Centrally Reduced Diffusion Sign for Differentiation between Treatment-Related Lesions and Glioma Progression: A Validation Study.

BACKGROUND AND PURPOSE: Differentiating between treatment-related lesions and tumor progression remains one of the greatest dilemmas in neuro-oncology. Diffusion MR imaging characteristics may provide useful information to help make this distinction. The aim of the study was to assess the diagnostic accuracy of the centrally reduced diffusion sign for differentiation of treatment-related lesions and true tumor progression in patients with suspected glioma recurrence. MATERIALS AND METHODS: The images of 231 patients who underwent an operation for suspected glioma recurrence were reviewed. Patients with susceptibility artifacts or without central necrosis were excluded. The final diagnosis was established according to histopathology reports. Two neuroradiologists classified the diffusion patterns on preoperative MR imaging as the following: 1) reduced diffusion in the solid component only, 2) reduced diffusion mainly in the solid component, 3) no reduced diffusion, 4) reduced diffusion mainly in the central necrosis, and 5) reduced diffusion in the central necrosis only. Diagnostic accuracy metrics and the area under the receiver operating characteristic curve were estimated for the diffusion patterns. RESULTS: One hundred three patients were included (22 with treatment-related lesions and 81 with tumor progression). The diagnostic accuracy results for the centrally reduced diffusion pattern as a predictor of treatment-related lesions ("mainly central" and "exclusively central" patterns versus all other patterns) were as follows: 64% sensitivity (95% CI, 41%-83%), 84% specificity (95% CI, 74%-91%), 52% positive predictive value (95% CI, 37%-66%), and 89% negative predictive value (95% CI, 83%-94%). CONCLUSIONS: The centrally reduced diffusion sign is associated with the presence of treatment effect. The probability of a histologic diagnosis of a treatment-related lesion is low (11%) in the absence of centrally reduced diffusion.

Differentiation of brain tumor-related edema based on 3D T1rho imaging.

BACKGROUND AND PURPOSE: Cerebral edema associated with brain tumors is an important source of morbidity. Its type depends largely on the capillary ultra-structures of the histopathologic subtype of underlying brain tumor. The purpose of our study was to differentiate vasogenic edema associated with brain metastases and infiltrative edema related to diffuse gliomas using quantitative 3D T1 rho (T1ρ) imaging. MATERIALS AND METHODS: Preoperative MR examination including whole brain 3D T1ρ imaging was performed in 23 patients with newly diagnosed brain tumors (9 with metastasis, 8 with lower grade glioma, LGG, 6 with glioblastoma, GBM). Mean T1ρ values were measured in regions of peritumoral non-enhancing T2 signal hyperintensity, excluding both enhancing and necrotic or cystic component, and normal-appearing white matter. RESULTS: Mean T1ρ values were significantly elevated in the vasogenic edema surrounding intracranial metastases when compared to the infiltrative edema associated with either LGG or GBM (p=0.02 and <0.01, respectively). No significant difference was noted between T1ρ values of infiltrative edema between LGG and GBM (p=0.84 and 0.96, respectively). CONCLUSION: Our study demonstrates the feasibility and potential diagnostic role of T1ρ in the quantitative differentiation between edema related to intracranial metastases and gliomas and as a potentially complementary tool to standard MR techniques in further characterizing pathophysiology of vasogenic and infiltrative edema.

Perfusion MR imaging of an intracranial collision tumor confirmed by image-guided biopsy.

We present a patient with a new intracranial mass lesion that was initially interpreted as a metastasis on conventional anatomic MR imaging. On dynamic, contrast-enhanced, susceptibility-weighted perfusion MR imaging, however, there were regional hemodynamic differences within the lesion. Image-guided open biopsy targeting these regions uncovered a collision tumor between a typical meningioma and a metastatic breast carcinoma. In cases where conventional anatomic MR imaging is ambiguous, physiology-based neuroimaging methods provide complementary physiologic information useful for discriminating between histologically unique tissue types.

Comparison of microvascular permeability measurements, K(trans), determined with conventional steady-state T1-weighted and first-pass T2*-weighted MR imaging methods in gliomas and meningiomas.

BACKGROUND AND PURPOSE: The widely accepted MR method for quantitating brain tumor microvascular permeability, K(trans), is the steady-state T1-weighted gradient-echo method (ssT1). Recently the first-pass T2*-weighted (fpT2*) method has been used to derive both relative cerebral blood volume (rCBV) and K(trans). We hypothesized that K(trans) derived from the ssT1 and the fpT2* methods will correlate differently in gliomas and meningiomas because of the unique differences in morphologic and functional status of each tumor vascular network. METHODS: Before surgery, 27 patients with newly diagnosed gliomas (WHO grade I-IV; n = 20) or meningiomas (n = 7) underwent conventional anatomic MR imaging and 12 dynamic ssT1 acquisitions followed by 60 dynamic fpT2* images before and after gadopentate dimeglumine administration. The 3 hemodynamic variables-fpT2* rCBV, fpT2* K(trans), and ssT1 K(trans)-were calculated in anatomically identical locations and correlated with glioma grade. The fpT2* K(trans) values were compared with ssT1 K(trans) for gliomas and meningiomas. RESULTS: All 3 hemodynamic variables displayed distinct distributions among grades 2, 3, and 4 gliomas by using the Kruskal-Wallis test. Only K(trans) values, and not rCBV, could differentiate between grade 4 and lower-grade gliomas by using the Wilcoxon rank sum test. The fpT2* K(trans) was highly predictive of ssT1 K(trans) for gliomas, with an estimated regression coefficient of 0.49 (P < .001). For meningiomas, however, fpT2* K(trans) values correlated poorly with ssT1 K(trans) values (r = 0.26; P = .74). CONCLUSION: Compared with rCBV, K(trans) values derived from either ssT1 or fpT2* were more predictive of glioma grade. The fpT2* K(trans) was highly correlated with ssT1 K(trans) in gliomas but not in meningiomas.

Classification of small cell lung cancer and pulmonary carcinoid by gene expression profiles.

Small cell lung cancer is a common type of lung cancer that is generally classified within the spectrum of neuroendocrine lung neoplasms. Using high-density cDNA arrays, we profiled gene expression of small cell lung cancers and compared these expression profiles to those of normal bronchial epithelial cells and pulmonary carcinoids, which are classified as benign neuroendocrine tumors. We found the overall expression profiles of two small cell lung cancer cell lines, two microdissected tissue samples of primary small cell lung cancer, and cultured bronchial epithelial cells to be relatively similar to one another, with an average Pearson correlation coefficient for these comparisons of 0.63. However, we found the expression profiles of small cell lung cancers (and bronchial epithelial cells) to be surprisingly dissimilar to those of two samples of pulmonary carcinoid tumors, with an average correlation coefficient for these comparisons of 0.20. We then compared the pulmonary carcinoid expression profiles to those of two samples of infiltrating astrocytic brain cancers (oligodendroglioma and high-grade astrocytoma) and found similarity of gene expression among these four samples (average correlation coefficient, 0.57). These gene expression profiles suggest that small cell lung cancers are closely related to (and possibly derived from) epithelial cells, and that pulmonary carcinoids are related to neural crest-derived brain tumors. More generally, our results suggest that broad profiles of gene expression may reveal similarities and differences between tumors that are not apparent by traditional morphological criteria.

Concordant changes of pyrimidine metabolism in blasts of two cases of acute myeloid leukemia after repeated treatment with ara-C in vivo.

Though data from cell lines are abundant, the reason for the development of resistance to 1-beta-D arabinofuranosylcytosine (ara-C) in vivo remains unresolved. A broad interpatient variation of metabolic parameters has further complicated interpretation of the results. The present study compares ara-C metabolism in leukemic blasts of two patients with newly diagnosed disease, before and after repeated treatment with ara-C containing chemotherapy regimens in vivo. Membrane transport of ara-C was unchanged after treatment. In addition, cell-free extracts of blasts obtained after treatment failure showed an unchanged cytidine deaminase activity. Though deoxycytidine kinase activity in cell extracts was unaltered or increased after treatment failure, the activity in situ, measured as the rate of 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP) formation, was decreased. This could be shown to be due to an expansion of the deoxycytidine triphosphate (dCTP) pool. The severalfold increase in dCTP pool was accompanied by a decrease in thymidine triphosphate (dTTP) pool and correlated with a decrease in deoxycytidylate deaminase (dCMP-deaminase) activity in cell free extracts. Low dCMP-deaminase activity had been shown to confer an ara-C resistant phenotype to cell lines in vitro. Data presented in this paper show that a selection for leukemic blasts with low dCMP-deaminase activity can also be favored by ara-C containing treatment regimens in vivo. Our data suggest that this mechanism might contribute to treatment failure.

Nuclear localization and mutation of beta-catenin in medulloblastomas.

The adenomatous polyposis coli (APC) gene, a member of the Wingless/Wnt signal transduction pathway, has been implicated in the development of medulloblastomas in Turcot's syndrome. beta-catenin also functions in this highly conserved signaling pathway and is instrumental in growth and development. Mutations in either APC or beta-catenin can stabilize beta-catenin protein. Stabilized beta-catenin complexes with Tcf/Lef transcription factors and moves from the cytoplasm into the nucleus where it regulates the transcription of c-Myc and other genes. Nuclear localization of beta-catenin therefore implies activation of the signaling pathway. We have analyzed the subcellular localization of beta-catenin in 51 sporadic medulloblastomas and in 1 medulloblastoma arising in a patient with Turcot's syndrome. Nuclear beta-catenin staining was present in 9 of the sporadic tumors (18%) and in the 1 medulloblastoma from a Turcot's patient. The remaining 41 cases did not show nuclear staining. This confirms earlier observations that Wingless/Wnt signaling is involved in a subset of sporadic medulloblastomas. We also examined 48 glial and meningeal CNS tumors, all of which were negative for nuclear beta-catenin. Exon 3 of beta-catenin was sequenced in 6 of the 9 sporadic medulloblastomas with nuclear beta-catenin staining. Five of the 6 tumors sequenced had mutations affecting highly conserved beta-catenin phosphorylation sites involved in protein stability. These data suggest a simple immunohistochemical method to screen for beta-catenin mutations in medulloblastomas.

Apoptosis, neuronal maturation, and neurotrophin expression within medulloblastoma nodules.

Nodular/desmoplastic medulloblastomas are a well-established histopathological subtype containing reticulin-free nodules or "pale islands' that are comprised of cells with round "neurocytic" nuclei and abundant cytoplasm. Significant neuronal maturation occurs within nodules. We used immunohistochemistry to evaluate neuronal differentiation in the nodules of 6 of these tumors. The neuronal markers NeuN, synaptophysin, and MAP-2 were identified in the "pale islands" of all 6 nodular medulloblastomas examined, and high and medium molecular weight nonphosphorylated neurofilaments were detected in 2 of the 6 cases. We also observed collections of apoptotic cells within nodules. Given the known role of neurotrophin signaling in neuronal maturation and apoptosis, we analyzed immunohistochemically the distribution of neurotrophin receptors TrkA and TrkC and their primary ligands NGF and NT3 in 14 nodular medulloblastomas. TrkA and TrkC were detected in 13 and 10 cases, respectively, and were predominantly localized within nodules. NGF and NT3 were distributed diffusely with some nodular accentuation. The localized expression of Trk receptors within nodules of desmoplastic medulloblastomas suggests neurotrophin signaling is involved in the apoptosis and neuronal differentiation in medulloblastomas. We also examined expression of p53 and BCL-2 in these tumors; both were prominent in internodular regions but only weakly expressed within nodules. Trk receptors, p53, and BCL-2 are all expressed during development of the normal cerebellum. Interestingly, the immunohistochemical expression profile of these proteins in the differentiating nodules of medulloblastomas is in many ways similar to their expression in the developing cerebellum. Thus similar signaling pathways may be operational in cerebellar development and medulloblastoma tumor differentiation.

Pediatric astrocytomas with monomorphous pilomyxoid features and a less favorable outcome.

Among tumors classified as pilocytic astrocytoma (PA) in the Johns Hopkins Hospital Department of Pathology files, we identified 18 cases with a distinctive monomorphous pilomyxoid histological pattern and a higher recurrence rate than that of PA with classical histological features (classical PA). The majority of the tumors occurred in infants and young children and involved the hypothalamic/chiasmatic region. The tumors were histologically similar to PA, but they were more monomorphous and more myxoid. Rosenthal fibers were not seen and only 1 of 18 tumors had eosinophilic granular bodies. At the end of the follow-up period, 6 patients were dead and 12 were alive with evidence of disease. Progression free survival (PFS) at 1 year was 38.7%. In comparison, we identified a control group of 13 classical PAs in the same age range and location as the study group. In this group, PFS at 1 year was 69.2%, which was significantly better than that for pilomyxoid tumors (p = 0.04). There was no CSF dissemination or death due to tumor progression among patients with classical PA. Eight of these patients are alive with recurrent disease, and 4 have no evidence of disease. While the monomorphous pilomyxoid tumors have some resemblance to classical PA, our results suggest that the former is a more aggressive variant or a separate entity that needs to be recognized for prognostic purposes.

Atypical teratoid/rhabdoid tumor of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma: a Pediatric Oncology Group study.

Fifty-five patients with atypical teratoid/rhabdoid tumors of the central nervous system were studied to define the clinical and pathologic features of this newly described neoplasm. The lesion occurred primarily in children younger than 2 (mean age at diagnosis, 17 months). The neoplasms were located in the posterior fossa (36 patients) and the supratentorial compartment (17 patients) or were multifocal in both compartments (2 patients) at presentation. Histologically, the tumors were composed of small cells and large, pale cells in a jumbled architectural arrangement. The small cell component resembled medulloblastoma and occasionally had cords of cells in a mucinous background, simulating chordoma. The cytoplasm of the larger cells was conspicuous with a somewhat "rhabdoid" appearance, although rhabdoid features were not always prominent. Epithelioid features in the form of poorly formed glands or Flexner-Wintersteiner rosettes were noted in a minority of lesions. The neoplasms showed striking polyphenotypic immunoreactivity, including that for vimentin, glial fibrillary acidic protein, epithelial membrane antigen, cytokeratins, synaptophysin, chromogranin, and smooth muscle actin. Using a probe for chromosome 22, seven of eight scorable cases showed a solitary signal by fluorescence in situ hybridization (FISH) consistent with monosomy 22. The eighth scorable case showed three signals by fluorescence in situ hybridization and had a translocation involving chromosome 22 reported by conventional cytogenetics. In contrast to patients with medulloblastoma, the neoplasm with which these lesions are often confused, the outcome of the patients was uniformly poor. The mean postoperative survival of patients with atypical teratoid/rhabdoid tumors was only 11 months. Local recurrence, seeding of the cerebrospinal fluid pathways, or both, were common terminal events. This study underscores the distinctive clinical, histopathologic, immunohistochemical, and cytogenetic character of this unusually aggressive tumor.

Clear cell papillary carcinoma of the liver: an unusual variant of peripheral cholangiocarcinoma.

Cholangiocarcinomas may be extrahepatic or intrahepatic; the latter are further divided into hilar and peripheral types. Peripheral cholangiocarcinomas often resemble adenocarcinomas arising in other organs. Although clear cell changes may occur in hepatocellular carcinoma and extrahepatic cholangiocarcinoma, peripheral cholangiocarcinomas with clear cell change are rare. In such cases, an extrahepatic primary carcinoma must be excluded. We present a patient with a large, clear cell papillary carcinoma in the liver. Extensive workup of the patient for other possible primary sites including kidneys, adrenals, thyroid, prostate, or urinary bladder failed to indicate any other neoplasm. The patient is alive without evidence of disease 30 months after complete resection. The histological, immunohistochemical, and electron microscopic results were most consistent with a neoplasm in the cholangiocarcinoma family. To the best of our knowledge, a clear cell papillary peripheral cholangio carcinoma has not been described previously. This neoplasm may be related to the recently described clear cell carcinomas of the gallbladder and extrahepatic bile ducts.

Effect of ribonucleotide reductase inhibitors on the growth of human colon carcinoma HT-29 cells in culture.

The effects of ribonucleotide reductase inhibitors on the growth of the human colon carcinoma cell line HT-29 were examined. Inhibitors were chosen for these studies that were specifically directed at each of the subunits of ribonucleotide reductase. The concentrations of drugs required to inhibit the growth of HT-29 cells by 50% (IC50) for hydroxyurea, 2,3-dihydro-lH-pyrazole-[2,3a]imidazole (IMPY), and 4-methyl-5-amino-l-formyl-isoquinoline thiosemicarbazone (MAIQ) were 206, 996, and 3.2 microM, respectively. Although the IC50 for deoxyadenosine alone was greater than 2,000 microM, in the presence of 5 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), which protects deoxyadenosine from deamination by adenosine deaminase, it was reduced to 112 microM. The IC50 for deoxyguanosine was 1,060 microM. The addition of 8-aminoguanosine to protect deoxyguanosine from phosphorolysis by purine nucleoside phosphorylase did not increase the toxicity of deoxyguanosine in HT-29 cells. The combination of MAIQ or IMPY and deoxyadenosine/EHNA gave strong synergistic inhibition of HT-29 cell growth. The results of these studies indicate that ribonucleotide reductase inhibitors effectively block the growth of human colon carcinoma HT-29 cells and that combinations of inhibitors directed at the individual subunits of reductase result in synergistic inhibition of HT-29 cell growth in culture.

Studies on the mechanisms of inhibition of L1210 cell growth by 3,4-dihydroxybenzohydroxamic acid and 3,4-dihydroxybenzamidoxime.

Didox and Amidox inhibit L1210 cell growth in culture. At least one of the mechanisms in the mode(s) of action of the compounds is directed at the ribonucleotide reductase site. Partially purified preparations of ribonucleotide reductase activity are inhibited by Amidox and Didox. The formation of deoxycytidine nucleotides from [14C]cytidine in intact L1210 cells is also blocked. Didox and Amidox cause the decrease in the intracellular pools of the four dNTPs. Hydroxyurea-resistant L1210 cells are not cross-resistant to either Didox or Amidox. These data suggest that Didox and Amidox are not inhibiting ribonucleotide reductase through a mechanism similar to hydroxyurea.

Esophagogastric adenocarcinoma in an E1A/E1B transgenic model involves p53 disruption.

We studied tumorigenesis and p53 immunostaining in a murine transgenic model introducing E1A/E1B under the control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR) promoter in which adenocarcinoma occurs at the squamocolumnar junction in the foregut, predominantly in males, and at no other site. Mutations of p53 are frequent in human esophageal adenocarcinoma and the E1B gene product interferes with p53-mediated apoptosis, inhibiting tumor suppression at the G(1)/S checkpoint. Transgenic animals were generated utilizing a purified linear 6.7 kb fragment of plasmid DNA containing MMTV-LTR/E1A/E1B and were confirmed by dot blot hybridization of tail DNA to (32)P-labeled E1A/E1B probe and polymerase chain reaction (PCR) amplification of E1A. Transgenic and control animals were observed for morbidity and weight changes. Eleven of 45 animals were transgenic (24% efficiency) with an estimated 5 to 57 copies of the gene per genome. Profound weight loss (>20%) led to sacrifice or death of one of five females (at 12 weeks) and four of six males (at 16 to 17 weeks). Grossly visible tumors (2 to 10 mm) were noted in the forestomach at the visible margin between the proximal (squamous-lined) stomach and the distal glandular stomach. Histologic sections confirmed adenocarcinoma arising in each case at the squamocolumnar junction with glandular formation, pleomorphism, and frequent mitotic figures. Immunostaining was positive for p53 indicating accumulation of mutated or altered p53 protein. E1A/E1B transgenic animals developed macroscopic and microscopic adenocarcinoma at the squamocolumnar junction, which corresponds to adenocarcinoma at the human esophagogastric junction. Disruption of p53 was present in the transgenic model as in the human cancer.

Well-differentiated papillary adenocarcinoma arising in a supratentorial enterogenous cyst: case report.

OBJECTIVE AND IMPORTANCE: We report a case of a well-differentiated papillary adenocarcinoma arising in an supratentorial enterogenous cyst. The clinicopathological features of this case and a brief review of the literature are presented. CLINICAL PRESENTATION: A 45-year-old woman presented with abrupt onset of sensory seizures and abnormal sensation on the left side of her face, left leg, and left arm. Radiological studies showed a cystic extraaxial tumor with mass effect in the right parietal area. The initial clinical impression was a metastatic lesion, and a comprehensive metastatic workup revealed no evidence of tumor elsewhere. INTERVENTION: A gross total resection of the solid cystic tumor was achieved by a frontoparietal craniotomy. Sixteen months after the initial surgery, the patient presented with signs of increased intracranial pressure and a large parietal cyst. The cyst was fenestrated at the time of the second craniotomy. CONCLUSION: A pathological study of the initial surgical material revealed it to be a well-differentiated papillary adenocarcinoma in association with an enterogenous cyst. The second surgical specimen consisted only of the benign cyst wall. The patient recovered uneventfully from the second surgery and was free of symptoms 6 months postoperatively. The importance of recognizing the rare possibility of malignant progression of a benign enterogenous cyst in the central nervous system is discussed.

Evidence of androgen receptor expression in squamous and adenocarcinoma of the esophagus.

Androgen receptors (AR) are known to stimulate cellular proliferation in certain tumors. We have assessed the androgen receptor status of esophageal carcinoma in surgically resected specimens as well as in established human esophageal carcinoma cells lines. In these initial studies we sought to characterize the frequency of expression of androgen receptors in squamous versus adenocarcinoma and in male versus female patients, and to assess the possible influence of AR expression on survivaL We analyzed androgen receptor expression utilizing immunohistochemistry in adenocarcinoma and squamous cell carcinoma of the esophagus in surgical specimens from 25 patients treated at Johns Hopkins Bayview Medical Center. Tumors in 7 of 21 males (33%) and 1 of 4 females (25%) showed positive androgen receptor staining with the monoclonal body antibody AR 441. There was no suggestion of a difference in expression of AR between males and females. Five of 11 adenocarcinomas (45%) and 3 of 14 squamous carcinomas were positive. Survival was similar in AR+ and AR- patients. Studies with established tissue culture cell lines showed AR expression by RT-PCR, with stronger expression of AR in adenocarcinoma lines than in squamous carcinoma lines. The presence of AR in human esophageal cancer is an impetus for further studies to assess anti-androgen therapy for treatment and or prevention of these tumors.

Giant-cell granulomatous hypophysitis.

OBJECTIVE: To describe the clinical features of giant-cell granulomatous hypophysitis and to report on the results of corticosteroid treatment. METHODS: A case of giant-cell granulomatous hypophysitis is presented, and the pertinent literature is reviewed. RESULTS: A 41-year-old woman with anterior pituitary dysfunction had a pituitary mass that was 18 by 16 by 13 mm by magnetic resonance imaging. The pituitary stalk was thickened and enhanced after intravenous administration of gadolinium. A biopsy specimen that was obtained at transsphenoidal pituitary exploration revealed that the patient had giant-cell granulomatous hypophysitis, a rare inflammatory pituitary disorder. High-dose corticosteroid therapy failed to reverse her anterior pituitary dysfunction. CONCLUSION: The coincidence of a contrast-enhancing pituitary mass with a thickened pituitary stalk and the awareness of the rare occurrence of endocrine inactive tumors in women of childbearing age should suggest an inflammatory pituitary condition. Such lesions should also be suspected in otherwise healthy young women with hypopituitarism and no evidence of hormone hypersecretion. On the basis of the literature and our experience, corticosteroid treatment does not seem to improve anterior pituitary function.

Subacute diencephalic angioencephalopathy: biopsy diagnosis and radiological features of a rare entity.

Subacute diencephalic angioencephalopathy (SDAE) is a rare and fatal disease of unknown etiology that involves the thalami bilaterally. To date, there have been four cases reported, in which the diagnosis was established only after post mortem examination of the brain. We report two male patients, ages 69 and 41 years, who presented with progressive dementia and somnolence. Radiological evaluation revealed enhancing lesions involving both thalami. The differential diagnosis included a number of neoplastic, inflammatory and vascular processes. In both cases, pathological evaluation of biopsy specimens suggested the diagnosis of SDAE. Despite supportive care, the disease progressed rapidly and both patients died within weeks after initial presentation. The diagnosis was confirmed at autopsy in both cases. SDAE is a rare cause of bithalamic disease that can be mistaken for a neoplasm as well as a number of conditions that necessitate different treatment choices. The histopathological findings can establish the diagnosis when combined with radiological and clinical information. This report emphasizes the utility of stereotactic biopsy in early diagnosis of SDAE.

Practical value of Ki-67 and p53 labeling indexes in stereotactic biopsies of diffuse and pilocytic astrocytomas.

OBJECTIVE: Stereotactic biopsies are increasingly being used for the diagnosis and grading of astrocytomas, and there is a growing need to obtain maximum information from these tissue samples. In everyday practice, p53 protein and Ki-67 immunohistochemical analyses are the most frequently used ancillary studies to aid in diagnosis and grading, but their exact role is not clearly established. This study was undertaken to evaluate the practical value of these markers in stereotactic biopsy samples from diffuse astrocytomas as well as pilocytic astrocytomas. Methods/Results.-We analyzed the Ki-67 (MIB-1) and p53 labeling indexes in the stereotactic biopsy specimens from 11 pilocytic astrocytomas; 8 grade 2, 15 grade 3, and 16 grade 4 diffuse astrocytomas. Pilocytic astrocytomas and diffuse astrocytomas were evaluated as 2 separate groups. There was a strong correlation with poor outcome when both labeling indexes were higher than 15% in the same tumor for diffuse astrocytomas (P < 0.01). The indexes did not correlate with outcome in pilocytic astrocytomas. CONCLUSION: Combined Ki-67 and p53 labeling indexes higher than 15% indicated a worse outcome than suggested by the histologic grading. The analysis aided or improved histologic evaluation of stereotactic biopsies in our patients. We believe that a realistic prognostic upgrading of diffuse astrocytomas should be made only when labeling indexes for both markers are greater than 15%.