HMGA2: A biomarker significantly overexpressed in high-grade ovarian serous carcinoma

被引:78
作者
Mahajan, Aparna
Liu, Zhaojian
Gellert, Lan [2 ]
Zou, Xuanyi [2 ]
Yang, Guangyu [3 ]
Lee, Peng [2 ]
Yang, Ximing [3 ]
Wei, Jian-Jun [1 ,3 ]
机构
[1] Northwestern Univ, Dept Pathol, SOM, Feinberg Sch Med, Chicago, IL 60611 USA
[2] NYU, Sch Med, Dept Pathol, New York, NY USA
[3] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
关键词
ovarian carcinoma; papillary serous carcinoma; HMGA2; p53; immunohistochemistry; CANCER; EXPRESSION; LET-7; GENE; ADENOCARCINOMA; TRANSFORMATION; ENDOMETRIOSIS; PATHOGENESIS; THERAPY; TISSUES;
D O I
10.1038/modpathol.2010.49
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Ovarian carcinoma consists of a group of histologically heterogeneous diseases involving distinct tumorigenic pathways. High-grade papillary serous carcinoma of the ovary is commonly associated with p53 mutations. HMGA2, an oncofetal protein, is found to be overexpressed in ovarian cancer. To study the function of HMGA2 in ovarian cancer, it is important to know which subtypes of ovarian cancer are associated with HMGA2 overexpression. In this study, we collected six different types of ovarian cancer and examined HMGA2 expression by immunohistochemistry, along with HMGA1, p53 and Ki-67. We found that HMGA2 overexpression was significantly higher in high-grade papillary serous carcinoma (64%) and carcinosarcoma (60%) than in other types of ovarian cancers (7-23%). HMGA2 overexpression was moderately associated with dominant p53 mutations (R = 0.51). In addition, the microRNA in situ analysis revealed that let-7b, the HMGA2-negative regulators, were significantly lost in high-grade serous carcinoma. Our findings suggest that HMGA2 is an important molecular change significantly related to high-grade papillary serous carcinoma and is less common in other histological types of ovarian cancer. Modern Pathology (2010) 23, 673-681; doi: 10.1038/modpathol.2010.49; published online 12 March 2010
引用
收藏
页码:673 / 681
页数:9
相关论文
共 31 条
[1]  
*AM CANC SOC, 2008, CANC FACTS FIG 200
[2]  
BERLINGIERI MT, 1995, MOL CELL BIOL, V15, P1545
[3]   Roles of HMGA proteins in cancer [J].
Fusco, Alfredo ;
Fedele, Monica .
NATURE REVIEWS CANCER, 2007, 7 (12) :899-910
[4]  
Gattas GJF, 1999, GENE CHROMOSOME CANC, V25, P316, DOI 10.1002/(SICI)1098-2264(199908)25:4<316::AID-GCC2>3.3.CO
[5]  
2-S
[6]   Pathogenetic Pathways in Ovarian Endometrioid Adenocarcinoma A Molecular Study of 29 Cases [J].
Geyer, Julia Turbiner ;
Angeles Lopez-Garcia, Maria ;
Sanchez-Estevez, Carolina ;
Sarrio, David ;
Moreno-Bueno, Gema ;
Franceschetti, Ilaria ;
Palacios, Jose ;
Oliva, Esther .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2009, 33 (08) :1157-1163
[7]   HMGA2 protein expression correlates with lymph node metastasis and increased tumor grade in pancreatic ductal adenocarcinoma [J].
Hristov, Alexandra C. ;
Cope, Leslie ;
Delos Reyes, Marcelo ;
Singh, Mansher ;
Iacobuzio-Donahue, Christine ;
Maitra, Anirban ;
Resar, L. M. S. .
MODERN PATHOLOGY, 2009, 22 (01) :43-49
[8]   Substrate requirements for let-7 function in the developing zebrafish embryo [J].
Kloosterman, WP ;
Wienholds, E ;
Ketting, RF ;
Plasterk, RHA .
NUCLEIC ACIDS RESEARCH, 2004, 32 (21) :6284-6291
[9]   Ovarian Carcinoma Subtypes Are Different Diseases: Implications for Biomarker Studies [J].
Koebel, Martin ;
Kalloger, Steve E. ;
Boyd, Niki ;
McKinney, Steven ;
Mehl, Erika ;
Palmer, Chana ;
Leung, Samuel ;
Bowen, Nathan J. ;
Ionescu, Diana N. ;
Rajput, Ashish ;
Prentice, Leah M. ;
Miller, Dianne ;
Santos, Jennifer ;
Swenerton, Kenneth ;
Gilks, C. Blake ;
Huntsman, David .
PLOS MEDICINE, 2008, 5 (12) :1749-1760
[10]   Pathogenesis of ovarian cancer: Lessons from morphology and molecular biology and their clinical implications [J].
Kurman, Robert J. ;
Shih, Ie-Ming .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY, 2008, 27 (02) :151-160