Spindle assembly checkpoint protein expression correlates with cellular proliferation and shorter time to recurrence in ovarian cancer.

Hdl Handle:
http://hdl.handle.net/10147/332805
Title:
Spindle assembly checkpoint protein expression correlates with cellular proliferation and shorter time to recurrence in ovarian cancer.
Authors:
McGrogan, Barbara; Phelan, Sine; Fitzpatrick, Patricia; Maguire, Aoife; Prencipe, Maria; Brennan, Donal; Doyle, Emma; O'Grady, Anthony; Kay, Elaine; Furlong, Fiona; McCann, Amanda
Affiliation:
UCD 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.
Citation:
McGrogan 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):1509-19
Journal:
Human pathology
Issue Date:
Jul-2014
URI:
http://hdl.handle.net/10147/332805
DOI:
10.1016/j.humpath.2014.03.004
PubMed ID:
24792619
Abstract:
Ovarian 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).
Item Type:
Article
Language:
en
Keywords:
CANCER; WOMEN'S HEALTH
Local subject classification:
CANCER, OVARIAN
MeSH:
Adult; Aged; Carcinoma; Cell Proliferation; Disease-Free Survival; Female; Humans; M Phase Cell Cycle Checkpoints; Mad2 Proteins; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Prognosis; Protein-Serine-Threonine Kinases; Survival Rate; Time Factors
ISSN:
1532-8392

Full metadata record

DC FieldValue Language
dc.contributor.authorMcGrogan, Barbaraen_GB
dc.contributor.authorPhelan, Sineen_GB
dc.contributor.authorFitzpatrick, Patriciaen_GB
dc.contributor.authorMaguire, Aoifeen_GB
dc.contributor.authorPrencipe, Mariaen_GB
dc.contributor.authorBrennan, Donalen_GB
dc.contributor.authorDoyle, Emmaen_GB
dc.contributor.authorO'Grady, Anthonyen_GB
dc.contributor.authorKay, Elaineen_GB
dc.contributor.authorFurlong, Fionaen_GB
dc.contributor.authorMcCann, Amandaen_GB
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).en_GB
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

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