Molecular determinants of invasion in endometrial cancer

Abal, Miguel; Llauradó, Marta; Doll, Andreas; Monge, Marta; Colás, Eva; González, Marta; Rigau, Marina; Alazzouzi, Hafid; Demajo, Santiago; Castellví, Josep; Garcia, Arnald; Cajal, S. Ramón y; Xercavins, Jordi; Vazquez‐Levin, Mónica H.; Alameda, Francesc; Gil‐Moreno, Antonio; Reventós, Jaume

doi:10.1007/s12094-007-0054-z

Cited by 37 publications

(43 citation statements)

References 55 publications

(51 reference statements)

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“…10 and EPS8L2 in representative examples of endometrial carcinoma (upper panels). Specific staining at tumor glands (T) in contrast to faint labeling in normal glands (n) and stroma (st) in different histological types including endometrioid (1,3,4,5,6,7,8), serous (2) and clear cell (9) carcinomas. Western blot analysis of P4HB in paired samples including tumor tissue (T) and adjacent normal endometrium (N) from four different patients.…”

Section: Early Detection and Diagnosismentioning

confidence: 99%

“…3 Type I cancers are typically known to have alterations in PTEN, KRAS2, DNA mismatch repair defects, CTNNB1, and have near diploid karyotype. Type II cancers typically have TP53 mutations and ErBB2 overexpression and are mostly nondiploid.…”

Section: Early Detection and Diagnosismentioning

confidence: 99%

“…In addition, new methods for prognosis and classification of EC are needed to combat this deadly disease. 3 Focusing on early detection, there is a necessity for screening methods with high sensitivity and specificity. To date, no characterized molecular marker has been validated for the diagnosis of EC.…”

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confidence: 99%

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Molecular markers of endometrial carcinoma detected in uterine aspirates

Colás¹,

Pérez

Cabrera

et al. 2011

Intl Journal of Cancer

108

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Endometrial cancer (EC) is the most frequent of the invasive tumors of the female genital tract. Although usually detected in its initial stages, a 20% of the patients present with advanced disease. To date, no characterized molecular marker has been validated for the diagnosis of EC. In addition, new methods for prognosis and classification of EC are needed to combat this deadly disease. We thus aimed to identify new molecular markers of EC and to evaluate their validity on endometrial aspirates. Gene expression screening on 52 carcinoma samples and series of real‐time quantitative PCR validation on 19 paired carcinomas and normal tissue samples and on 50 carcinoma and noncarcinoma uterine aspirates were performed to identify and validate potential biomarkers of EC. Candidate markers were further confirmed at the protein level by immunohistochemistry and Western blot. We identified ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2 and DCN as differentially expressed in ECs. Furthermore, the differential expression of these biomarkers in primary endometrial tumors is correlated to their expression level in corresponding uterine fluid samples. Finally, these biomarkers significantly identified EC with area under the receiver‐operating‐characteristic values ranging from 0.74 to 0.95 in uterine aspirates. Interestingly, analogous values were found among initial stages. We present the discovery of molecular biomarkers of EC and describe their utility in uterine aspirates. These findings represent the basis for the development of a highly sensitive and specific minimally invasive method for screening ECs.

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Section: Early Detection and Diagnosismentioning

confidence: 99%

Section: Early Detection and Diagnosismentioning

confidence: 99%

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Molecular markers of endometrial carcinoma detected in uterine aspirates

Colás¹,

Pérez

Cabrera

et al. 2011

Intl Journal of Cancer

108

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“…endometrial carcinoma spreads primarily to the pelvic and paraaortic lymph nodes, as well as to the adnexa and pelvic viscera, with distant metastases via the hematogenous route having a low incidence. The mechanisms involved in this aggressive transformation and dissemination are largely unknown (5).…”

Section: Introductionmentioning

confidence: 99%

High-Risk Endometrial Carcinoma Profiling Identifies TGF-β1 as a Key Factor in the Initiation of Tumor Invasion

Muinelo‐Romay

Colás

Barbazán

et al. 2011

Molecular Cancer Therapeutics

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Endometrial cancer is among the three most common cancers in females in industrialized countries. In the majority of cases, the tumor is confined to the uterus at the time of diagnosis and presents a good prognosis. However, after primary surgery, 15% to 20% of these tumors recur and have limited response to systemic therapy. We carried out gene expression profiling of high-risk recurrence endometrial cancers to identify new therapeutic approaches targeting the molecular pathways involved in the acquisition of an aggressive tumor phenotype. A microarray gene-expression analysis on a total of 51 human endometrial carcinomas revealed 77 genes specifically altered in high-risk recurrence tumors (P < 0.001). The bioinformatics analysis of gene-gene interactions and molecular relationships among these genes pointed to a prominent role for TGFb1 signaling in the acquisition of an aggressive phenotype. We further showed that TGF-b1 has a principal role at the initiation of endometrial carcinoma invasion through the promotion of the epithelial to mesenchymal transition that leads to the acquisition of an invasive phenotype in HEC-1A and RL95-2 cells. Impairment of this initial step with SB-431542, a specific TGF-b1 inhibitor, precluded further persistent endometrial carcinoma invasion. In conclusion, we showed that the characterization of the molecular changes associated with the acquisition of an aggressive phenotype represents a realistic strategy for the rational identification and characterization of new potential therapeutic targets in an effort to improve the clinical management and the outcome of high-risk endometrial cancer patients. Mol Cancer Ther; 10(8); 1357-66. '2011 AACR.

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“…Tumors of comparable size and histology can have widely divergent metastatic potential, depending on their genotype and local environmental influences. Metastatic potential is influenced by the local microenvironment, angiogenesis, stroma-tumor interactions, and elaboration of cytokines by the local tissue, and more significantly by its molecular phenotype [36,37]. Specific genetic alterations in cellular adhesion molecules, among them the cadherins and catenins, are important for such tumor-stroma and tumor-vascular interactions [38].…”

Section: Invasion and Metastasismentioning

confidence: 99%