title: HMGA2 protein expression in ovarian serous carcinoma effusions, primary tumors, and solid metastases.
abstract: The objective of this study was to analyze the expression and clinical role of the high mobility group AT hook (HMGA) protein in advanced-stage serous ovarian carcinoma. HMGA2 protein expression was investigated in 199 effusions and in 50 patient-matched primary tumors and solid metastases using immunohistochemistry. Results were analyzed for association with clinicopathologic parameters, including chemotherapy response, and survival. HMGA2 was expressed in tumor cells in 94.5 %, 96 %, and 90 % of specimens, respectively. There was no difference in HMGA2 expression between patient-matched samples from different anatomic sites (p > 0.3). HMGA2 expression in chemo-naïve samples was significantly higher in older patients (p = 0.006, p = 0.01, and p = 0.005 for effusions, primary tumors, and solid metastases, respectively). No association was found with residual disease volume. Furthermore, HMGA2 expression was not associated with FIGO stage (p > 0.2), except in chemo-naïve effusions (n = 106, p = 0.016). There was no difference in HMGA2 expression between chemo-naïve samples and samples obtained post-chemotherapy in effusions (p = 0.2) or primary tumors (p = 0.1). However, solid metastases obtained after chemotherapy exposure had higher HMGA2 expression compared with chemo-naïve samples (p = 0.032). HMGA2 expression was unrelated to chemotherapy response or survival. However, it was directly related to protein expression of the previously studied cancer stem cell marker Nestin (p = 0.01) and the gap junction protein claudin-7 (p = 0.02) and inversely related to the mRNA level of the E-cadherin repressor SIP1 (p = 0.02). This study provides evidence that HMGA2 is universally expressed in advanced-stage ovarian serous carcinoma irrespective of anatomic site, suggesting that HMGA2 may have a clinical role as therapeutic target.
authors.affiliation: Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, 0424 Oslo, Norway.
authors.forename: Thea Eline
authors.initials: TE
authors.lastname: Hetland
authors.forename: Arild
authors.initials: A
authors.lastname: Holth
authors.forename: Janne
authors.initials: J
authors.lastname: Kærn
authors.forename: Vivi Ann
authors.initials: VA
authors.lastname: Flørenes
authors.forename: Claes G
authors.initials: CG
authors.lastname: Tropé
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001202:Ascitic Fluid / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology; D005260:Female; D025743:HMGA2 Protein / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D016066:Pleural Effusion, Malignant / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D025743:HMGA2 Protein