Subset Of Node-negative Patients Research Articles

A Ploidia de ADN é um Biomarcador Prognóstico Independente no Carcinoma Ductal Invasivo da Mama

To evaluate 'classic' prognostic parameters, as well as DNA ploidy and S-phase fraction, in relation to disease-free and overall survival in breast invasive ductal carcinoma with long-term follow-up. The study involved 400 patients with breast invasive ductal carcinoma and median follow-up of 134 months (50-240). Histological grading, tumour size, axillary nodal involvement, pathological staging and hormone-receptor status were assessed as established prognostic markers. Ploidy and S-phase fraction were determined prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables. There were 106 deaths (26.5%) and 141 disease recurrences (35.2%) during follow-up. Two hundred thirty-five (58.7%) tumours were aneuploid. High S-phase fraction and aneuploidy were associated with tumours with higher grade of differentiation, greater size and negative hormonal receptors. In univariate analysis, all the clinicopathological and cytometric features (including patients < 40 years and a subgroup presenting hipertetraploid/multiploid tumours), but S-phase fraction and estrogen receptors for disease free survival, significantly correlated with clinical outcome. In multivariate analysis, advanced disease stage, DNA aneuploidy and lack of progesterone receptors retained statistically significant association with shorter survival. In the subgroup of patients with intermediate differentiation tumours (G2), aneuploidy associated with worse prognosis. In the subset of node-negative patients, only estrogen receptors showed significant correlation with disease evolution. In node-positive patients, greater size tumours and aneuploidy (in relation to overall survival) were indicators of worse prognosis. Along with disease staging and hormone-receptor expression, DNA ploidy is an independent prognostic biomarker of long-term survival in breast invasive ductal carcinoma.

Prognostic significance of angiogenesis evaluated by CD105 expression compared to CD31 in 905 breast carcinomas: Correlation with long-term patient outcome

Our purpose was to determine the respective prognostic significance of CD105 and CD31 immunoexpression in node negative patients with breast carcinoma, since angiogenesis induces blood borne metastases and death in carcinomas. CD105 (endoglin) has been reported as expressed by activated endothelial cells and consequently should better reflect neoangiogenesis in malignant tumors. Comparison of CD31 and CD105 immunocytochemical expression was undertaken in a series of 905 breast carcinomas. Results were compared to patients' long-term (median = 11.3 years) outcome. Univariate (Kaplan-Meier) analysis showed that the number of CD105+ microvessels (cut-off 15 vessels) correlated significantly with poor overall survival (p=0.001). This correlation was less significant in node negative patients (p=0.035). The number of CD31+ microvessels (cut-off 25 vessels) similarly correlated with poor survival (p=0.032) but not in the subgroup of node negative patients. Marked CD105 expression also correlated with a high risk for metastasis in all patients (p=0.0002) and in the subset of node negative patients (p=0.001). Similarly metastasis risk in node negative patients correlated with marked CD31 immunocytochemical expression (p=0.02). Multivariate analysis (Cox model) identified CD105, but not CD31 immunoexpression, as an independent prognostic indicator. Our results suggest that: i) in breast carcinomas, immunoselection of microvessels containing activated CD105 labelled endothelial cells is endowed with a stronger prognostic significance, as compared to CD31 vessels labelling; ii) the CD105 immunoexpression may be considered as a potential tool for selecting node negative patients with a poorer outcome and higher metastasis risk; iii) in these patients specific antiangiogenic therapy targeted by anti-CD105 conjugates can be further developed.

Biological indicators of survival in patients treated by surgery for squamous cell carcinoma of the oral cavity and oropharynx

Squamous cell carcinomas of the head and neck are a heterogeneous group of tumours with regard to anatomical site, natural history and response to various treatments. Assessment of the role of biomarkers as indicators of prognosis or response to treatment is thus complex. In the last decade, different biomarkers have been investigated in the search for objective and reproducible indicators of prognosis. In 69 squamous cell carcinomas of the oral cavity or oropharynx from patients treated with radical surgery alone, we determined cell kinetics, evaluated as in vitro 3H-thymidine labelling index (TLI), p53, bcl-2 and glutathione S-transferase pi (GST pi) expression, by using immunohistochemical methods. The biological variables were unrelated to one another or to established clinical and pathological prognostic factors. Univariate analysis showed that a low proliferative activity was associated to a significantly higher risk of death than that observed in patients with a high TLI, whereas p53, bcl-2 and GST pi expression did not provide prognostic information. Multivariate analysis showed that cell proliferation, gender and nodal status retained their clinical relevance. In the subset of node-negative patients, TLI and p53 expression were indicators of survival. Moreover, the combined analysis of TLI and p53 expression identified a subgroup of node-negative patients with slowly proliferating and highly p53-expressing tumours who died within 1 year of radical surgery. These results indicate that in patients with operable oral cavity and oropharyngeal cancer, biomarkers can provide important information on clinical outcome.

Preoperative carcinoembryonic antigen predicts outcomes in node-negative colon cancer patients: a multivariate analysis of 572 patients

Background: Although prospective trials have demonstrated that postoperative chemotherapy for nodepositive colon cancer patients provides survival benefit, no improvement in survival has been documented for node-negative colon cancer patients. There are, however, a subset of node-negative patients that go on to die of their disease. We hypothesize that this subset of node-negative patients may benefit from postoperative chemotherapy. We analyzed a large cohort of nodenegative colon cancer patients from a single institution to determine prognostic factors that predict which patients with node-negative colon cancer might experience recurrence and can benefit from postoperative chemotherapy. Study Design: A review of the prospective database for colorectal cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1985 and 1993 identified 572 patients who underwent curative resection for nodenegative colon cancer (T 1,2,3,4N 0M 0). Demographic, serum, and pathologic factors were analyzed for prognostic significance. Survival was calculated by the method of Kaplan-Meier and compared by log rank test. Multivariate analysis was calculated by the Cox proportional hazard model. Results: Median follow-up was 35 months. Factors predictive of survival by univariate analysis include tumor stage, overall stage, and preoperative serum carcinoembryonic antigen (CEA) elevation. By multivariate analysis, overall stage and preoperative serum CEA level predicted survival. Conclusions: Routine histologic and demographic factors do not predict outcome in node-negative colon cancer patients. Preoperative CEA and overall stage predict survival by multivariate analysis. Preoperative CEA elevation in node-negative patients identifies a group of patients that has a poor prognosis and defines a subset of patients who may benefit from postoperative chemotherapy.

Preoperative carcinoembryonic antigen predicts outcomes in node-negative colon cancer patients: a multivariate analysis of 572 patients.

Although prospective trials have demonstrated that postoperative chemotherapy for node-positive colon cancer patients provides survival benefit, no improvement in survival has been documented for node-negative colon cancer patients. There are, however, a subset of node-negative patients that go on to die of their disease. We hypothesize that this subset of node-negative patients may benefit from postoperative chemotherapy. We analyzed a large cohort of node-negative colon cancer patients from a single institution to determine prognostic factors that predict which patients with node-negative colon cancer might experience recurrence and can benefit from postoperative chemotherapy. A review of the prospective database for colorectal cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1985 and 1993 identified 572 patients who underwent curative resection for node-negative colon cancer (T(1,2,3,4)N0M0). Demographic, serum, and pathologic factors were analyzed for prognostic significance. Survival was calculated by the method of Kaplan-Meier and compared by log rank test. Multivariate analysis was calculated by the Cox proportional hazard model. Median follow-up was 35 months. Factors predictive of survival by univariate analysis include tumor stage, overall stage, and preoperative serum carcinoembryonic antigen (CEA) elevation. By multivariate analysis, overall stage and preoperative serum CEA level predicted survival. Routine histologic and demographic factors do not predict outcome in node-negative colon cancer patients. Preoperative CEA and overall stage predict survival by multivariate analysis. Preoperative CEA elevation in node-negative patients identifies a group of patients that has a poor prognosis and defines a subset of patients who may benefit from postoperative chemotherapy.

Comparison of estrogen and progesterone receptor status to lymphocyte immunity against tumor antigens in breast cancer patients

Estrogen (ER) and progesterone receptor (PgR) content of tumors were determined by both the dextran-coated charcoal (DCC) cytosol and immunocytochemical assays (ICA), and these hormone receptor results were compared to lymphocyte immunity against tumor antigen(s) for 52 breast carcinoma patients. Hormone receptor analysis by both methods demonstrated that 60% of the patients' tumors had ERs, while 44% were positive for PgRs. The ICA procedure was more sensitive than the cytosol technique for determining PgR content of the tumors. This increased sensitivity was not observed for ER by ICA. Patient age, tumor size, and nodal status were not related to the ER and PgR receptor status. A total of 21/52 (40%) of the patients had positive lymphocyte immunity against tumor antigen. This immunity was independent of patient age, tumor size, and nodal status. There was no significant relationship between lymphocytic immunity against tumor antigen and ER or PgR content of tumors, suggesting that patient lymphocyte immunity against tumor is independent of hormone receptor status. This is further evidence that lymphocyte immunity against tumor antigen status is an independent prognostic indicator that may be useful in the selection of a subset of node negative patients for adjuvant chemotherapy.

Prognostic significance of her‐2/neu expression in breast cancer and its relationship to other prognostic factors

Archival surgical specimens from 1,210 female breast cancer patients treated between 1968 and 1971 and with a 19-year follow-up were reanalyzed with special reference to several parameters, such as size of the primary tumor, axillary nodal involvement, histologic grade, degree of inflammatory infiltrate (LPI) of the tumor and expression of the neu oncoprotein (p185) as detected by immunohistochemistry. In a multifactorial analysis the 4 former factors were found to be independent prognostic parameters. Over-expression of p185 was found to be related to tumor size and grade and to LPI but not to pathologic nodal status. Over-expression of p185 showed a negative impact upon survival in node-positive but not in node-negative patients. However, in the subset of node-negative patients without LPI, p185 over-expression showed the same correlation with a poor prognosis as in node-positive patients. In contrast, in node-negative and LPI-positive patients, p185 over-expression correlated with a good prognosis. Also, the prognosis of patients with positive nodes, presence of LPI and no p185 over-expression was similar to that of patients with negative nodes, absence of LPI and p185 over-expression.