Molecular Research On Invasiveness Of Craniopharyngioma And Clinical Analysis Of Seeding Metastasis

BackgroundCraniopharyngiomas are congenital tumors that locate in sellar region, twosubtypes with distinct clinical and pathological features were discribed: anadamantinomatous type and the other of squamous papillary type. Althoughhistologically benign and classified as tumoral grade Ⅰaccroding to2007WHOclassification of tumors of the central nervous system, craniopharyngiomas tend to actlike malignant ones. They may invade and widely adhere to surrounding vital neuroand vascular structures which making total removal very hard even to experiencedhands. Radical operations on craniopharyngiomas are complicated with relativelyhigh mortality and mobidity. Serious complications are common after surgery whichmaking poor long-term living quality very poor. Recurrence is common even aftergross total resection. In addition to local recurrence, rare cases of ectopic recurrencecannot be ignored which never happened in other sellar benign tumors. The tendencyto recur is a problem for neurosurgeons. Invasive behavior is the distinctive feature ofcraniopharyngioma, which is condisided to correlate with poor prognosis. Studyingthe molecular mechanism of invasive behaviors of craniopharyngioma will help fullyunderstand malignant behaviors of craniopharyngioma and further step down theincidence of postoperative recurrence and improve long–term prognosis.Part Ⅰ： Expression of14-3-3Zeta and correlation with invasiveness incraniopharyngiomaObjectTo research the expression of14-3-3Zeta in craniopharyngiomas and further explore its relationship with clinical and pathological feathers, invasiveness,proliferation for better recognize pathogenesis, proliferation and invasion bycomparing its expression level with aberrant expression of β-Catenin, p63and Ki-67.Try to investigate the mechanism of14-3-3Zeta in invasion of craniopharyngioma. Inorder to further understand this tumor would provide new clue for diagnose andtreatment of craniopharyngioma.MethodsRandomly select62cases of craniopharyngioma treated in our department betweenFebruary2012and August2013by including criterion. All patients receivedtranscranial operation and comfirmed the diagnosis by histopathological examinationpostoperatively. Collect clinical and pathological data of each case for furtherstudy.62tumors and4brain tissue fixed in paraffin were retrieved from tissue bank ofDepartment of Pathology. HE staining will be used to assess the morphologicalaspects of each tumor. Immunohistochemical examation will be adapted to assessexpression of14-3-3Zeta, β-Catenin, p63and Ki-67.Use immunoblotting (WesternBlot) to assess expression level of14-3-3Zeta in62tumor tissue and4brain tissuesnap froze during operation and reserved in-80℃.Use real-time PCR to assessexpression level of YWHAZ gene in20tumor tissue and4brain tissues.Collectclinical and pathological data of3cases of seeding metastatic craniopharyngiomastreated in our department. Perform thorough literature review and try to proposetechniques to reduce the risk of surgical seeding during operations.ResultsIn62cases included in present study,46of which were classified asadamantinomatous type and the other16as squamous papillary type using HEstaining according to2007WHO classification of tumors in central nervous system.27Invasive craniopharyngioma were detected out of46adamantinomatous tumors on the presence of multiple nests like ‘‘islands”or‘‘fingers’’ of tumor lie in glioticcerebral tissue while none was detected in16squamous papillary tumors.Immunostaining of14-3-3Zeta showed no statistical significance between twosubtypes for the expression level of this protein.14-3-3Zeta was expressedsignificantly higher in invasive adamantinomatous craniopharyngioma than in noneinvasive craniopharyngioma and squamous papillary type. There was no statisticalsignificance between noninvasive craniopharyngioma and squamous papillary typefor expression of14-3-3Zeta. Immunostaining of β-Catenin showed aberrantexpression of this protein in adamantinomatous subtype especially in invasive tumors.The incidence of aberrant expression of β-Catenin was significantly higher inadamantinomatous type than squamous papillary type. The incidence of aberrantexpression of β-Catenin was significantly higher in invasive tumors than noninvasiveones while the difference between noninvasive adamantinomatous type and squamouspapillary type was not statistically significant. Cells with strong staining of14-3-3Zeta shared similar distribution with cells aberrantly expressed β-Catenin, thatis, in whorl-like cell clusters located mainly in invasive front of adamantinomatoustumors. Immunostaining results of p63showed over expression in craniopharyngioma.There were no significant different between the two subtypes and between invasiveand noninvasive tumors. Immunostaining showed Ki-67positivity mainly restrictedto the peripherally palisading cells in adamantinomatous type and diffused insquamous papillary type. No correlation was found between Ki-67label index andinvasiveness. Craniopharyngioma showed aberrantβ-Catenin expression havesignificant higher level of expression of14-3-3Zeta. Western Blot showed significanthigher level of14-3-3Zeta expression in invasive adamantinomatouscraniopharyngioma than brain tissue while no statistical differernce were foundbetween invasive and noninvasive tumors. Real-time PCR showed higher level of PartⅡ：Clinical study of ectopic recurrent craniopharyngiomasObjectRetrospectively study clinical and pathological data of ectopic recurrentcraniopharyngiomas treated in our department. Investigate possible risk factor of thisrare entity by thoroughly reviewing published documents. Try to propose techniquesto reduce the risk of surgical seeding during operations.MethodsCollect clinical and pathological data of4cases of seeding metastaticcraniopharyngiomas treated in our department. Perform thorough literature reviewand try to propose techniques to reduce the risk of surgical seeding during operations.ResultsAll4cases are male adults,3of them are of papillary type with the other of YWHAZ gene transcription in craniopharyngioma than brain tissue while nostatistical differences were found between invasive and noninvasive tumors andbetween subtypes.Conlusions14-3-3Zeta is over expressed in craniopharyngioma and correlate with invasivenessbut not proliferation of this tumor. Over expression of14-3-3Zeta correlate withaberrant expression of β-Catenin both in diffusion and in expression level, indicating14-3-3Zeta over expression may mediate tumor invasiveness by regulating Wntcascade.Proliferation activity and expression of p63have no correlation withinvasiveness of craniopharyngioma. adamantinomatous. None of the cases had local recurrence during present admission.Ectopic recurrent craniopharyngioma showed no high level of cell proliferationdetermined by Ki-67label index. All ectopic tumors were located along previoussurgical tract which were attributed to surgical seeding.ConlusionsEctopc recurrence of craniopharyngioma is extremely rare. Cystic tumors shouldbe treated with extra caution to avoid dissemination and to prevent some degree ofectopic recurrence. Long time follow up is required even for patients with totallyremoved tumors since it may occur after a long tumor-free period. Good prognosiscould be achieved by early diagnosis and resection of ectopic recurrent tumor.