|Grant Number:||5R01CA116184-04 Interpret this number|
|Primary Investigator:||Kurman, Robert|
|Organization:||Johns Hopkins University|
|Project Title:||Pathogenesis of Ovarian Serous Borderline Tumors|
DESCRIPTION (provided by applicant): The objectives of this study are to assess the molecular genetic signatures of peritoneal implants associated with ovarian serous borderline tumors (SBTs) to determine if the molecular genetic changes can predict the clinical outcome in advanced stage SBTs. Since SBTs have a highly variable and unpredictable outcome, this study would have important implications in the clinical management of this disease. SBTs are a puzzling group of neoplasms that mainly occur in younger women. Their behavior is enigmatic, their pathogenesis unclear, and their clinical management controversial. Although SBTs are nearly always benign when tumor is confined to the ovary they are malignant in about 30% of cases when outside the ovary. These extraovarian tumors are termed "implants" because it is currently not known if the tumor implants represent i) a low-grade carcinoma that has metastasized from the primary ovarian tumor ii) an independent primary peritoneal carcinoma, or iii) a non-neoplastic benign peritoneal lesion. Based on our previous clinicopathologic studies, we hypothesize that: Peritoneal implants are not a single disease but a heterogeneous group of lesions. Molecular genetic analyses can characterize the different types of implants and when correlated with clinical outcome will distinguish these lesions better than the current morphologic classification. Our overall objective is to test these hypotheses by performing a comprehensive clinicopathologic and molecular genetic analysis of peritoneal implants that are associated with advanced stage SBTs collected from a nation-wide tumor registry in Denmark. The specific aims are as follows. Aim 1: Analyze the clinicopathologic features and behavior of SBTs with peritoneal implants from a nation-wide tumor registry. Aim 2: Analyze allelic imbalance in peritoneal implants and corresponding SBTs. Aim 3: Mutational analysis of protein kinases in peritoneal implants and corresponding SBTs. Aim 4: Determine the molecular genetic features of peritoneal implants and correlate them with clinical outcome. The results from this study will be translational as molecular profiling of implants and their associated SBTs with careful morphologic correlation will elucidate the molecular pathogenesis and behavior of SBTs at advanced stages. This will refine diagnostic and prognostic markers of advanced stage tumors. These results will be expected to have a significant impact on the clinical management of patients with this disease.