UNASSIGNED: 291 Background: DNA repair factors are hypothesized to mediate chemosensitivity to cytotoxic agents that produce DNA damage and may be predictive for response to @entity902 -based chemotherapeutic regimens. Primary @entity189 ( @entity189 ) @entity5 of @entity1 who developed @entity3 were evaluated for expression of a panel of DNA repair factors by immunohistochemistry (IHC). METHODS: A cohort of 132 clinically annotated, uniformly-treated ( @entity902 -based combination chemotherapy) @entity189 @entity1 who subsequently developed distant metastases with FFPE primary @entity5 tissue available was identified. @entity5 bearing areas were evaluated by a single urologic pathologist. Tissue arrays were constructed for IHC analysis of the following DNA repair factors: @entity11833 , @entity6545 , @entity6069 , PAR and @entity12982 . @entity5 was deparaffinized and specific antigen retrieval determined for individual antibodies. Pathologist supervised IHC analysis of nuclear versus cytoplasmic expression was performed using spectral imaging analysis. @entity1349 ( @entity1349 ) was defined from start of chemotherapy for @entity3 to @entity204 (N=67) or censored on the last known alive date. Percent of positive nuclear staining was categorized as quartiles or previously identified cut-points. Cox regression evaluated the associations of percent positive nuclear staining levels and @entity1349 in multivariable analysis (HRs and 95% CIs included) that controlled for known prognostic variables (performance status and visceral metastases). RESULTS: Higher percentage of nuclear staining of @entity11833 [HR=2.7 (1.5, 4.9), p=0.0007]; @entity6545 [HR=5.6 (1.7, 18.3), p=0.005]; and PAR [HR=2.2 (1.1, 4.4), p=0.026] in @entity5 tissue were associated with poor outcome; each was independent of the other two repair factors and known prognostic variables. Neither nuclear nor cytoplasmic staining for @entity6069 or @entity12982 reached statistical significance for an association with @entity1349 . CONCLUSIONS: DNA damage repair factor levels measured by IHC impact outcomes in advanced @entity189 . External validation is ongoing and will be presented. Further studies are required to determine whether these biomarkers are prognostic or predictive in this setting.

Association of DNA repair factors with overall survival in advanced @entity189 treated with XXXX -based chemotherapy.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity11833 :: ('2067', 'Gene') :: ['ERCC1'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Tumor', 'tumors'] @entity189 :: ('MESH:D002277', 'Disease') :: ['urothelial carcinoma', 'UC'] @entity12982 :: ('142', 'Gene') :: ['PARP1'] @entity6069 :: ('672;675', 'Gene') :: ['BRCA1/2'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastatic disease'] @entity6545 :: ('5888', 'Gene') :: ['Rad 51', 'Rad51'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity902 :: ('MESH:D010984', 'Chemical') :: ['platinum'] @entity1349 :: ('MESH:D011475', 'Disease') :: ['OS', 'Overall survival']
@entity902 :: (MESH:D010984,Chemical) :: ['platinum']
