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dc.contributor.authorMcGrogan, Barbara
dc.contributor.authorPhelan, Sine
dc.contributor.authorFitzpatrick, Patricia
dc.contributor.authorMaguire, Aoife
dc.contributor.authorPrencipe, Maria
dc.contributor.authorBrennan, Donal
dc.contributor.authorDoyle, Emma
dc.contributor.authorO'Grady, Anthony
dc.contributor.authorKay, Elaine
dc.contributor.authorFurlong, Fiona
dc.contributor.authorMcCann, Amanda
dc.date.accessioned2014-10-15T14:00:25Z
dc.date.available2014-10-15T14:00:25Z
dc.date.issued2014-07
dc.identifier.citationMcGrogan B et al. Spindle assembly checkpoint protein expression correlates with cellular proliferation and shorter time to recurrence in ovarian cancer. Hum. Pathol. 2014, 45 (7):1509-19en_GB
dc.identifier.issn1532-8392
dc.identifier.pmid24792619
dc.identifier.doi10.1016/j.humpath.2014.03.004
dc.identifier.urihttp://hdl.handle.net/10147/332805
dc.description.abstractOvarian carcinoma (OC) is the most lethal of the gynecological malignancies, often presenting at an advanced stage. Treatment is hampered by high levels of drug resistance. The taxanes are microtubule stabilizing agents, used as first-line agents in the treatment of OC that exert their apoptotic effects through the spindle assembly checkpoint. BUB1-related protein kinase (BUBR1) and mitotic arrest deficient 2 (MAD2), essential spindle assembly checkpoint components, play a key role in response to taxanes. BUBR1, MAD2, and Ki-67 were assessed on an OC tissue microarray platform representing 72 OC tumors of varying histologic subtypes. Sixty-one of these patients received paclitaxel and platinum agents combined; 11 received platinum alone. Overall survival was available for all 72 patients, whereas recurrence-free survival (RFS) was available for 66 patients. Increased BUBR1 expression was seen in serous carcinomas, compared with other histologies (P = .03). Increased BUBR1 was significantly associated with tumors of advanced stage (P = .05). Increased MAD2 and BUBR1 expression also correlated with increased cellular proliferation (P < .0002 and P = .02, respectively). Reduced MAD2 nuclear intensity was associated with a shorter RFS (P = .03), in ovarian tumors of differing histologic subtype (n = 66). In this subgroup, for those women who received paclitaxel and platinum agents combined (n = 57), reduced MAD2 intensity also identified women with a shorter RFS (P < .007). For the entire cohort of patients, irrespective of histologic subtype or treatment, MAD2 nuclear intensity retained independent significance in a multivariate model, with tumors showing reduced nuclear MAD2 intensity identifying patients with a poorer RFS (P = .05).
dc.language.isoenen
dc.rightsArchived with thanks to Human pathologyen_GB
dc.subjectCANCERen_GB
dc.subjectWOMEN'S HEALTHen_GB
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshCarcinoma
dc.subject.meshCell Proliferation
dc.subject.meshDisease-Free Survival
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshM Phase Cell Cycle Checkpoints
dc.subject.meshMad2 Proteins
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Recurrence, Local
dc.subject.meshOvarian Neoplasms
dc.subject.meshPrognosis
dc.subject.meshProtein-Serine-Threonine Kinases
dc.subject.meshSurvival Rate
dc.subject.meshTime Factors
dc.subject.otherCANCER, OVARIANen_GB
dc.titleSpindle assembly checkpoint protein expression correlates with cellular proliferation and shorter time to recurrence in ovarian cancer.en_GB
dc.typeArticleen
dc.contributor.departmentUCD School of Medicine and Medical Science, University College Dublin, UCD, Belfield, Dublin 4, Ireland; UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland; National Cancer Control Programme, King's Inns House, Dublin 1, Ireland. Electronic address: Barbara.mc-grogan@ucdconnect.ie.en_GB
dc.identifier.journalHuman pathologyen_GB
dc.description.fundingOtheren
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen
html.description.abstractOvarian carcinoma (OC) is the most lethal of the gynecological malignancies, often presenting at an advanced stage. Treatment is hampered by high levels of drug resistance. The taxanes are microtubule stabilizing agents, used as first-line agents in the treatment of OC that exert their apoptotic effects through the spindle assembly checkpoint. BUB1-related protein kinase (BUBR1) and mitotic arrest deficient 2 (MAD2), essential spindle assembly checkpoint components, play a key role in response to taxanes. BUBR1, MAD2, and Ki-67 were assessed on an OC tissue microarray platform representing 72 OC tumors of varying histologic subtypes. Sixty-one of these patients received paclitaxel and platinum agents combined; 11 received platinum alone. Overall survival was available for all 72 patients, whereas recurrence-free survival (RFS) was available for 66 patients. Increased BUBR1 expression was seen in serous carcinomas, compared with other histologies (P = .03). Increased BUBR1 was significantly associated with tumors of advanced stage (P = .05). Increased MAD2 and BUBR1 expression also correlated with increased cellular proliferation (P < .0002 and P = .02, respectively). Reduced MAD2 nuclear intensity was associated with a shorter RFS (P = .03), in ovarian tumors of differing histologic subtype (n = 66). In this subgroup, for those women who received paclitaxel and platinum agents combined (n = 57), reduced MAD2 intensity also identified women with a shorter RFS (P < .007). For the entire cohort of patients, irrespective of histologic subtype or treatment, MAD2 nuclear intensity retained independent significance in a multivariate model, with tumors showing reduced nuclear MAD2 intensity identifying patients with a poorer RFS (P = .05).


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