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Development of multiple tumors of different histopathologic types may suggest a profound generalized genetic defect, such as malfunction of DNA mismatch repair (MMR) mechanism. Defects in this mechanism are best reflected in microsatellite instability (MSI). We aimed to determine the role of MSI in a group of patients with dual malignancies and compared the data with that of patients with a single malignancy. Fifty patients were enrolled in the study, of whom 16 patients developed both solid and hematologic nonfamilial malignancies, 18 patients developed a single matched hematologic malignancy, and 16 a single matched solid malignancy. Five microsatellite markers were replicated by polymerase chain reaction (PCR) after DNA extraction from paraffin-embedded tissue blocks and analyzed by the GeneScan Analysis Software. The MSI-high phenotype was defined as instability in at least 40% of the examined loci. A higher prevalence of MSI-high phenotype was found in patients with dual malignancies (31.3%) compared with patients with single hematologic (5.6%) or solid malignancy (6.3%) (P = 0.0498 and 0.07, respectively). In conclusion, defects in DNA MMR mechanism may have an important role in the development of multiple sporadic nonfamilial malignancies.

Background and Objectives: Phyllodes tumor (PT) is a biphasic tumor with unpredictable behavior. Our study aimed to evaluate clinicopathologic factors and biomarkers that may be helpful in predicting the outcome of these tumors., Methods: We evaluated immunoreactivity of p53, c-erbB-2, and Ki-67 in 23 PT treated over a 10-year period. The proliferative activity in PT and expression of p53 and c-erbB-2 were correlated with clinicopathologic features of the tumors and patients' outcome., Results: Positive stromal p53 immunoreactivity was found in PT with atypia, infiltrative borders, high cellularity, as well as in PT that displayed higher then average proliferation index, although none of these parameters reached statistical significance. There was a good correlation between proliferative stromal cell activity expressed Ki-67-labeling index and the malignant features of the tumors. Primary tumors that recurred displayed high proliferative activity. Three of four recurrent tumors showed a progression toward higher malignant phenotype with concomitant increase in proliferative stromal cell activity. c-erbB-2-positive tumors had no particular histologic features or association with either p53 positivity or higher proliferative indices., Conclusions: p53 expression tends to be more frequent in PT with higher malignant potential but did not predict recurrence. Incompletely excised tumors that recurred displayed high proliferative activity in their primary tumors. Progression toward more malignant phenotype in the recurrent PT was accompanied with increase in stromal cell proliferative activity, suggesting the presence of biological continuity between benign, borderline, and malignant PT., (Copyright 2002 Wiley-Liss, Inc.)

Background and Objectives: p53, c-erbB-2, and tumor microvascular density have been shown to be potential prognostic tools in female breast cancer. Our objective was to assess the significance of these biomarkers as prognostic factors in infiltrating male breast cancer., Methods: A retrospective study of expression of p53, c-erbB-2, and tumor microvascular density was done on a group of 26 male breast cancer patients. Biotin-streptavidin immunohistochemical study with specific anti-p53, anti-c-erbB-2, and anti-CD34 antibodies was carried out on paraffin sections of breast carcinoma. The data of expression of the biomarkers were merged with clinicopathological data such as tumor grade, T class, TNM stage, estrogen receptor status, tumor recurrence, and patient survival., Results: p53 and c-erbB-2 were expressed in 46% and 39% of carcinomas, respectively. No correlation was found between positive immunoreactivity of p53, and tumor grade, size, T class, TNM stage, and survival. Nor was any relation found between tumor size, T class, TNM stage, survival, and c-erbB-2 overexpression. c-erbB-2 overexpression was significantly higher in high grade carcinomas. Estrogen receptor (ER) were positive in 21 out of 26 of tumors (81%). No trends were observed between estrogen receptor status and clinicopathological parameters or survival (data not shown). There was a positive correlation between mean microvascular density (MVD), advanced T class, and survival: higher MVD counts were found in patients with advanced tumors and in those who had tumor relapses or died of metastatic disease., Conclusions: This study suggests that tumor microvascular density may serve as a potential prognostic tool in male breast carcinoma., (Copyright 2000 Wiley-Liss, Inc.)