Intense p53 staining is a valuable prognostic indicator for poor prognosis in medulloblastoma/central nervous system primitive neuroectodermal tumors.

UNLABELLED: Intense p53 immunostaining may predict for a poor prognosis in central nervous system primitive neuroectodermal tumor of childhood. BACKGROUND: Medulloblastoma is a common childhood primary brain tumor. Potential prognostic indicators for patients with local disease are age, extent of resection, and gender. However, none of these are well established. Immunohistologic staining is a potentially useful means to identify high-risk patients. The purpose of this clinical pathologic study was to investigate the prognostic significance of GFAP, synaptophysin, Ki-67, and p53 immunostaining in medulloblastoma/central nervous system primitive neuroectodermal tumors (CNS PNETs.) MATERIALS AND METHODS: The records of 40 patients with CNS PNETs were reviewed. Their surgical specimens were immunostained for p53, glial fibrillary acidic protein (GFAP), synaptophysin, and Ki-67. The p53 specimens were scored blindly for the intensity of staining of nuclei (intense vs weak) and the quantity of cells stained. The Ki-67, GFAP, and synaptophysin specimens were analyzed for quantity of cells stained. RESULTS: Ten patients' specimens stained intensely for the p53 protein. Eleven had weakly staining nuclei. Nineteen specimens had no staining. The patients with specimens that stained intensely had a statistically significant decreased disease free survival (P = 0.03). Mere presence or quantity of p53 nuclear staining did not correlate with disease free survival. Immunohistochemical staining for Ki-67, GFAP, and synaptophysin did not correlate with disease free survival. Clinical parameters of age, gender, and extent of resection also did not approach statistical significance for disease free survival. CONCLUSION: Intense nuclear staining for p53 was the only variable in this clinical pathologic study that reached statistical significance for disease free survival. This suggests that intense staining for p53 may be the most important prognostic indicator for non-metastatic CNS PNETs. p53 Immunostaining with antibodies against p53 in CNS PNETs should be studied in a multi-institutional setting with larger numbers of patients.

The clinical application of dynamic shielding and imaging in moving table total body irradiation.

The moving table technique for total body irradiation (MTT TBI) has some advantages in regard to dose homogeneity, patient positioning and comfort. However, divergence of the radiation field coupled with patient motion necessitates corresponding motion of the shielding blocks and verification film so that penumbra is minimized. MTT TBI system is presented, together with dose calculations, incorporating moving trays for shields and film to ensure dose delivery with minimal penumbra of the blocked field.

Contamination of the pleural surfaces in childhood sarcoma. Use of colloidal P-32 to reduce radiation dose to the whole lung.

Children with pulmonary sarcomas who have diffuse contamination of the pleural cavity present a difficult management problem for the radiation oncologist. Doses required to control even microscopic disease exceed lung tolerance. We report on the use of intracavity colloid P-32 in an attempt to treat the pleural surface and spare normal lung parenchyma and tissues of the chest wall. Three children--18 months, 12 years, and 3 years of age--had spillage of pulmonary sarcomas into the chest cavity. All children were treated with systemic chemotherapy. Initially, 0.5 mCi of technetium sulfur colloid (99mTc-sulfur colloid) was instilled into the pleural space to ascertain even distribution of isotope. This was then followed by installation of 5.0 mCi of colloidal P-32. Uniform distribution was then confirmed by bremsstrahlung scanning. All three patients are in complete remission 3.5 years, 3 years, and 1 year after treatment, respectively. The major toxicity was asymptomatic pleural thickening, which could be confused with disease. This was confirmed histologically to be fibrous in the first patient. The process diminished or stabilized with time in all 3 patients over the period of observation. In this small series, intrapleural colloidal P-32 appeared to be safe and well tolerated and would be expected to be less toxic than wide-field external beam in the treatment of spilled pulmonary sarcomas.

Overexpression of heat shock protein (hsp) 70 associated with abnormal p53 expression in cancer of the pancreas.

Heat shock proteins (hsp) are involved in degradation or chaperoning nascent and abnormal proteins to various subcellular locations. p53 tumour suppressor gene overexpression and mutation occur frequently in pancreatic cancers. Mutant p53 proteins produced in cancers of other sites have been found to form complexes with hsp 70. Consequently, binding to hsp 70 may be used to indicate the presence of mutant p53 proteins. The presence of hsp 70 was investigated by immunohistochemistry in core biopsies of 42 adenocarcinomas of the pancreas (well differentiated, N = 1 and moderate to poorly differentiated, N = 41). Four cases of islet cell tumours were included in the study. These neoplasias were compared with biopsies of chronic pancreatitis (N = 9) and normal pancreas (N = 5). The majority of adenocarcinomas, 24/42 (57%), showed expression of both hsp 70 and p53. None of the islet cell tumours or cases of chronic pancreatitis showed p53 and hsp 70 coexpression. Only 1 (20%) of the normal pancreas showed concurrent nuclear immunostaining for p53 and cytoplasmic immunostaining for hsp 70. The high proportion of pancreatic adenocarcinoma showing immunoreactivity for both hsp 70 and p53 may indicate high mutation rate of the p53 gene in this tumour. Further studies using molecular techniques are required to elucidate the nature of both hsp and p53 genes in pancreatic cancers.

Distribution of type IV collagen in pancreatic adenocarcinoma and chronic pancreatitis.

Changes in the basement membrane are present in various neoplastic conditions such as neurofibrosarcoma, cervical carcinoma, colorectal cancers and hepatoblastoma. This study examines the expression of type IV collagen in the basement membrane, using an immunohistochemical method, in the normal pancreas (n = 10), chronic pancreatitis (n = 15) and pancreatic adenocarcinoma (n = 30). The formalin fixed, paraffin embedded tissue was sectioned and pretreated with protease prior to immunostaining for type IV collagen. There was a statistically significant difference in type IV collagen expression between pancreatic carcinoma and chronic pancreatitis (P = 0.0001; chi 2 test with continuity correction). In pancreatic adenocarcinoma, type IV collagen distribution in the basement membrane was discontinuous and irregular or absent around individual or groups of neoplastic cells (n = 30). Most cases of chronic pancreatitis showed continuous pattern of basement membrane type IV collagen around residual ducts (n = 10). In the normal pancreas, only one of the ten cases showed discontinuous basement membrane around pancreatic ducts, while in the rest of the cases, the pattern was continuous. This study suggests that there is abnormal distribution of type IV collagen in the basement membrane in pancreatic carcinoma, which may be related to either abnormal deposition or degradation of the collagen. Immunostaining for type IV collagen may be of some diagnostic use for distinguishing pancreatic adenocarcinoma from problematic cases of chronic pancreatitis.

The reirradiation of recurrent bronchogenic carcinoma with external beam irradiation.

Symptomatic local failure following thoracic irradiation for bronchogenic carcinoma presents a clinical challenge to the Radiation Oncologist. We retrospectively evaluated the efficiency of reirradiation with external beam radiation of 30 patients. The median dose of initial irradiation was 6,000 cGy in 6 weeks. The median time following initial irradiation to recurrence was 12 months. The median dose of retreatment was 3,030 cGy in 3 weeks. Of the symptomatic patients, 88% and 70% subjectively responded to initial irradiation and to reirradiation, respectively. Retreatment toxicity included radiation esophagitis (6 patients), dry desquamation (4 patients), and symptomatic radiation pneumonitis (1 patient). Based on this study, doses of external beam radiation in the range of 2,000-3,000 cGy in 2 to 3 weeks appear safe and effective in reirradiating recurrent bronchogenic carcinoma.

Clinical presentation, treatment, and outcome of trilateral retinoblastoma.

In this report, three new cases of trilateral retinoblastoma are presented. The clinical presentation, treatment, and outcome of the patients are described and compared with those of 32 cases that have been previously reported in the literature. A positive family history was obtained in 68% of the patients. The mean age at diagnosis of bilateral retinoblastoma was 7.2 months. The mean age at diagnosis of trilateral disease was 39.7 months, resulting in a mean latent interval of 32.6 months. The mean time from diagnosis of trilateral retinoblastoma to death was 6.6 months, and all patients died with spinal metastases. The patients who received no therapy survived an average of 1.3 months after the diagnosis of trilateral disease. The patients who received any form of definitive therapy survived 9.7 months. Five patients who had complete or dramatic response to therapy by computed tomography scans had local intracranial tumor present at autopsy. Therefore, more aggressive local therapy may be warranted.

Skin cancer in patients with chronic radiation dermatitis.

The cases of 76 patients with chronic radiation dermatitis resulting from low-dose ionizing radiation for benign disease were reviewed retrospectively for risk factors leading to the development of neoplasia. The patients were studied with respect to original hair color, eye color, sun reactive skin type, benign disease treated, area treated, age at treatment, and age at development of first skin cancer. Analysis of data showed 37% of patients had sun-reactive skin type I, 27% had type II, and 36% had type III. Types IV through VI were not represented. There appeared to be an overrepresentation of types I and II. Increased melanin pigmentation may therefore be either directly or indirectly protective against the development of skin cancers in patients who have received low-dose superficial ionizing radiation for benign disease. The sun-reactive skin type of patients with chronic radiation dermatitis may be used as a predictor of skin cancer risk when the total dose of ionizing radiation is not known.

The palliation of osseous metastasis with 32P or 89Sr compared with external beam and hemibody irradiation: a historical perspective.

Radiation is an effective modality for palliation of osseous metastases. In patients with a limited number of lesions, local external beam irradiation is the most expedient method of delivering radiation therapy. Complete or partial relief of pain will occur in 80-90% of patients. When metastases are widespread or when new sites continue to appear, localized external irradiation becomes logistically difficult. In such cases, hemibody irradiation has been effective with an overall response rate of 85%. However, nausea, vomiting, diarrhea, and bone marrow and pulmonary toxicity may complicate therapy. In these cases, an effective alternative is systemic phosphorus-32 (32P) or strontium-89 (89Sr). Relief of pain in the range of 60-90% has been reported. Toxicity of 32P is largely that of bone marrow suppression, while 89Sr appears to be relatively marrow-sparing. In this review, we consider systemic 32P or 89Sr as viable options to external beam or hemibody irradiation in the presence of numerous bone metastases.

A comparison of lung metastases and natural killer cell activity in daily fractions and weekly fractions of radiation therapy on murine B16a melanoma.

C57BL/6J male mice were inoculated with 5 X 10(5) B16a melanoma cells. Seven days post-inoculation, when the tumor had grown to 8.0-10.0 mm in diameter, 120 tumor-bearing mice were randomly divided into three groups: (1) sham-irradiated controls, (2) mice receiving 200 cGy five times a week for 6 weeks, and (3) mice receiving 800 cGy once a week for 4 weeks. Thirty mice in each group were sacrificed 47 days postinoculation. Ten mice in each group were observed for the survival time data. The primary tumor was significantly smaller and the number of lung metastases were significantly fewer in mice treated with 800 cGy once a week compared to mice treated with 200 cGy five times a week. When natural killer (NK) cell activity was assessed against YAC-1 tumor targets, it was found to be significantly higher in mice treated with a single large weekly dose of irradiation. These results show that B16a melanoma responds more favorably to a single large dose of irradiation administered once a week compared to the smaller conventional fraction administered five times a week. This beneficial effect correlates with an increase in NK activity, indicating that there may be a causal relationship.

Gliomas in children following radiation therapy for lymphoblastic leukemia.

Four children treated for acute lymphoblastic leukemia developed intracranial gliomas between 40 and 120 months following multiagent chemotherapy, prophylactic whole brain irradiation, and intrathecal Methotrexate. The diagnosis of glioma was confirmed in each case with biopsy or autopsy. These children were part of a larger series of 73 patients with acute lymphoblastic leukemia treated at Indiana University receiving 24 Gy as per the protocol guidelines of the Children's Cancer Study Group. Currently 42 patients of the original 73 children survive in continuous remission.

Sensitivity of radionuclide brain scan and computed tomography in early detection of viral meningoencephalitis.

The sensitivity of radionuclide imaging and computed tomography (CT) was evaluated in 25 patients for early detection of viral meningoencephalitis. Diagnosis was based on clinical evidence, cerebrospinal fluid (CSF) studies, electroencephalography (EEG) and radionuclide imaging. Computed tomography with contrast enhancement was performed within four days after onset of neurological signs or symptoms in 23 patients; no significant findings such as low-absorption abnormalities, mass effect or abnormal enhancement were seen. Radionuclide imaging demonstrated a sensitivity of 90% in the detection of viral meningoencephalitis; the temporal lobe was most commonly involved in patients with herpes encephalitis. Radionuclide imaging should be considered as the first diagnostic procedure in suspected early viral meningoencephalitis.