Identification of Novel Diagnostic Markers for Choroid Plexus Tumors

Hasselblatt, Martin; Böhm, C.; Tatenhorst, Lars; Dinh, Vinzenz; Newrzella, Dieter; Keyvani, Kathy; Jeibmann, Astrid; Buerger, Horst; Rickert, Christian H.; Paulus, Werner

doi:10.1097/01.pas.0000176430.88702.e0

Cited by 111 publications

(90 citation statements)

References 30 publications

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“…Some of the children had been examined as part of the Société Internationale d' Oncologie Pédiatrique choroid plexus tumor study (CPT-SIOP-2000). 18 All cases were reevaluated neuropathologically according to the current WHO criteria 4 including immunohistochemistry for INI1 19,20 as well as choroid plexus-specific markers. 20 Data on tumor location, extent of surgical resection, adjuvant treatment and postoperative course were compiled by reviewing patient records.…”

Section: Patientsmentioning

confidence: 99%

“…18 All cases were reevaluated neuropathologically according to the current WHO criteria 4 including immunohistochemistry for INI1 19,20 as well as choroid plexus-specific markers. 20 Data on tumor location, extent of surgical resection, adjuvant treatment and postoperative course were compiled by reviewing patient records. Moreover, general practitioners, pediatricians and neurosurgeons were contacted to provide follow-up information on recurrence and survival.…”

Section: Patientsmentioning

confidence: 99%

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Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas

et al. 2008

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Platelet-derived growth factor (PDGF) receptor signaling has been implicated in the development of glial tumors, but not yet been examined in choroid plexus carcinomas, pediatric tumors with dismal prognosis for which novel treatment options would be desirable. Therefore, protein expression of PDGF receptors a and b as well as amplification status of the respective genes, PDGFRA and PDGFRB, were examined in a series of 22 patients harboring choroid plexus carcinoma using immunohistochemistry and chromogenic in situ hybridization (CISH). The majority of choroid plexus carcinomas expressed PDGF receptors with 6 cases (27%) displaying high staining scores for PDGF receptor a and 13 cases (59%) showing high staining scores for PDGF receptor b. Correspondingly, copy-number gains of PDGFRA were observed in 8 cases out of 12 cases available for CISH and 1 case displayed amplification (six or more signals per nucleus). The proportion of choroid plexus carcinomas with amplification of PDGFRB was even higher (5/12 cases). PDGFRB amplification status and PDGF receptor b protein expression scores were significantly correlated (P ¼ 0.01, Spearman). Expression status of PDGF receptor a or PDGF receptor b was not significantly associated with progressionfree survival. To conclude, expression and amplification of PDGF receptors, particularly PDGF receptor b, are frequent in choroid plexus carcinomas, providing a first rationale for the development of treatments targeting PDGF receptor signaling in these rare malignant pediatric tumors.

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Section: Patientsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas

et al. 2008

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“…3,5,9 In human samples of CPTs, tissue microarray analysis has identified several candidate genes that are specific to choroid plexus and allow for differentiation from metastatic carcinomas. 2 One of these diagnostic markers is the inward rectifier potassium (K + ) channel Kir7.1, also known as inward rectifier potassium channel 13 or potassium inwardly rectifying channel, subfamily J, member 13.…”

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confidence: 99%

Kir7.1 immunoreactivity in canine choroid plexus tumors

2016

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Abstract. Choroid plexus neoplasms are uncommon brain tumors in dogs. Choroid plexus carcinomas often spread diffusely throughout the ventricular system and subarachnoid space and, in aggressive forms, can mimic histologic patterns of other carcinomas, including being embedded in a desmoplastic reaction. Although choroid plexus tumors (CPTs) heterogeneously express pan-cytokeratin, little is known about other markers to identify choroid plexus and their associated tumors. Kir7.1, an inward-rectifier potassium channel, is reported to have high diagnostic utility in human neuropathology to distinguish CPTs from other primary brain tumors and cerebral metastases. To determine Kir7.1 expression in the dog brain, we analyzed the immunoreactivity of Kir7.1 in normal brain, gliomas, ependymomas, CPTs, meningiomas, and carcinomas. In normal brain tissue, the immunostaining was restricted to the choroid plexus where there was robust membrane immunoreactivity along the apical border of the cells with less intense cytoplasmic staining. Similar strong immunoreactivity was detected in 12 of 12 CPTs, whereas 5 of 5 gliomas, 4 of 5 ependymomas, 5 of 5 meningiomas, and 5 of 6 carcinomas had no immunoreactivity. One ependymoma and 1 nasal carcinoma with squamous metaplasia were up to 75% immunopositive, with moderate cytoplasmic and membranous immunoreactivity, but lacking the robust apical immunoreactivity pattern. Analysis for immunoreactivity in a tissue microarray failed to yield any other locations in which immunoreactivity was detected. These results, including the distinctive pattern of immunostaining in CPTs, suggest that Kir7.1 is an excellent marker for CPTs in the dog.

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“…Imatinib, a tyrosine kinase inhibitor that targets PDGFR, was shown to decrease proliferation in the immortalized choroid plexus epithelial line Z310, suggesting it may play a role in future treatments [27]. The transcription factor TWIST1 is upregulated in CPPs compared to normal choroid plexus and is also found in the Z310 cell line [28]; decreasing its expression can decrease both infiltrative capacity and proliferative rate [29]. Current data suggests that activated Notch3 may function as an oncogene in the developing brain, driving choroid plexus tumor formation in utero [30].…”

Section: Discussionmentioning

confidence: 99%

Surgical outcomes in choroid plexus papillomas: an institutional experience

et al. 2013

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Choroid plexus papillomas (CPPs) are rare, indolent lesions that comprise less than 0.5 % of intracranial tumors. We sought to assess the long-term outcomes and associated surgical complications at our institution. A review of the University of California, San Francisco (UCSF) Brain Tumor Research Center (BTRC) database was performed to identify a cohort of patients treated for CPP from 1997 to 2011. Patients were grouped based on tumor location and extent of resection. Outcomes including progression-free survival and surgical complications were assessed. We identified 24 patients (16 female, 8 male) ranging in age from 6 months to 55 years (median 29 years) treated at our institution. Tumors were found in the following locations: 16 (67 %) fourth ventricle/cerebellopontine angle; 7 (29 %) lateral ventricle; 1 (4 %) third ventricle. Gross total resection (GTR) was achieved in 20 patients (83 %) with subtotal resection (STR) in 4 (17 %). Median follow-up time was 2.8 years with 3 recurrences identified at 1.6, 3.3, and 8.5 years. Extent of resection and tumor location were not associated with recurrence. There was one new permanent neurologic deficit detected after surgery. All patients were alive at most recent follow-up. Attempted gross total resection is the standard treatment for CPPs and generally associated with excellent outcomes. Since recurrences are rare, even among patients who undergo STR, radiation may be reserved for cases of tumor progression. This modern experience at a tertiary care center performed exclusively during the MRI-era demonstrates that CPPs can be safely removed with minimal morbidity and good tumor control.

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Identification of Novel Diagnostic Markers for Choroid Plexus Tumors

Cited by 111 publications

References 30 publications

Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas

Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas

Kir7.1 immunoreactivity in canine choroid plexus tumors

Surgical outcomes in choroid plexus papillomas: an institutional experience

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