXCR4 expression was evaluated by immunohistochemistry. Microvessel density was assessed by CD34 immunodetection and apoptosis by the Tdt-mediated dUTP nick end labelling assay. Results: Maspin expression was related to CXCR4 expression, apoptosis, patient age and the Nottingham prognostic index. The expression of both maspin and CXCR4 progressively increased in high-grade tumours. In patients with lymph node negative breast cancer, maspin overexpression was associated with increased risk of death. High CXCR4 expression was associated with prolonged survival of patients with high maspin expression. Conclusions: Our results show that maspin overexpression could prove to be a potentially useful marker, especially for the clinically important group of patients with lymph node negative breast cancer. The expression of CXCR4 is of less significance in our study, but may be informative for specific patient subsets or in a longer time frame