Purpose: Primary tumor xenografts (PTXG) established directly from patients' primary tumors in immunosuppressed animals might represent the spectrum of histologic complexity of lung cancers better than xenografts derived from established cell lines. These models are important in the study of aberrant biological pathways in cancers and as preclinical models for testing new therapeutic agents. However, not all primary tumors engraft when implanted into immunosuppressed mice. We have investigated factors that may influence the ability of primary non-small cell lung cancer (NSCLC) to form xenografts and their association with clinical outcome.Experimental Design: Tumor fragments from patients undergoing curative surgery were implanted into NOD-SCID (nonobese diabetic-severely combined immunodeficient) mice within 24 hours of surgery. Patient characteristics for tumors that engrafted (XG) and did not engraft (no-XG) were compared. Patient tumor DNA was profiled for the presence of 238 known mutations in 19 cancer-associated genes by using the MassARRAY platform.Results: Xenografts were established and passaged successfully from 63 of 157 (40%) implanted NSCLCs. Tumor factors associated with engraftment included squamous histology, poor differentiation, and larger tumor size. Significantly fewer EGFR (epidermal growth factor receptor)-mutated tumors engrafted (P ¼ 0.03); conversely, more K-RAS-mutated tumors engrafted (P ¼ 0.05). In multivariate analysis including age, sex, stage, and mutation, patients with XG tumors had significantly shorter diseasefree survival compared with no-XG patients (hazard ratio : 7.0, 95% CI: 3.1-15.81; P < 0.000003).Conclusion: PTXGs closely mirror the histology and molecular profiles of primary tumors and therefore may serve as important preclinical models. Tumors that engraft are biologically more aggressive and may be more representative of cancers with a higher propensity to relapse after surgery. Clin Cancer Res; 17(1); 134-41. Ó2010 AACR.

We hypothesize that mechanisms involved in the active suppression of viral antigens may also be involved in the suppression of tumor antigens, and may have resulted in the observed favorable clinical outcome.

Absence of PTEN protein expression is an independent prognostic marker in early-stage resected lung adenocarcinoma.

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Papillary renal cell carcinoma (PRCC) can display extensive areas of solid and non-papillary architecture and extensive areas with oncocytic cytoplasm. Eleven oncocytic renal cell neoplasms (ORCN) with histopathological features posing a diagnostic problem between renal cell carcinoma (RCC) with oncocytic features and renal oncocytoma (RO) were identified. The neoplasms were well circumscribed or encapsulated tumors with solid and diffuse growth pattern. Very occasional papillae were seen in four and tumoral necrosis in two of 11. Six ORCN displayed a CD117+/progesterone receptor (PR)+ immunophenotype (feature shared by RO) and five tumors displayed a CD117-/PR- immunophenotype (feature shared by RCC). The CD117-/PR- ORCN also displayed alpha-methylacyl-coenzyme A racemase and RCC antigen reactivity as well as varying reactivity for cytokeratin 7, vimentin and CD10 (features of oncocytic PRCC). These five cases had tumor sizes ranging from 1 to 6 cm. Two patients in the latter group developed progression of the disease with metastases. In conclusion, oncocytic PRCC with solid architecture is a rare type of RCC. The carcinoma often poses differential diagnostic problems with RO and has similar immunohistochemical properties to the common type of PRCC. Cytogenetic and molecular studies have not been performed yet for this variant of RCC.

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