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The use of hygroscopic sonographically detectable clips (HSDCs) has dramatically increased during the last years, especially in breast cancer patients who undergo neoadjuvant chemotherapy. The aims of this study are to define the appearance of HSDC sites in histopathological specimens, and to enable pathologists to recognize these sites and differentiate them from other lesions. We examined 124 breast cancer specimens in which the application of HSDCs was documented, 88 breast tissues and 36 lymph nodes, and analyzed the appearance of the clip site in these tissues. The clip site was clearly detected histologically in 79/88 (90%) of the breast specimens and in 29/36 (81%) of lymph node specimens. In most of the specimens, the HSDC site had a specific characteristic appearance of a pseudocyst, lined by layers of epithelioid histiocytes, sometimes with pseudopapillary formation, and with minimal or no fibrosis. This was the appearance in 69 of the breast specimens and in 23 of the lymph node specimens. In other specimens, scarring, scattered foamy macrophages and abundant siderophages were the predominant findings, as usually found in sites of other clips. As non-palpable breast lesions become more frequent, clips play a major role in the treatment of breast cancer, making them an important component of the communication among radiologists, surgeons, pathologists, and oncologists. HSDCs in tissues have a characteristic appearance with an epithelioid component. Pathologists should be able to recognize this finding, differentiate it from other breast lesions and include it in the pathology report.

Fyn kinase is implicated in prostate cancer. We illustrate the role of miR-125a-3p in cellular pathways accounted for motility and migration of prostate cancer cells, probably through its regulation on Fyn expression and Fyn-downstream proteins. Prostate cancer PC3 cells were transiently transfected with empty miR-Vec (control) or with miR-125a-3p. Overexpression of miR-125a-3p reduced migration of PC3 cells and increased apoptosis. Live cell confocal imaging indicated that overexpression of miR-125a-3p reduced the cells' track speed and length and impaired phenotype. Fyn, FAK and paxillin, displayed reduced activity following miR-125a-3p overexpression. Accordingly, actin rearrangement and cells' protrusion formation were impaired. An inverse correlation between miR-125a-3p and Gleason score was observed in human prostate cancer tissues. Our study demonstrated that miR-125a-3p may regulate migration of prostate cancer cells.

Objectives High-grade nonmuscle-invasive urothelial tumors of the bladder that fail intravesical Bacillus Calmette-Guerin (BCG) immunotherapy are at the highest risk of progression. Initial evidence links heat shock protein expression levels and outcome of bladder cancer after BCG treatment. We aimed to determine the association between HSP60, 70, and 90 expression levels and long-term outcomes of T1 high-grade (T1HG) urothelial bladder tumors treated with BCG immunotherapy. Materials and Methods Data of 54 consecutive patients with primary T1HG bladder tumors who underwent transurethral resection between 2002 and 2008 and received at least an induction course of BCG were reviewed. Immunohistochemical staining for heat shock protein (HSP)60, 70, and 90 were performed on resected specimens. Study outcomes included disease recurrence and progression. The association between HSP expression levels and outcomes were evaluated with univariable and multivariable Cox proportional hazards models. Results During a median follow-up of 9.6 years, 25 patients had a disease recurrence and 14 patients a disease progression. Estimated 5-year recurrence and progression-free survival were 59% and 81%, respectively. On multivariable analyses, HSP60 staining >65% was associated with a higher risk for progression (hazard ratio [HR] = 3.96, 95% confidence interval [CI] 1.35–11.58, P = 0.012), and HSP70 staining >5% was associated with a decreased risk for progression (HR = 0.33, 95% CI 0.11–0.98, P = 0.045), and recurrence (HR = 0.29, 95% CI 0.13–0.65, P = 0.003). HSP90 expression was not associated with disease recurrence or progression. Five patients had both a HSP60 staining >65% and a HSP70 staining ≤5% all of whom recurred at a median time of 6 months (interquartile range 3, 16) and 80% of whom progressed at a median time of 26 months (interquartile range 5, 60). Conclusions HSP60 and 70 cellular expression levels are associated with long-term outcome following BCG treatment of T1HG urothelial bladder tumors. These findings, if further validated, may be used to better stratify the risk of disease recurrence and progression in this group of patients.

The detection of breast carcinoma cells in effusions is associated with rapidly fatal outcome, but these cells are poorly characterized at the molecular level. This study compared the gene array signatures of breast carcinoma cells in primary carcinomas and effusions. The genetic signature of 10 primary tumors and 10 effusions was analyzed using the Array-Ready Oligo set for the Human Genome platform. Results for selected genes were validated using PCR, Western blotting, and immunohistochemistry. Array analysis identified 255 significantly downregulated and 96 upregulated genes in the effusion samples. The majority of differentially expressed genes were part of pathways involved in focal adhesion, extracellular matrix-cell interaction, and the regulation of the actin cytoskeleton. Genes that were upregulated in effusions includedKRT8, BCAR1, CLDN4, VIL2, whileDCN, CLDN19, ITGA7, andITGA5were downregulated at this anatomic site. PCR, Western blotting, and immunohistochemistry confirmed the array findings forBCAR1, CLDN4, VIL2, andDCN. Our data show that breast carcinoma cells in primary carcinomas and effusions have different gene expression signatures, and differentially express a large number of molecules related to adhesion, motility, and metastasis. These differences may have a critical role in designing therapy and in prognostication for patients with metastatic disease localized to the serosal cavities.

Background: Renal cancers account for more than 3% of adult malignancies and result in more than 13,000 deaths per year in the US alone. The four most common types of kidney tumors include the malignant renal cell carcinomas: clear cell, papillary and chromophobe, as well as the benign oncocytoma. These histological subtypes vary in their clinical course and their prognosis, and different clinical strategies have been developed for their management. The differential diagnosis between the subtypes of kidney tumors based on morphology alone can be challenging, and is subjected to inter- and intra-observer variability. Even when utilizing immunohistochemistry (IHC) markers, the ability to differentiate between sub-types can be difficult, especially in the setting of uncommon morphology and biopsy sample with small amounts of tumor tissue. We present the development and validation of a microRNA-based test for classifying primary kidney tumors. Methods: 181 Formalin Fixed Paraffin Embedded (FFPE) samples from primary kidney tumors were collected and reviewed by pathologists from different institutes according to morphology and available IHC labeling data. High-quality total RNA, including the well-preserved microRNA fraction, was extracted from the FFPE samples using a proprietary protocol. Expression levels of hundreds of microRNAs were profiled using a custom microarray platform. Technical validation of the array results was performed using qRT-PCR. A diagnostic assay was developed using a K-nearest neighbor algorithm that searches for the 5 samples in the training database (181 samples used for assay development) that are most similar to the tested sample. The result for the tested sample is defined by a majority vote of the pre-determined subtypes of these 5 closest neighbors. A validation set of 201 independent samples was classified using the assay and analyzed blindly. Results: A set of 24 differentially expressed microRNAs were found to separate the four kidney tumor subtypes and were chosen as classifiers in the KNN algorithm. Clinical validation was performed using an independent, blinded sample set. The test was able to produce results for 92% of the validation set of 201 samples with accuracy of 95%. Conclusions: Expression levels of 24 microRNAs measured on a microarray platform were found to accurately differentiate the four main types of primary kidney tumors. These findings were the basis for the development and validation of a standardized diagnostic assay for the classification of renal cell tumors in FFPE samples from resections or biopsies. This assay can serve as a reliable diagnostic tool to aid physicians with the growing unmet need for kidney tumor classification. Citation Format: Robert Wassman, Brianna St. Cyr, Eddie Fridman, Iris Barshack, Yajue Huang, Sofia Zilber, Mats Sanden, Hila Benjamin, Noga Yerushalmi, Yael Spector. Development and validation of a microRNA-based diagnostic assay for the classification of renal cell tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 802. doi:10.1158/1538-7445.AM2013-802