Angiogenic factors produced by tumor cells are essential for tumor growth and metastasis. In our study, the expression of Angiopoietin-1 (ANG1) and Angiopoietin-2 (ANG2) mRNA in archival human breast cancer tumor samples and in 6 breast cancer cell lines was investigated. Total RNA from biopsies of 38 breast cancer patients was extracted and ANG1 and ANG2 mRNA expression was measured by means of quantitative real-time RT-PCR (Taqmanா). Matching data with available clinicopathologic and biochemical data revealed a significant association between ANG2 expression and axillary lymph node invasion. Univariate and multivariate survival analysis, by means of Kaplan-Meier method and Cox's proportional hazards model, showed significant and independent association between ANG2 mRNA level and both disease-free (p < 0.0001) and overall survival (p < 0.0003). An important fact is that, notwithstanding the small number of cases examined, this association was confirmed also in the group of lymph node-negative patients (DFS, p < 0.003; OS, p < 0.020). Immunohistochemical analysis demonstrated that Ang2 is expressed by both tumor cells and endothelial elements. Expression in tumor cells was confirmed by studying a panel of human breast carcinoma cell lines in culture by RT-PCR. In ZR75.1 and T47D cells, expression of ANG2 mRNA was increased up to 10-fold by treatment with estrogen within 24 hr. Although preliminary, these data suggest a possible role of ANG2 as a prognostic factor for primary breast cancer.

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Gene expression profiles were studied by microarray analysis in 2 sets of archival breast cancer tissues from patients with distinct clinical outcome. Seventy-seven differentially expressed genes were identified when comparing 30 cases with relapse and 30 cases without relapse within 72 months from surgery. These genes had a specific ontological distribution and some of them have been linked to breast cancer in previous studies: AIB1, the two keratin genes KRT5 and KRT15, RAF1, WIF1 and MSH6. Seven out of 77 differentially expressed genes were selected and analyzed by qRT-PCR in 127 cases of breast cancer. The expression levels of 6 upregulated genes (CKMT1B, DDX21, PRKDC, PTPN1, SLPI, YWHAE) showed a significant association to both disease-free and overall survival. Multivariate analysis using the significant factors (i.e., estrogen receptor and lymph node status) as covariates confirmed the association with survival. There was no correlation between the expression level of these genes and other clinical parameters. In contrast, SERPINA3, the only downregulated gene examined, was not associated with survival, but correlated with steroid receptor status. An indirect validation of our genes was provided by calculating their association with survival in 3 publicly available microarray datasets. CKMT1B expression was an independent prognostic marker in all 3 datasets, whereas other genes confirmed their association with disease-free survival in at least 1 dataset. This work provides a novel set of genes that could be used as independent prognostic markers and potential drug targets for breast cancer. ' 2008 Wiley-Liss, Inc.Key words: breast cancer; gene expression; microarray analysis; prognosticThe heterogeneous nature of breast cancer reflects the complexity of the molecular alterations that underlie the development and progression of this disease and poses serious problems to clinical management, also due to the lack of reliable pathological or molecular markers.There are a number of major open questions, such as the evaluation of risk of distant metastasis in cases characterized by the presence of favorable indicators (negative axillary lymph nodes and/or positive estrogen receptors), the prediction of response to chemotherapy and/or antiestrogenic therapy and the prediction of metastases sites for high-risk cancers. Moreover, the principal molecular alterations leading to aggressive clinical behavior, representing potential therapeutic targets, still need to be identified in addition to the well-known factor ERBB2 and the estrogen receptor pathways.Molecular profiling using DNA microarrays have provided sound advancements in this field. The expression profile of gene clusters were useful in classifying breast tumors in biological subgroups with clinical relevance, 1 or in low-versus high-risk classes for relapse, 2-5 or to predict responsiveness to either hormonal-or chemo-therapy. 6,7 In a well-known study, van't Veer et al. addressed the risk of relapse in node-negative patients, 2 one of the most clinicall...

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The aim of this retrospective investigation was to assess the pattern of failures of 412 patients with recurrent ovarian cancer followed up with different surveillance protocols.Time to recurrence was less than 6 months in 98 women (23.8%), 6 to 12 months in 102 women (24.7%), and more than 12 months in 212 women (51.5%). Symptoms at relapse were referred by 81 women (19.7%). Among the 331 asymptomatic patients, the surveillance procedure that raised the suspect of recurrent disease was clinical examination in 49 (14.8%), imaging technique in 90 (27.2%), serum CA 125 in 77 (23.3%), and both serum CA 125 and imaging technique in 115 (34.7%). At univariate analysis, survival from initial diagnosis was related to stage (P = 0.004), residual disease after initial surgery (P < 0.0001), time to recurrence (P < 0.0001), site of relapse (P = 0.04), and treatment at recurrence (P < 0.0001), and survival after recurrence was related to stage (P = 0.01), residual disease (P < 0.0001), time to recurrence (P < 0.0001), and treatment at recurrence (P < 0.0001). Conversely, symptoms at recurrence had no prognostic relevance. Cox proportional hazards model showed that residual disease and time to recurrence were the only independent prognostic variables for both survival from initial diagnosis (P < 0.0001) and survival after recurrence (P < 0.0001). In conclusion, there was no survival difference between asymptomatic and symptomatic patients at the time of relapse, and therefore, the diagnostic anticipation allowed by a scheduled follow-up protocol did not seem to improve the clinical outcome of patients who ultimately developed recurrent disease.

Elderly EOC patients can receive an adequate treatment, but patients who are older than 75 years can be undertreated, if not adequately selected. The pretreatment assessment of frailty through mFI could be suggested in the surgical and medical management.

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A B S T R A C T PurposeTo assess whether the interval from primary surgery to the start of taxane-plus platinum-based chemotherapy has any impact on the clinical outcome of advanced ovarian cancer patients. Patients and MethodsThe study was conducted on 313 patients who underwent surgery followed by taxane-plus platinum-based chemotherapy. The median follow-up of survivors was 30.7 months (range, 6 to 109 months). ResultsThe 25%, 50%, and 75% quantiles of intervals from surgery to the start of chemotherapy were 11, 21, and 31 days, respectively. After the sixth cycle, 102 patients achieved a pathologic complete response at second-look surgery and 98 obtained a clinical complete response but were not submitted to second-look surgery. Taking into consideration the best assessed response, a complete (either clinical or pathologic) response was found in 200 patients. Residual disease (Յ 1 v Ͼ 1 cm; P Ͻ .0001) and ascites (absent v present; P ϭ .003) were independent predictive factors for achieving a complete response, whereas residual disease (P ϭ .001) and stage (IIc to III v IV; P ϭ .04) were independent prognostic variables for survival. Conversely, statistical analyses failed to detect significant differences in complete response rates and survival among patients with an interval from surgery to chemotherapy shorter than 11 days, 12 to 21 days, 22 to 31 days, and longer than 31 days. ConclusionThe interval from surgery to the start of taxane-plus platinum-based chemotherapy seems to have neither a predictive value for response to treatment nor a prognostic relevance for survival of advanced ovarian cancer patients.