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BACKGROUND: Human tumors transplanted into immunodeficient mice (xenografts) are good preclinical models, and it is important to identify possible systematic changes during establishment and passaging in mice. METHODS: High-resolution microarray-based comparative genomic hybridization (array CGH) was used to investigate how well a series of sarcoma xenografts, including 9 patient/xenograft pairs and 8 early versus late xenograft passage pairs, represented the patient tumor from which they originated. RESULTS: In all analyses, the xenografts were more similar to their tumor of origin than other xenografts of the same type. Most changes in aberration patterns were toward a more normal genome complement, and the increased aberrations observed were mostly toward more loss. In general, the changes were scattered over the genome, but some changes were significant in osteosarcomas. These were rather focused and consistent with amplifications frequent in patient samples, involving the genes platelet-derived growth factor receptor A (PDGFRA), cysteine-rich hydrophobic domain 2 (CHIC2), FIP-like 1 (FIP1L1), ligand of numb-protein X1 (LNX1), RAS-like family 11 member B (RASL11B), and sec1 family domain containing 2 (SCFD2), probably a sign of continued tumor progression. Some changes that disappeared may have been involved in host-stroma interactions or chemotherapy resistance, possibly because of the absence of selection in the mouse. CONCLUSIONS: Direct xenografts reflected well the genomic patterns of their tumors of origin. The few significant aberrations that were lost during passaging in immune-defective mice may have been caused by the lack of selection in the new host, whereas aberrations that were gained appeared to be the result of general tumor progression rather than model-specific artifacts. Cancer 2011;. © 2011 American Cancer Society.

BACKGROUND. The objective of this study was to compare the prognostic relevance of Response Evaluation Criteria in Solid Tumors (RECIST) versus Choi criteria for the assessment of response in patients with high-risk soft tissue sarcoma of the extremities or trunk wall who received preoperative chemotherapy with or without radiotherapy in a phase 3 trial. METHODS. Patients received 3 cycles of preoperative epirubicin þ ifosfamide with or without radiotherapy. The diagnostic concordance between RECIST and Choi criteria and their correlation with overall survival (OS) and freedom from progression (FFP) were evaluated in a univariate Cox regression model. RESULTS. In 243 of 321 eligible patients, RECIST, Choi criteria, and histology were predictive for OS and FFP. In the subgroup of 69 patients who received chemotherapy alone and were evaluable by both RECIST and Choi criteria, Choi criteria were associated significantly with OS and FFP, whereas RECIST predicted only FFP, and the pattern of agreement observed between the 2 criteria was unsatisfactory. On a dichotomous scale, comparing objective response (complete and partial responses) and lack of response (stable and progressive disease) to preoperative chemotherapy according to RECIST and Choi criteria, only Choi criteria were predictive of OS and FFP, and fair agreement between RECIST and Choi criteria was observed. When lack of progression and progression were compared (complete and partial responses þ stable disease vs progressive disease), both assessment criteria were significantly predictive of OS and FFP, and there was substantial agreement between the 2 criteria. CONCLUSIONS. Response to chemotherapy with or without radiotherapy was associated with a better outcome in patients with high-risk soft tissue sarcoma. Choi criteria were better predictors than RECIST in patients who received preoperative chemotherapy alone. Cancer 2012;118:5857-66. V C 2012 American Cancer Society.

Human tumors transplanted into immunodeficient mice (xenografts) are good preclinical models, and it is important to identify possible systematic changes during establishment and passaging in mice.High-resolution microarray-based comparative genomic hybridization (array CGH) was used to investigate how well a series of sarcoma xenografts, including 9 patient/xenograft pairs and 8 early versus late xenograft passage pairs, represented the patient tumor from which they originated.In all analyses, the xenografts were more similar to their tumor of origin than other xenografts of the same type. Most changes in aberration patterns were toward a more normal genome complement, and the increased aberrations observed were mostly toward more loss. In general, the changes were scattered over the genome, but some changes were significant in osteosarcomas. These were rather focused and consistent with amplifications frequent in patient samples, involving the genes platelet-derived growth factor receptor A (PDGFRA), cysteine-rich hydrophobic domain 2 (CHIC2), FIP-like 1 (FIP1L1), ligand of numb-protein X1 (LNX1), RAS-like family 11 member B (RASL11B), and sec1 family domain containing 2 (SCFD2), probably a sign of continued tumor progression. Some changes that disappeared may have been involved in host-stroma interactions or chemotherapy resistance, possibly because of the absence of selection in the mouse.Direct xenografts reflected well the genomic patterns of their tumors of origin. The few significant aberrations that were lost during passaging in immune-defective mice may have been caused by the lack of selection in the new host, whereas aberrations that were gained appeared to be the result of general tumor progression rather than model-specific artifacts.

The morphology and clinical outcome of 30 patients with malignant small round cell tumors located in the thoracopulmonary region (Askin tumor) are reported. Histologically, all tumors had similar patterns, with small round-to-oval cells and a lobulated stroma. Immunohistochemical analysis always resulted in positive staining for one or several neural markers. No significant differences were found compared with the immunomarkers in 26 typical Ewing's sarcomas located outside the thoracic wall. In three specimens, electron microscopy confirmed the presence of membrane-bound neurosecretory granules. It was confirmed that there is a remarkable similarity among all malignant small round cell tumors, including Askin tumor and Ewing's sarcoma. Overall survival was poor with a 2-year rate of 38% and a 6-year rate of 14%.

BACKGROUND The differential expression patterns of cytokeratin 20 (CK20) and 34βE12 antigen in low-grade papillary urothelial tumors of the bladder are discussed. METHODS A retrospective study of 120 patients with low-grade papillary bladder tumors (45 neoplasms of low malignant potential and 75 low-grade WHO G1 carcinomas) was performed. All tumors were graded in accordance with the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) and 1999 WHO classifications. The mean follow-up was 76.6 months (range, 36–168 mos), considering for prognostic purposes the time to first recurrence, or relapse-free interval (RFI), and the total number of recurrent patients. Immunohistochemically, normal or abnormal CK20 and 34βE12 antigen expression patterns were determined for each patient. CK20 (clone IT-Ks) and a high-molecular weight cytokeratin (clone 34βE12) were the monoclonal antibodies used in the immunohistochemical study. RESULTS Seventy-seven of 120 patients (64.2%) experienced a recurrence during follow-up. In recurrence prediction, the differential expression pattern of both cytokeratins showed a high sensitivity (76.6% for CK20 and 80.5% for 34βE12 antigen) and a high positive predictive value (85.5% for CK20 and 75.6% for 34βE12 antigen), although specificity was higher for CK20 (76.7%) than it was for 34βE12 antigen (53.4%). Independent of adjuvant intravesical chemotherapy, these 2 markers showed a strong statistical correlation (p < 0.001) in univariate studies with both the prediction of disease recurrences and RFI. CONCLUSIONS CK20 and 34βE12 antigen have proved to be strong predictive markers of disease recurrences when considering different topographic expression profiles, and, in the authors' opinion, these profiles could be incorporated into follow-up clinicopathologic strategies. Cancer 2003;97:1876–83. © 2003 American Cancer Society. DOI 10.1002/cncr.11265

BACKGROUND In vitro, tissue culture-associated differentiation assays have facilitated the identification of multiple tumor-cell types. METHODS We have investigated the capability of differentiation of three extraosseous Ewing's sarcoma cell lines toward a neural and muscular direction by in vitro stimulation with dibutyryl cyclic adenosine-monophosphate (db cAMP) and 5-azacytidine, respectively. RESULTS Elongation of cytoplasmic processes and increase of neural markers chromogranin, S-100 protein, and glial fibrillary acidic protein were observed after db cAMP treatment of these lines and neurosecretory granules as well as myelin figures were demonstrated ultrastructurally. These results support the existence of several pathways of neural differentiation in vitro--neuroblastic, Schwannian, and central glial--in stages of maturation more advanced than those previously reported in Ewing's sarcoma of bone. The cell lines showed no definitive myoblastic differentiation after 5-azacytidine treatment. CONCLUSIONS These data suggest that these three extraosseous Ewing's sarcoma cell lines configurate a heterogeneous group of tumors with respect to capability of differentiation into the neural lineage, arrested at more advanced stages of neural crest development than Ewing's sarcoma of bone and without capability of myoblastic differentiation with 5-azacytidine.

This study characterizes the histogenesis of soft tissue Ewing’s sarcoma (StEs) based upon an analysis of three tumors. Long-term cultured cell lines and nude mice xenografts were established from original neoplasms or from their metastases. Histologically they revealed a small round cell pattern without signs of differentiation. Several ultrastructural features of neural type were found; the same were also seen on culture cell lines. Moreover, immunohistochemical study for neural markers revealed the presence of HNK-1, NSE, LIRC-LON 36, S-100 protein, glial fibrillary acidic protein, neurofilaments (70 kilodaltons), and chromogranin; some of these markers were present only in the transplants. Cytokeratin was also seen. The translocation t(11;22)(q24;q12) was found in all three neoplasms together with other chromosomal abnormalities. N-myc RNA gave negative results whereas c-myc RNA was expressed. Therefore it may be postulated that StEs displays neuroectodermal features somewhat similar to those seen in peripheral neuroepithelioma as well as in atypical Ewing’s sarcoma of bone. Cancer 66:2589-2601,1990.

The authors present 611 and 262 case histories of patients with breast cancer, studied 5 and 10 years after mastectomy, respectively; 27 clinical and 10 histologic parameters were considered for the statistical evaluation, in order to define an Individualized Prognostic Index (IPI) for breast cancer survivability. The probability of survival was estimated by a Bayesian formula using selected prognostic parameters, these parameters were placed in order of discriminant resolution and, for the calculation of the IPI, were selected according to their importance, as it follows: 5 years after surgery: percent affected nodules, dermal infiltration, TNM phase, Scarff-Bloom index and evolutive outbreak (PEV); 10 years after surgery: TNM phase, dermal infiltration, percent affected nodules and Scarff-Bloom index. The current information considers that out of several parameters, the selected prognostic parameters used for the IPI are sufficient to establish probability tests and a reliable estimation of life expectancy following breast cancer surgery.

Ewing's sarcoma (ES) of bone may occasionally display rosette-like textures mimicking Homer-Wright ones, as seen in neuroectodermic neoplasms (neuroblastoma, peripheral neuroepithelioma). Of a group of 39 cases of ES, reviewed with electron microscopic study, the authors have isolated five atypical ES, which histologically also possessed neuroectodermic traces. These tumors were composed of small round blue cells with rosette-like figures and cytoplasmic glycogen. The immunohistochemical analysis showed positivity for neuron-specific enolase (NSE) as well as for HNK-1 (leu-7) monoclonal antibody. Electron microscopic examination confirmed the tumor cell as being of small round type, with a dense chromatine pattern and the presence of isolated dendritic processes, as well as synaptic-like buttons; intermediate filaments, neurotubuli, and dense-core neurosecretory granules also were seen. Moreover, in two cases basement-like condensations surrounded some cells. Scanning electron microscopic study in one case confirmed the presence of rosette-like figures and cell elongations with short dendritic projections of the cytoplasm. Clinically and radiologically these cases showed features similar to ES of bone; one case, located in the chest wall, had a local relapse after treatment, with the histologic features of a pleomorphic neuroblastoma. The authors conclude that these tumors resemble closely immature neuroepithelioma of soft tissue but, being primary to bone, are superimposable on those described as "neuroectodermal tumors of bone."