Purpose:To investigate the association between parameters obtained from dynamic contrast enhanced MRI (DCE-MRI) of breast cancer using different analysis approaches, as well as their correlation with angiogenesis biomarkers (vascular endothelial growth factor and vessel density).Materials and Methods: DCE-MRI results were obtained from 105 patients with breast cancer (108 lesions). Three analysis methods were applied: 1) whole tumor analysis, 2) regional hot-spot analysis, and 3) intratumor pixel-by-pixel analysis. Early enhancement intensities and fitted pharmacokinetic parameters were studied. Paraffin blocks of 71 surgically resected specimens were analyzed by immunohistochemical staining to measure microvessel counts (with CD31) and vascular endothelial growth factor (VEGF) expression levels.Results: MRI parameters obtained from the three analysis methods showed significant correlations (P Ͻ 0.0001), but a substantial dispersion from the linear regression line was noted (r ϭ 0.72-0.97). The entire region of interest (ROI) vs. pixel population analyses had a significantly higher association compared to the entire ROI vs. hot-spot analyses. Cancer specimens with high VEGF expression had significantly higher CD31 microvessel densities than did specimens with low VEGF levels (P Ͻ 0.005). No significant association was found between MRI parameters obtained from the three analysis strategies and IHC based measurements of angiogenesis. Conclusion:A consistent analysis strategy was important in the DCE-MRI study. In this series, none of these strategies yielded results for MRI based quantitation of tumor vascularity that were associated with IHC based measurements. Therefore, different analyses could not account for the lack of association.

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On the basis of reports linking mutant p53 (mp53) to decreased expression of the angiogenesis inhibitor thrombospondin-1 (TSP-1) and increased angiogenesis, we compared primary and metastatic melanoma tumor specimens to determine if these factors were associated with metastatic progression. Western blotting, immunohistochemistry (IHC), and image analysis (IA) techniques were employed to evaluate the relationship between p53 status and TSP-1 expression in Zaz and M14 melanoma cell lines, and among p53, TSP-1, and angiogenesis in primary and metastatic melanomas. Zaz cells expressed wild-type p53 (WT p53) and high levels of TSP-1, while the M14 cells expressed mp53 and low TSP-1 levels. Examination of clinical melanoma specimens (N = 99) revealed an incidence of mp53 of 48%. Specimens with WT p53 (N = 46) expressed significantly higher mean levels of TSP-1 (41 +/- 27 vs. 21 +/- 24; p = 0.0004), and lower microvessel counts per 200x field (25 +/- 17 vs. 40 +/- 20; p = 0.0001) than tumors expressing mp53 (N = 42). A significantly higher incidence of mp53 expression was seen in metastatic tumors (64%, 37/58) than in primary tumors (27%, 11/41)(p < 0.0005). Primary tumors specimens had higher levels of TSP-1 (40 +/- 27 vs. 25 +/- 25; p = 0.0054) and lower microvessel counts (26 +/- 18 vs. 39 +/- 20, p = 0.0013) than metastatic tumors. These data suggest that acquisition of mp53, decreased TSP-1, and increased microvessel infiltration may be interrelated and associated with the metastatic phenotype in malignant melanoma.

Minimal deviation melanoma is a controversial entity encompassing a heterogeneous group of lesions cytologically in the spectrum between recognized subtypes of nevi and conventional "primary configuration" melanomas and reported to have a better prognosis than the latter. To evaluate the distinctiveness of minimal deviation melanoma, Ki-67 proliferation rates and p53 expression in minimal deviation melanomas were compared with those in compound nevi, Spitz nevi, and vertical growth phase superficial spreading malignant melanoma. Twelve examples of each lesion were immunostained with antibodies to the Ki-67 and p53 proteins and evaluated by a pathologist who was blind to the diagnoses. The mean Ki-67 (MIB-1) proliferation rates for the compound nevi, Spitz nevi, minimal deviation melanomas, and superficial spreading malignant melanomas were 0, 3%, 13%, and 25%, respectively. The mean Ki-67 proliferation rate was statistically greater in the minimal deviation melanomas than in the compound nevi or the Spitz nevi (P < .05), but the proliferation rates in the two melanoma subtypes were not statistically significant (P ‫؍‬ .08). The mean p53 values for these lesions were 0, 9%, 9%, and 26%, respectively; the latter two were statistically different (P < .01). Based on these Ki-67 and p53 immunophenotypes, minimal deviation melanoma may represent a distinct entity. In a busy dermatopathology practice, there are seen rare and unusual forms of nevomelanocytic proliferations that do not conform to generally recognized nevus or melanoma classifications. Placement of these problematic lesions into benign or malignant categories is difficult, and terms such as melanocytic tumor of undetermined malignant potential (1) or atypical melanocytic proliferation have been developed to communicate this prognostic uncertainty. Along these lines, the classification of minimal deviation melanoma (2) was developed for a subset of such tumors, composed of a monotonous cell population, that were more atypical than ordinary nevi but less atypical than conventional melanomas. A minimal deviation melanoma architecturally consists of an expansive nodule in the vertical growth phase that fills the papillary dermis and often extends into the reticular dermis (Fig. 1). The tumors are further classified, based on the cytologic characteristics, into subtypes such as a Spitz variant, a halo nevus-like variant, a pigmented spindle cell variant, a desmoplastic variant, a small cell variant, and a dermal variant. Minimal deviation melanomas have been associated with a better prognosis (2). As with other attempts to deal with these rare and difficult melanocytic neoplasms, this classification remains controversial (3) and has not been uniformly accepted in the dermatopathology community. This study seeks to evaluate the distinctiveness of minimal deviation melanoma by comparing Ki-67 proliferation rates and p53 expression in minimal deviation melanomas with those in compound