Esthesioneuroblastoma (ENB) is derived from the specialized olfactory neuroepithelium. Hyams grading and Kadish staging have been used to prognosticate and to guide treatment decisions. In this study, we sought to validate the prognostic utility of these systems in a large ENB cohort. We retrospectively analyzed the records of patients with ENB who had been evaluated and treated at our institution. The association of grade and stage with prognostic outcome was assessed; the Kaplan–Meier estimator was used to generate 5-year OS and DFS curves. Out of 124 cases we identified, 121 were assessed for grading and 109 for staging. Review of the tissue samples revealed that 62 % of tumors were low grade (I/II) and 21 % were high grade (III/IV); 17 % of tumors were metastasis. The OS rate was 75 % at 5 years. The DFS was 60 % at 5 years. The OS was significantly worse for metastatic ENB (low-grade ENB vs metastatic ENB p = 0.01598); the DFS was significantly worse for high grade versus low grade ENB. Of the 109 cases that had been staged, 16 % were stage A, 33 % stage B, 43 % stage C, and 8 % stage D. In the A, B, and C groups, there were no significant differences between recurrence, distant metastasis, or 5-year survival rates. Statistical significance was not reached with the T, N, M and overall staging system. Age cutoff of 65 years reliably predicted OS. High grade of ENB was significantly associated with poor outcome, while advanced stage was not associated with poor outcome in this large cohort. Grading should certainly be considered in prognostication and treatment decisions for ENB.

Background: The patient-derived xenograft (PDX) model is likely to reflect human tumor biology more accurately than cultured cell lines because human tumors are implanted directly into animals; maintained in an in vivo, three-dimensional environment; and never cultured on plastic. PDX models of head and neck squamous cell carcinoma (HNSCC) have been developed previously but were not well characterized at the molecular level. HNSCC is a deadly and disfiguring disease for which better systemic therapy is desperately needed. The development of new therapies and the understanding of HNSCC biology both depend upon clinically relevant animal models. We developed and characterized the patient-derived xenograft (PDX) model because it is likely to recapitulate human tumor biology. Methods: We transplanted 30 primary tumors directly into mice. The histology and stromal components were analyzed by immunohistochemistry. Gene expression analysis was conducted on patient tumors and on PDXs and cell lines derived from one PDX and from independent, human tumors. Results: Five of 30 (17%) transplanted tumors could be serially passaged. Engraftment was more frequent among HNSCC with poor differentiation and nodal disease. The tumors maintained the histologic characteristics of the parent tumor, although human stromal components were lost upon engraftment. The degree of difference in gene expression between the PDX and its parent tumor varied widely but was stable up to the tenth generation in one PDX. For genes whose expression differed between parent tumors and cell lines in culture, the PDX expression pattern was very similar to that of the parent tumor. There were also significant expression differences between the human tumors that subsequently grew in mice and those that did not, suggesting that this model enriches for cancers with distinct biological features. The PDX model was used successfully to test targeted drugs in vivo. Conclusion: The PDX model for HNSCC is feasible, recapitulates the histology of the original tumor, and generates stable gene expression patterns. Gene expression patterns and histology suggested that the PDX more closely recapitulated the parental tumor than did cells in culture. Thus, the PDX is a robust model in which to evaluate tumor biology and novel therapeutics.

Adenoid cystic carcinoma (ACC), the second most frequent malignancy of the major and minor salivary glands, comprise of approximately 15-23% of all carcinomas at these locations. ACC is uniquely formed of dual epithelial and myoepithelial cells that give rise to different phenotypic patterns. We hypothesize that the dual myoepithelial/ epithelial composition of ACCs underlie their biological heterogeneity and may impact on their therapeutic management. A recurrent reciprocal translocation of t(6;9)(q22-23;p23-24) resulting in fusion gene partners comprising MYB gene the transcription factor NFIB has been reported in ACC of breast, salivary, lachrymal and ceruminal glands. In fusion positive and a subset of fusion negative ACCs, high expression of the transcript Myb was found.However, the role of Myb protein expression and the potential effect on the downstream targets have not been investigated. To investigate the biological and prognostic significance of use of elevated levels of Myb and its downstream t...