Molecular pathology of endometrial carcinoma

This review paper discusses the main molecular alterations of endometrial carcinoma, the most common cancer of the female genital tract. Two clinicopathological variants are recognized: the oestrogen‐related (type I, endometrioid carcinoma) and the non‐oestrogen‐related (type II, non‐endometrioid carcinoma). Whereas type I shows microsatellite instability and mutations in PTEN, PIK3CA, K‐RAS and CTNNB1 (beta‐catenin), type II exhibits TP53 mutations and chromosomal instability. Recent investigations regarding the role of non‐coding RNA have provided important information regarding tumour progression. Understanding pathogenesis at the molecular level is essential for identifying biomarkers of potential use in targeted therapies.

[1]  E. Oliva,et al.  Molecular events in endometrial carcinosarcomas and the role of high mobility group AT-hook 2 in endometrial carcinogenesis. , 2013, Human pathology.

[2]  J. Valls,et al.  Blockade of NFκB activity by Sunitinib increases cell death in Bortezomib‐treated endometrial carcinoma cells , 2012, Molecular oncology.

[3]  K. Shroyer,et al.  Prognostic Significance of miR-205 in Endometrial Cancer , 2012, Biomarker Research.

[4]  E. Oliva,et al.  Immunohistochemical features of post‐radiation vaginal recurrences of endometrioid carcinomas of the endometrium: role for proteins involved in resistance to apoptosis and hypoxia , 2012, Histopathology.

[5]  Joan Valls,et al.  FGFR2 alterations in endometrial carcinoma , 2011, Modern Pathology.

[6]  J. Inazawa,et al.  miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer. , 2011, Cancer research.

[7]  M. Goodheart,et al.  Toward a microRNA signature of endometrial cancer , 2011 .

[8]  S. Wiseman,et al.  Loss of BAF250a (ARID1A) is frequent in high‐grade endometrial carcinomas , 2011, The Journal of pathology.

[9]  D. Sgroi,et al.  PIK3R1 (p85α) is somatically mutated at high frequency in primary endometrial cancer. , 2011, Cancer research.

[10]  H. Aburatani,et al.  Genotype-dependent efficacy of a dual PI3K/mTOR inhibitor, NVP-BEZ235, and an mTOR inhibitor, RAD001, in endometrial carcinomas. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  E. Oliva,et al.  Nuclear factor-κB2/p100 promotes endometrial carcinoma cell survival under hypoxia in a HIF-1α independent manner , 2011, Laboratory Investigation.

[12]  I. Shih,et al.  Mutation and Loss of Expression of ARID1A in Uterine Low-grade Endometrioid Carcinoma , 2011, The American journal of surgical pathology.

[13]  Robert E. Lewis,et al.  KSR1 is overexpressed in endometrial carcinoma and regulates proliferation and TRAIL-induced apoptosis by modulating FLIP levels. , 2011, The American journal of pathology.

[14]  J. Valls,et al.  Promoter hypermethylation and expression of sprouty 2 in endometrial carcinoma. , 2011, Human pathology.

[15]  D. Sgroi,et al.  A Unique Spectrum of Somatic PIK3CA (p110α) Mutations Within Primary Endometrial Carcinomas , 2011, Clinical Cancer Research.

[16]  E. Oliva,et al.  Micro‐RNA signature of the epithelial–mesenchymal transition in endometrial carcinosarcoma , 2011, The Journal of pathology.

[17]  Yusuke Kobayashi,et al.  MicroRNA and endometrial cancer: Roles of small RNAs in human tumors and clinical applications (Review). , 2010, Oncology letters.

[18]  A. Ashworth,et al.  PTEN Deficiency in Endometrioid Endometrial Adenocarcinomas Predicts Sensitivity to PARP Inhibitors , 2010, Science Translational Medicine.

[19]  J. Weidhaas,et al.  MicroRNA signatures differentiate uterine cancer tumor subtypes. , 2010, Gynecologic oncology.

[20]  P. Pandolfi,et al.  A coding-independent function of gene and pseudogene mRNAs regulates tumour biology , 2010, Nature.

[21]  L. Tafe,et al.  Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms , 2010, Modern Pathology.

[22]  N. Eritja,et al.  The multikinase inhibitor Sorafenib induces apoptosis and sensitises endometrial cancer cells to TRAIL by different mechanisms. , 2010, European journal of cancer.

[23]  J. Prat,et al.  Expression profiling of 22 genes involved in the PI3K–AKT pathway identifies two subgroups of high-grade endometrial carcinomas with different molecular alterations , 2010, Modern Pathology.

[24]  L. Ellenson,et al.  Molecular alterations in uterine serous carcinoma. , 2010, Gynecologic oncology.

[25]  L. Ellenson,et al.  Molecular alterations of EGFR and PIK3CA in uterine serous carcinoma. , 2009, Gynecologic oncology.

[26]  J. Prat,et al.  Concomitant PI3K–AKT and p53 alterations in endometrial carcinomas are associated with poor prognosis , 2009, Modern Pathology.

[27]  N. Eritja,et al.  Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints , 2008, Journal of Clinical Pathology.

[28]  J. Baselga,et al.  NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. , 2008, Cancer research.

[29]  Kristian Cibulskis,et al.  Drug-sensitive FGFR2 mutations in endometrial carcinoma , 2008, Proceedings of the National Academy of Sciences.

[30]  N. Eritja,et al.  Promoter hypermethylation and reduced expression of RASSF1A are frequent molecular alterations of endometrial carcinoma , 2008, Modern Pathology.

[31]  N. Eritja,et al.  CK2 controls TRAIL and Fas sensitivity by regulating FLIP levels in endometrial carcinoma cells , 2008, Oncogene.

[32]  David I. Smith,et al.  Long, abundantly expressed non-coding transcripts are altered in cancer. , 2008, Human molecular genetics.

[33]  J. Prat,et al.  PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters , 2008, Modern Pathology.

[34]  P. Pollock,et al.  Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes , 2007, Oncogene.

[35]  J. Prat,et al.  Endometrial carcinoma: pathology and genetics. , 2007, Pathology.

[36]  P. Pandolfi,et al.  Essential Role for Nuclear PTEN in Maintaining Chromosomal Integrity , 2007, Cell.

[37]  X. Matías-Guiu,et al.  PIK3CA gene mutations in endometrial carcinoma: correlation with PTEN and K-RAS alterations. , 2006, Human pathology.

[38]  X. Matías-Guiu,et al.  Proteasome Inhibitors Induce Death but Activate NF-κB on Endometrial Carcinoma Cell Lines and Primary Culture Explants* , 2006, Journal of Biological Chemistry.

[39]  G. Moreno-Bueno,et al.  Low Frequency of BRAF Mutations in Endometrial and in Cervical Carcinomas , 2006, Clinical Cancer Research.

[40]  C. Morrison,et al.  HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  Frank McCormick,et al.  High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. , 2005, Cancer research.

[42]  M. Rue,et al.  FLIP is frequently expressed in endometrial carcinoma and has a role in resistance to TRAIL-induced apoptosis , 2005, Laboratory Investigation.

[43]  A. Berchuck,et al.  Gene expression profiling of microsatellite unstable and microsatellite stable endometrial cancers indicates distinct pathways of aberrant signaling. , 2005, Cancer research.

[44]  A. Berchuck,et al.  Microarray Analysis of Endometrial Carcinomas and Mixed Mullerian Tumors Reveals Distinct Gene Expression Profiles Associated with Different Histologic Types of Uterine Cancer , 2005, Clinical Cancer Research.

[45]  M. Rue,et al.  Abnormalities in the NF‐κB family and related proteins in endometrial carcinoma , 2004 .

[46]  N. Socci,et al.  Distinctive Gene Expression Profiles by cDNA Microarrays in Endometrioid and Serous Carcinomas of the Endometrium , 2004, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[47]  J. Cigudosa,et al.  Differential gene expression profile in endometrioid and nonendometrioid endometrial carcinoma: STK15 is frequently overexpressed and amplified in nonendometrioid carcinomas. , 2003, Cancer research.

[48]  J. Herman,et al.  Abnormalities of the APC/β-catenin pathway in endometrial cancer , 2002, Oncogene.

[49]  X. Matías-Guiu,et al.  CTNNB1 mutations and β-catenin expression in endometrial carcinomas , 2002 .

[50]  A. García,et al.  Molecular pathology of endometrial hyperplasia and carcinoma. , 2001, Human pathology.

[51]  X. Matías-Guiu,et al.  K‐ras mutations in endometrial carcinomas with microsatellite instability , 2001, The Journal of pathology.

[52]  C. Eng,et al.  Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. , 2000, Journal of the National Cancer Institute.

[53]  X. Matías-Guiu,et al.  Frameshift mutations at coding mononucleotide repeat microsatellites in endometrial carcinoma with microsatellite instability , 2000, Cancer.

[54]  X. Matías-Guiu,et al.  PTEN mutations in endometrial carcinomas: a molecular and clinicopathologic analysis of 38 cases. , 2000, Human pathology.

[55]  J. Herman,et al.  hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis. , 1999, The American journal of pathology.

[56]  T. Tokino,et al.  Mutations of the β‐Catenin Gene in Endometrial Carcinomas , 1999, Japanese journal of cancer research : Gann.

[57]  X. Matías-Guiu,et al.  BAX somatic frameshift mutations in endometrioid adenocarcinomas of the endometrium: evidence for a tumor progression role in endometrial carcinomas with microsatellite instability. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[58]  X. Matías-Guiu,et al.  Microsatellite instability in endometrial carcinomas: clinicopathologic correlations in a series of 42 cases. , 1998, Human pathology.

[59]  S. Hirohashi,et al.  Beta-catenin mutation in carcinoma of the uterine endometrium. , 1998, Cancer research.

[60]  Kathleen R. Cho,et al.  Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. , 1997, Cancer research.

[61]  M. Pieretti,et al.  Loss of heterozygosity in usual and special variant carcinomas of the endometrium. , 1997, Human pathology.

[62]  S. Sato,et al.  Deletion mapping on chromosome 10q25-q26 in human endometrial cancer. , 1996, British Journal of Cancer.

[63]  M. Sherman,et al.  p53 in endometrial cancer and its putative precursors: evidence for diverse pathways of tumorigenesis. , 1995, Human pathology.

[64]  Y. Nakamura,et al.  Microsatellite instability in endometrial carcinomas: Frequent replication errors in tumors of early onset and/or of poorly differentiated type , 1995, Genes, chromosomes & cancer.

[65]  D. Shibata,et al.  Microsatellite instability in sporadic endometrial carcinoma. , 1994, Journal of the National Cancer Institute.

[66]  A. Berchuck,et al.  Genetic instability of microsatellites in endometrial carcinoma. , 1993, Cancer research.

[67]  J. V. Bokhman.  Two pathogenetic types of endometrial carcinoma. , 1983, Gynecologic oncology.

[68]  N. Eritja,et al.  CK2beta is expressed in endometrial carcinoma and has a role in apoptosis resistance and cell proliferation. , 2009, The American journal of pathology.

[69]  Amir Jazaeri,et al.  Microarray analysis reveals distinct gene expression profiles among different histologic types of endometrial cancer. , 2003, Cancer research.

[70]  X. Matías-Guiu,et al.  CTNNB1 mutations and beta-catenin expression in endometrial carcinomas. , 2002, Human pathology.

[71]  J. Herman,et al.  Abnormalities of the APC/beta-catenin pathway in endometrial cancer. , 2002, Oncogene.

[72]  X. Matías-Guiu,et al.  Beta- and gamma-catenin expression in endometrial carcinoma. Relationship with clinicopathological features and microsatellite instability. , 2001, Virchows Archiv : an international journal of pathology.

[73]  Kathleen R. Cho,et al.  p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis. , 1997, The American journal of pathology.