Loss of p53 promotes anaplasia and local invasion in ret/PTC1-induced thyroid carcinomas.
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Papillary thyroid carcinomas in humans are associated with the ret/PTC oncogene and, following loss of p53 function, may progress to anaplastic carcinomas. Mice with thyroid-targeted expression of ret/PTC1 developed papillary thyroid carcinomas that were minimally invasive and did not metastasize. These mice were crossed with p53-/- mice to investigate whether loss of p53 would promote anaplasia and metastasis of ret/PTC1-induced thyroid tumors. The majority of p53-/- mice died or were euthanized by 17 weeks of age due to the development of thymic lymphomas, soft tissue sarcomas, and testicular teratomas. All ret/PTC1 mice developed thyroid carcinomas, but tumors in p53-/- mice were more anaplastic, larger in diameter, more invasive, and had a higher mitotic index than tumors in p53+/+ and p53+/- mice. Thyroid tumors did not metastasize in any of the experimental p53+/+ and p53+/- mice +info)
Association of expression of CD44v6 with systemic anaplastic large cell lymphoma: comparison with primary cutaneous anaplastic large cell lymphoma.
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CD44 is a ubiquitous multifunctional cell surface adhesion molecule family. High expression of the standard form, CD44s (CD44), and its variant form, CD44v6, has been reported to be associated with tumor dissemination in non-Hodgkin lymphoma. To evaluate the potential role of CD44 and/or CD44v6 in different entities of anaplastic large cell lymphoma (ALCL), 30 cases of systemic ALCL (sALCL; 20 cases) and primary cutaneous ALCL (cALCL; 10 cases) were compared for expression of CD44 and CD44v6 by immunohistochemical staining. Expression of CD44v6 also was analyzed with respect to expression of anaplastic lymphoma kinase (ALK) in sALCL. No difference of CD44 expression was noted between sALCL and cALCL In contrast, expression of CD44v6 was found in 18 (90%) of sALCL cases and in 5 (50%) of cALCL cases. There was no correlation between expression of CD44v6 and expression of ALK in sALCL. These results indicate that expression of CD44v6 rather than CD44 correlates with sALCL. Furthermore, these results suggest that CD44v6 and ALK may be independent predictors of risk for the systemic phenotype of ALCL. (+info)
Malignant peritoneal mesothelioma deciduoid or anaplastic variant? Point to ponder.
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A case of peritoneal mesothelioma displaying unusual morphology, occurring in a 53 year old woman is described. The role of immunohistochemistry and electron microscopy in the evaluation of this tumor is stressed. The appropriate terminology to be used and possible etiologic factor are also discussed. (+info)
Clinical and biologic significance of nuclear unrest in Wilms tumor.
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BACKGROUND: Nuclear unrest is a term applied to Wilms tumors (WT) with favorable histology that show nuclear enlargement similar to that seen in anaplasia but with no abnormal mitotic figures. This study was undertaken to evaluate the clinical and pathogenetic significance of WT with nuclear unrest. METHODS: The authors reviewed primary nephrectomy specimens and clinical data from 173 patients who were treated for WT on 1 of 5 consecutive clinical trials at St. Jude Children's Research Hospital. A subset of 70 patients was selected for p53 immunohistochemistry. Seventeen samples of recurrent tumors were also reviewed. RESULTS: WT with nuclear unrest had age and stage distribution similar to that for WT with favorable histology. Patients who had tumors with favorable histology, nuclear unrest, and anaplastic histology had 5-year cumulative incidences of recurrence of 12.2%, 22.2%, and 36.4%, respectively (P = 0.010). Despite the difference in recurrence incidence, patients who had tumors with nuclear unrest and patients who had tumors with favorable histology had nearly identical overall survival. Immunostaining for p53 was positive in 2 of 24 tumors (8.3%) with favorable histology, 1 of 25 tumors (4%) with nuclear unrest, and 16 of 21 tumors (76%) with anaplastic histology (P < 0.001). Histologic review of samples from recurrent tumors showed that 7 of 10 of primary tumors converted from favorable histology to either nuclear unrest or anaplastic histology in the recurrent tumor. CONCLUSIONS: WT with nuclear unrest more closely resembles favorable histology than anaplastic histology, both clinically and pathogenetically. Analysis of samples from recurrent tumors suggests that WT with nuclear unrest represents an intermediary in the continuum from favorable histology to anaplastic histology. For treatment stratification, it is appropriate to continue grouping nuclear unrest with favorable histology, although a larger analysis will be necessary to confirm the current findings. (+info)
Gangliogliomas: A report of five cases.
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Gangliogliomas are rare tumors of the Central Nervous System. Five gangliogliomas were diagnosed out of 1560 brain tumours surgically resected out in a period of 5 years accounting for 0. 32%. We have tried to discuss in detail the pathological features of these tumours and have mentioned the clinical and radiological features associated with them. All the slides, tissue blocks and pathology reports of the surgical specimens of gangliglioma were reviewed and the clinical and radiological data reviewed. The ages of the patients ranged from 7-65 years with 4 males and 1 female. The tumors were located in the lateral ventricle (a rare site), temporal, parietal and the frontal lobes with duration of seizures varying from 1-9 years. The tumors were diagnosed by the presence of a dual population of neoplastic ganglionic and glial components. The glial components consisted of pilocytic astrocytes (l case), fibrillary astrocytes (2 cases), oligodendrocytes (1 case) and anaplastic astrocytes and oligodendrocytes (1 case). There was one-grade I GG, three-Grade II GGs and one-grade III GG. Astrocytes were the commonest glial component of GGs, either pilocytic or fibrillary. Oligodendrocytes as the glial component of GGs was seen in 2 cases one of which was anaplastic and this is a rare finding. (+info)
Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus.
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BACKGROUND: p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. METHODS: p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. RESULTS: p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. CONCLUSION: Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein. (+info)
Multiple metastases to the small bowel from large cell bronchial carcinomas.
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AIM: Metastases from lung cancer to gastrointestinal tract are not rare at postmortem studies but the development of clinically significant symptoms from the gastrointestinal metastases is very unusual. METHODS: Formalin-fixed, paraffin-embedded tissues were cut into 5 microm thick sections and routinely stained with hematoxylin and eosin. Some slides were also stained with Alcian-PAS. Antibodies used were primary antibodies to pancytokeratin, cytokeratin 7, cytokeratin 20, epithelial membrane antigen, vimentin, smooth muscle actin and CD-117. RESULTS: We observed three patients who presented with multiple metastases from large cell bronchial carcinoma to small intestine. Two of them had abdominal symptoms (sudden onset of abdominal pain, constipation and vomiting) and in one case the tumor was incidentally found during autopsy. Microscopically, all tumors showed a same histological pattern and consisted almost exclusively of strands and sheets of poorly cohesive, polymorphic giant cells with scanty, delicate stromas. Few smaller polygonal anaplastic cells dispersed between polymorphic giant cells, were also observed. Immunohistochemistry showed positive staining of the tumor cells with cytokeratin and vimentin. Microscopically and immunohistochemically all metastases had a similar pattern to primary anaplastic carcinoma of the small intestine. CONCLUSION: In patients with small intestine tumors showing anaplastic features, especially with multiple tumors, metastases from large cell bronchial carcinoma should be first excluded, because it seems that they are more common than expected. (+info)
Salvage chemotherapy with cyclophosphamide for recurrent temozolomide-refractory anaplastic astrocytoma.
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BACKGROUND: A prospective Phase II study of cyclophosphamide (CYC) was conducted in adult patients with recurrent temozolomide-refractory anaplastic astrocytoma (AA) with a primary objective of evaluating 6-month progression-free survival (PFS). METHODS: Forty patients (28 men, 12 women) ages 26-57 years (median, 43 yrs) with neuroradiographically recurrent AA were treated. All patients had previously been treated with surgery and involved-field radiotherapy. Additionally, all patients were treated with temozolomide (TMZ) chemotherapy after radiotherapy. All patients were treated at recurrence with CYC administered intravenously on 2 consecutive days (750 mg/m2/day) every 4 weeks (operationally defined as a single cycle). Neurologic and neuroradiographic evaluation were performed every 8 weeks. RESULTS: All patients were evaluable. A total of 215 cycles of CYC (median, 4 cycles; range 2-12 cycles) was administered. CYC-related toxicity included alopecia (all patients, 100%), anemia (5, 12.5%), thrombocytopenia (6, 15%), and neutropenia (8, 20%). Four (10%) patients required transfusion. Nine patients (22.5%) (95% confidence interval [95% CI], 11%-39%) demonstrated a neuroradiographic partial response, 16 patients (40.0%) (95% CI, 25%-57%) demonstrated stable disease, and 15 patients (37.5%) (95% CI, 23%-54%) had progressive disease after 2 cycles of CYC. Time to tumor progression ranged from 2-19 months (median, 4 mos; 95% CI, 2-6 mos). Survival ranged from 2-26 months (median, 8 mos; 95% CI, 6-10 mos). The 6-month and 12-month PFS was 30% and 8%, respectively. CONCLUSIONS: CYC demonstrated modest efficacy with acceptable toxicity in this cohort of adult patients with recurrent anaplastic astrocytoma, all of whom had failed prior TMZ chemotherapy. (+info)