Is tail vein injection a relevant breast cancer lung metastasis model?

BACKGROUND: TWO MOST COMMONLY USED ANIMAL MODELS FOR STUDYING BREAST CANCER LUNG METASTASIS ARE: lung metastasis after orthotopic implantation of cells into the mammary gland, and lung implantations produced after tail vein (TV) injection of cells. Tail vein injection can produce lung lesions faster, but little has been studied regarding the differences between these tumors, thus, we examined their morphology and gene expression profiles. METHODS: Syngeneic murine mammary adenocarcinoma, 4T1-luc2 cells, were implanted either subcutaneously (Sq), orthotopically (OS), or injected via TV in Balb/c mice. Genome-wide microarray analyses of cultured 4T1 cells, Sq tumor, OS tumor, lung metastases after OS (LMet), and lung tumors after TV (TVt) were performed 10 days after implantation. RESULTS: Bioluminescence analysis demonstrated different morphology of metastases between LMet and TVt, confirmed by histology. Gene expression profile of cells were significantly different from tumors, OS, Sq, TVt or LMet (10,350 probe sets; FDR≤1%; P<0.0001). Sq tumors were significantly different than OS tumors (700 probe sets; FDR≤15%; P<0.01), and both tumor types (Sq and OS) were significantly different than LMet (1,247 probe sets; >1.5-fold-change; P<0.01), with no significant difference between TVt and LMet. CONCLUSIONS: There were significant differences between the gene profiles of cells in culture and OS versus LMet, but there were no differences between LMet versus TVt. Therefore, the lung tumor generated by TVt can be considered genetically similar to those produced after OS, and thus TVt is a relevant model for breast cancer lung metastasis.

Clinical verification of the performance of the pathwork tissue of origin test: utility and limitations.

Gene expression-based assays have been introduced into the clinical arena to assist in the diagnosis of poorly differentiated or undifferentiated tumors. The US Food and Drug Administration has cleared the microarray-based Pathwork Tissue of Origin (TOO) Test (Pathwork Diagnostics, Sunnyvale, CA) for the molecular characterization of such challenging specimens. We aimed at verifying the analytic and clinical performance of this test on 43 poorly differentiated and undifferentiated tumor samples, including 6 off-panel cases and 7 cancers of unknown primary (CUP). Our results showed 97% (95% confidence interval, 80.4%-99.8%) agreement between the Pathwork TOO Test result and the complete diagnosis, which included clinical correlations and immunohistochemical staining, after the original diagnosis. We concluded that for off-panel and CUP samples, the tissue type and the cell type may be confounded by the Pathwork TOO Test and that careful clinicopathologic assessment is needed when interpreting results from this helpful ancillary tool for pathologists.

Prognostic variables and surgical management of foot melanoma: review of a 25-year institutional experience.

Introduction. Cutaneous foot melanoma is rare, challenging to manage, and not adequately examined in the literature. This study evaluated the prognostic variables and surgical management of foot melanoma. Materials and Methods. Foot melanoma cases managed at an academic center from 1985 to 2010 were retrospectively reviewed. Results. 46 patients were identified with a broad range of demographic characteristics. Overall recurrence was 32.6%: 19% acral lentiginous, 57% nodular, 66% superficial spreading, 30% melanoma unspecified, 50% severely atypical; 53% ulcerated, 23% nonulcerated; 29% on the dorsum of the foot, 17% heel, 60% ankle, 22% toe, 50% plantar; 0% <1 mm thick, 47% 1-4 mm, 33% >4 mm. 13 had positive nodes, 4 (31%) of whom recurred. Prognostic factors and recurrence did not correlate, and survival was 96% with a median followup of 91 months. Conclusions. Aggressive management of foot melanoma may result in excellent long-term survival even following disease recurrence.