Well-differentiated liposarcoma/atypical lipomatous tumor and dedifferentiated liposarcoma can be difficult to distinguish from benign lipomatous neoplasms and other high-grade sarcomas, respectively. Cytogenetics in these tumors has identified ring and giant chromosomes composed of 12q13-15 amplicons including the MDM2 gene. Identifying MDM2 amplification by fluorescence in situ hybridization may prove an adjunctive tool in the diagnosis of lipomatous neoplasms. Dual color fluorescence in situ hybridization employing a laboratorydeveloped BAC label probe cocktail specific for MDM2 (12q15) and a probe for the centromeric region of chromosome 12 (Abbott Molecular, DesPlaines, IL) was performed on formalin-fixed and paraffin-embedded tissue including whole sections from atypical lipomatous tumors (n ¼ 13), dedifferentiated liposarcomas (n ¼ 14), benign lipomatous tumors (n ¼ 30), and pleomorphic sarcoma, not otherwise specified (n ¼ 10), and a tissue microarray containing a variety of high-grade sarcomas (n ¼ 63). An MDM2/chromosome 12 ratio Z2.0 was considered amplified, o2.0 nonamplified, and cases displaying 42 signals of both probes and an MDM2 ratio o2.0 polysomic for chromosome 12. Of the well-differentiated and dedifferentiated liposarcomas, 100% showed amplification of MDM2. Chromosome 12 polysomy was noted in 89% of spindle cell/pleomorphic lipomas, while all angiolipomas and lipomas were nonamplified and eusomic. MDM2 amplification was observed in 40% of pleomorphic sarcomas and a small subset of high-grade sarcomas (3/63). MDM2/chromosome 12 fluorescence in situ hybridization is a sensitive and specific tool (both 100%) in evaluating low-grade lipomatous neoplasms. The specificity decreases in high-grade sarcomas, as MDM2 amplification was observed in a small portion of pleomorphic sarcomas and high-grade sarcomas other than dedifferentiated liposarcomas. Importantly, none of the benign lipomatous lesions were MDM2 amplified and even cells in areas of well-differentiated liposarcomas with minimal cytologic atypia were amplified, making the probe a valuable tool in the diagnosis of even limited biopsy samples of well-differentiated lipomatous neoplasms.
BackgroundFascin is an actin bundling protein with roles in the formation of cell protrusions and motility of mesenchymal and neuronal cells. Fascin is normally low or absent from epithelia, but is upregulated in several epithelial neoplasms where it may contribute to an invasive phenotype. Here, we report on the prevalence and potential clinical significance of fascin expression in relation to the progression of colorectal adenocarcinoma and to tumor cell proliferation as measured by Ki67 index.MethodsConventional tissue sections of 107 colorectal adenomas and 35 adenocarcinomas were analyzed by immunohistochemistry for fascin and Ki67 expression.Fascin expression and Ki67 proliferation index were also investigated by use of a tissue microarray containing cores from a further 158 colorectal adenocarcinomas and 15 adenomas linked to a CCF, IRB-approved database with a mean of 38 months of clinical follow-up. Survival analysis was carried out by the Kaplan-Meier and Cox regression methods.ResultsFascin was not expressed by the normal colonic epithelium. In conventional sections, 16% of adenomas and 26% of adenocarcinomas showed fascin expression in greater than 10% of the tumor cells. In the clinically-annotated tumors, fascin immunoreactivity was more common in tumors located in the proximal colon (p = 0.009), but was not associated with age, gender, or TNM stage. Patients with stage III/IV adenocarcinomas (n = 62) with strong fascin immunoreactivity had a worse prognosis than patients with low or absent fascin, (3-year overall survival of 11% versus 43% for fascin-negative patients; p = 0.023). In adenomas, fascin and Ki67 tended to be inversely correlated at the cellular level; this trend was less apparent in adenocarcinomas.ConclusionFascin is upregulated in a proportion of adenomas, where its expression is often focal. Strong and diffuse expression was seen in a subset of advanced colorectal adenocarcinomas that correlated with shorter survival in stage III and IV patients. Fascin may have prognostic value as an early biomarker for more aggressive colorectal adenocarcinomas.
The UroVysion FISH assay provides high sensitivity and specificity to detect transitional cell carcinoma in cytologically equivocal and negative urine samples. These results emphasize the important role of this assay in the management of bladder cancer.
A high degree of interobserver variability is seen in the histological diagnosis of Barrett's esophagus-related LGD. Although the number of observations is low, a consensus diagnosis of LGD among GI pathologists suggests an increased risk of progression from LGD to HGD or carcinoma.
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