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Combined small-cell carcinoma and squamous cell carcinoma of the larynx is an exquisitely rare and underreported primary tumor the head and neck region, with an English literature review revealing only 17 documented cases. There is limited information on how best to treat these patients oncologically, given the low number of reported cases. A subset of the reported cases also detail a unique local spread of this combined carcinoma, further obscuring the clinical picture of these patients. Here, we detail an 18th case, with nodal metastasis of only one component of the primary tumor, and discuss the published literature surrounding this etiology. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis is a key event in the progression of breast cancer. Therefore it is important to understand the underlying mechanisms which facilitate regional lymph node metastatic progression. Methodology/Principal Findings: We performed gene expression profiling of purified tumor cells from human breast tumor and lymph node metastasis. By microarray network analysis, we found an increased expression of polycomb repression complex 2 (PRC2) core subunits EED and EZH2 in lymph node metastatic tumor cells over primary tumor cells which were validated through real-time PCR. Additionally, immunohistochemical (IHC) staining and quantitative image analysis of whole tissue sections showed a significant increase of EZH2 expressing tumor cells in lymph nodes over paired primary breast tumors, which strongly correlated with tumor cell proliferation in situ. We further explored the mechanisms of PRC2 gene up-regulation in metastatic tumor cells and found up-regulation of E2F genes, MYC targets and downregulation of tumor suppressor gene E-cadherin targets in lymph node metastasis through GSEA analyses. Using IHC, the expression of potential EZH2 target, E-cadherin was examined in paired primary/lymph node samples and was found to be significantly decreased in lymph node metastases over paired primary tumors. Conclusions/Significance: This study identified an over expression of the epigenetic silencing complex PRC2/EED-EZH2 in breast cancer lymph node metastasis as compared to primary tumor and its positive association with tumor cell proliferation in situ. Concurrently, PRC2 target protein E-cadherin was significant decreased in lymph node metastases, suggesting PRC2 promotes epithelial mesenchymal transition (EMT) in lymph node metastatic process through repression of E-cadherin. These results indicate that epigenetic regulation mediated by PRC2 proteins may provide additional advantage for the outgrowth of metastatic tumor cells in lymph nodes. This opens up epigenetic drug development possibilities for the treatment and prevention of lymph node metastasis in breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To utilize a novel circulating tumor cell (CTC) technology to quantify ERCC1 expression on CTCs and determine whether ERCC1 expression levels predict efficacy of platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). Experimental design: ERCC1 expression was measured in 17 metastatic NSCLC patients who received platinum-based therapy and had ≥2 intact CTCs with acceptable ERCC1 expression assay results. ERCC1 levels were determined from average expression on individual CTCs in each sample. Progression-free survival (PFS) was calculated from the date of therapy initiation. Results: PFS decreased with increasing ERCC1 expression (p <0.04, F-test, linear regression). Lack of ERCC1 expression was associated with longer PFS (266 days versus 172 days, log-rank, p <0.02) in a Kaplan–Meier analysis using ERCC expression level of 1 as a cutoff (range 0–30). The difference in survival was statistically significant with a hazard ratio of 4.20 (95% CI 1.25–14.1, p <0.02, log-rank). PFS was also observed to decrease with increased cytokeratin (CK) expression (p <0.01 long-rank (Cox regression) and F-test (linear regression)). The hazard ratio is 4.38 (95% CI 1.76–10.9) for each log-change in CK value until progression was noted on imaging. Conclusion: Low expression of ERCC1 on CTCs correlates with PFS in patients with metastatic NSCLC receiving platinum-based therapy. [Copyright &y& Elsevier]