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Immunohistochemical detection of WT1 protein in a variety of cancer cells.

WT1 was first identified as a tumor suppressor involved in the development of Wilms' tumor. Recently, oncogenic properties of WT1 have been demonstrated in various hematological malignancies and solid tumors. Because WT1 has been identified as a molecular target for cancer immunotherapy, immunohistochemical detection of WT1 in tumor cells has become an essential part of routine practice. In the present study, the expression of WT1 was examined in 494 cases of human cancers, including tumors of the gastrointestinal and pancreatobiliary system, urinary tract, male and female genital organs, breast, lung, brain, skin, soft tissues and bone by immunohistochemistry using polyclonal (C-19) and monoclonal (6F-H2) antibodies against WT1 protein. Staining for C-19 and 6F-H2 was found in 35-100 and 5-88% of the cases of each kind of tumor, respectively. WT1-positive tumors included tumor of the stomach, prostate, and biliary and urinary systems, and malignant melanomas. A majority of the positive cases showed diffuse or granular staining in the cytoplasm, whereas ovarian tumors and desmoplastic small round cell tumors frequently showed nuclear staining. Glioblastomas, some of soft tissue sarcomas, osteosarcomas, and malignant melanomas of the skin showed extremely strong cytoplasmic staining as compared with other tumors. Western blot analysis showed that WT1 protein was predominantly expressed in the cytoplasm of the tumor cells in two cases of lung adenocarcinoma, supporting the intracytoplasmic staining for WT1 using immunohistochemistry. Immunohistochemical detection with routinely processed histologic sections could provide meaningful information on the expression of WT1 in cancer cells.

Adolescent↗

Malignant tumor formation in dogs previously irradiated for acanthomatous epulis.

In this retrospective study of 57 dogs irradiated for oral acanthomatous epulis, 2 (3.5%) dogs developed a second tumor (sarcoma, osteosarcoma) in the radiation treatment field at 5.2 and 8.7 years after the end of radiation therapy. As opposed to previous reports, no second epithelial tumors developed in the radiation treatment field. There is a risk of radiation-induced carcinogenesis, but it appears that it is a relatively low risk and an event that occurs years after radiation therapy. Radiation-induced tumors are of more concern in younger dogs that undergo radiation therapy for tumors that are radioresponsive, such as acanthomatous epulis, where long-term survival is expected. The only statistically significant variable in the survival analysis was age, with dogs less than 8.3 years old having a significantly longer median overall survival (2322 days) than dogs older than 8.3 years (1106 days; P<0.0001).

Animals↗

Tumoral calcinosis: pearls, polemics, and alternative possibilities.

Massive periarticular calcinosis of the soft tissues is a unique but not rare radiographic finding. On the contrary, tumoral calcinosis is a rare familial disease. Unfortunately, the term tumoral calcinosis has been liberally and imprecisely used to describe any massive collection of periarticular calcification, although this term actually refers to a hereditary condition associated with massive periarticular calcification. The inconsistent use of this term has created confusion throughout the literature. More important, if the radiologist is unfamiliar with tumoral calcinosis or disease processes that mimic this condition, then diagnosis could be impeded, treatment could be delayed, and undue alarm could be raised, possibly leading to unwarranted surgical procedures. The soft-tissue lesions of tumoral calcinosis are typically lobulated, well-demarcated calcifications that are most often distributed along the extensor surfaces of large joints. There are many conditions with similar appearances, including the calcinosis of chronic renal failure, calcinosis universalis, calcinosis circumscripta, calcific tendonitis, synovial osteochondromatosis, synovial sarcoma, osteosarcoma, myositis ossificans, tophaceous gout, and calcific myonecrosis. The radiologist plays a critical role in avoiding unnecessary invasive procedures and in guiding the selection of appropriate tests that can result in a conclusive diagnosis of tumoral calcinosis.

Calcinosis↗

Burkitt's lymphoma in the appendicular skeleton.

Of 290 Ugandan children and adolescents with proven Burkitt's lymphoma 11 had lesions in the long bones or the pelvis. These started in the medulla as small osteolytic foci which coalesced and penetrated the cortex causing subperiosteal new bone formation in layers or spicules, and giving rise to large soft-tissue masses. Common sites were the femoral and tibial diaphyses and the metaphyses around the knee. Five were in the epiphyses. Other sites were the pelvis, humerus and ulna. One patient had a lymphomatous synovial effusion of the knee. In the lower limbs the lesions were often bilateral and symmetrical. Five patients had pathological fractures. Radiologically the lesions mimicked Ewing's sarcoma, osteosarcoma, osteomyelitis, acute leukaemia, syphilis and yaws, but clinically they were relatively painless, an important differential diagnostic feature. In the five patients with sustained remissions after chemotherapy the lesions and fractures healed well and the growth plates were undamaged.

Adolescent↗

Autologous hematopoietic stem cell transplantation for pediatric solid tumors.

While advances in the treatment of pediatric cancers have increased cure rates, children with metastatic or recurrent solid tumors have a dismal prognosis despite initial transient responses to therapy. Autologous hematopoietic stem cell transplantation takes advantage of the steep dose-response relationship observed with many chemotherapeutic agents. While clearly demonstrated to improve outcomes in patients with metastatic neuroblastoma, autologous hematopoietic stem cell transplantation is also frequently used to treat patients with other high-risk diseases such as Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, Wilms' tumor, retinoblastoma, germ cell tumors, lymphomas and brain tumors. Most published experience consists of retrospective, single-arm studies; randomized clinical trials are lacking, due in part to the rarity of pediatric cancers treatable by autologous hematopoietic stem cell transplantation. These published literature demonstrate that autologous hematopoietic stem cell transplantation results in most cases in equivalent or superior outcomes when compared with conventional therapies. However, patient heterogeneity, patient selection, graft characteristics and processing and the varied conditioning regimens are additional factors to consider. Since the inception of autologous hematopoietic stem cell transplantation, regimen-related toxicity has markedly decreased and the vast majority of treatment failures are now due to disease recurrence. Prospective clinical trials are needed to identify specific high-risk patient populations, with randomization (when possible) to compare outcomes of patients undergoing autologous hematopoietic stem cell transplantation with those receiving standard therapy. In addition, investigators need to better define the role of autologous hematopoietic stem cell transplantation in these solid tumors, particularly in combination with other therapeutic modalities such as immunotherapy and novel cell processing methodologies.

Child↗

Carcinogenicity and chronic toxicity of para-chloronitrobenzene in rats and mice by two-year feeding.

Carcinogenicity and chronic toxicity of para-chloronitrobenzene (p-CNB) were examined by feeding diets containing p-CNB to rats and mice of both sexes for two years. The dietary concentration of p-CNB was 0 (control), 40, 200, or 1000 ppm (w/w) for rats and 0, 125, 500, or 2000 ppm for mice. Survival rates of the high-dosed male rats and male mice were significantly decreased compared with those of the respective controls, and this was attributed to the increased number of cancer deaths. Therefore, the high-dose levels were considered not to exceed the maximum tolerated dose. Significant decreases in red blood cell counts and hematocrit value and an increase in mean corpuscular volume were noted in the p-CNB-fed rats and mice. Nonneoplastic splenic lesions were characterized by capsule hyperplasia, fibrosis, fatty metamorphosis, and increased extramedullary hematopoiesis in rats, and congestion, increased extramedullary hematopoiesis, hemosiderin deposition, and ossification in mice. Incidences of fibromas, fibrosarcomas, osteosarcomas, sarcomas (NOS), and hemangiosarcomas in males and fibrosarcomas in females were significantly increased in the spleen of high-dosed rats. The most frequently observed splenic tumor was fibrosarcomas, followed by fibromas. The tumor incidences were increased in a dose-related manner and were more prevalent in males than in females. The malignant tumors metastasized mainly to the liver, peritoneum, and pancreas. Adrena/medullary hyperplasia and pheochromocytomas were significantly increased in the p-CNB-fed females. No tumor was induced in any of the p-CNB-fed mice of either sex except hepatic hemangiosarcomas in the 2000 ppm-fed females. Causative factors of p-CNB-induced carcinogenicity and chronic toxicity are discussed in light of the subchronic and chronic hematotoxicity reported in our present and previous studies and in the literature.

Administration, Oral↗

Whole-body MR imaging for detection of bone metastases in children and young adults: comparison with skeletal scintigraphy and FDG PET.

OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy of whole-body MR imaging, skeletal scintigraphy, and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for the detection of bone metastases in children. SUBJECTS AND METHODS: Thirty-nine children and young adults who were 2--19 years old and who had Ewing's sarcoma, osteosarcoma, lymphoma, rhabdomyosarcoma, melanoma, and Langerhans' cell histiocytosis underwent whole-body spin-echo MR imaging, skeletal scintigraphy, and FDG PET for the initial staging of bone marrow metastases. The number and location of bone and bone marrow lesions diagnosed with each imaging modality were correlated with biopsy and clinical follow-up as the standard of reference. RESULTS: Twenty-one patients exhibited 51 bone metastases. Sensitivities for the detection of bone metastases were 90% for FDG PET, 82% for whole-body MR imaging, and 71% for skeletal scintigraphy; these data were significantly different (p < 0.05). False-negative lesions were different for the three imaging modalities, mainly depending on lesion location. Most false-positive lesions were diagnosed using FDG PET. CONCLUSION: Whole-body MR imaging has a higher sensitivity than skeletal scintigraphy for the detection of bone marrow metastases but a lower sensitivity than FDG PET.

Adolescent↗

Detection of simian virus 40 DNA sequence in human primary glioblastomas multiforme.

OBJECT: Deoxyribonucleic acid oncoviruses can induce neoplastic transformation of cells because their viral proteins interfere with antiproliferative cellular proteins. Simian virus 40 (SV40) is a DNA virus that induces the emergence of ependymomas, choroid plexus tumors, mesotheliomas, osteosarcomas, sarcomas, and various tumors when injected into newborn hamsters. Recently, approximately 60% of human ependymomas, choroid plexus tumors, and mesotheliomas were reported to contain and express SV40 DNA sequences. In this study the presence of SV40 DNA sequences was investigated in human brain tumors. METHODS: Three of 32 glioblastomas mutiforme (GBMs), but none of two ependymomas and five medulloblastomas, were found to possess SV40 DNA sequences when examined using polymerase chain reaction (PCR). The DNA sequence analysis of PCR-amplified fragments disclosed that the samples were identical to the regulatory region of SV40. All three GBMs, which arose in elderly patients with wild-type p53, were considered to be primary (de novo) tumors. Although each of the three tumors was immunohistochemically negative for SV40 T antigen, in situ hybridization successfully demonstrated the messenger RNA for SV40 T antigen. CONCLUSIONS: The results of this study indicate that latent infection of SV40 in elderly people may be implicated in the tumorigenesis of certain primary GBMs.

Adolescent↗

Pediatric Clinical Trials.

Clinical trials specifically tailored to the unique tumors and leukemias of children have resulted in increased survival rates approaching or exceeding 70% for most diseases. These studies have been carried out by investigators at large, independent institutions or through the auspices of the Children's Cancer Group or Pediatric Oncology Group. The National Cancer Institute has also supported pediatric disease-focused efforts for rhabdomyosarcoma, Wilms tumor, Ewing's sarcoma, osteosarcomas and other diseases. The present-day training of pediatric hematology/oncology fellows assures continuing contributions to the biology of childhood malignant lesions through applications of translational research.

Journal Article↗

Family with Li-Fraumeni syndrome and no evidence of a germline mutation of the p53 gene or chromosomal aberrations.

Li-Fraumeni syndrome is a rare autosomal, dominant trait of diverse types of cancers in children and young adults, with a predominance of soft tissue sarcomas, osteosarcomas, brain tumours, adrenocortical and breast carcinomas, as well as leukaemias. We present a family with an unusual cancer history fulfilling the criteria of Li-Fraumeni syndrome. Mutational analysis of the p53 gene in constitutional DNA of several affected members of the family did not show any germline p53 defect. Cytogenetic studies did not reveal any structural aberrations.

Journal Article↗