Overexpression of HMGA1 Figures as a Potential Prognostic Factor in Endometrioid Endometrial Carcinoma (EEC).

Endometrioid endometrial carcinomas (EEC) are the most common malignant gynecologic tumors. Despite the increase in EEC molecular knowledge, the identification of new biomarkers involved in disease's development and/or progression would represent an improvement in its course. High-mobility group A protein (HMGA) family members are frequently overexpressed in a wide range of malignancies, correlating with a poor prognosis. Thus, the aim of this study was to analyze HMGA1 and HMGA2 expression pattern and their potential role as EEC biomarkers. HMGA1 and HMGA2 expression was initially evaluated in a series of 46 EEC tumors (stages IA to IV), and the findings were then validated in The Cancer Genome Atlas (TCGA) EEC cohort, comprising 381 EEC tumors (stages IA to IV). Our results reveal that HMGA1 and HMGA2 mRNA and protein are overexpressed in ECC, but only HMGA1 expression is associated with increased histological grade and tumor size. Moreover, HMGA1 but not HMGA2 overexpression was identified as a negative prognostic factor to EEC patients. Finally, a positive correlation between expression of HMGA1 pseudogenes-HMGA1-P6 and HMGA1-P7-and HMGA1 itself was detected, suggesting HMGA1 pseudogenes may play a role in HMGA1 expression regulation in EEC. Thus, these results indicate that HMGA1 overexpression possesses a potential role as a prognostic biomarker for EEC.

UBE2C is overexpressed in ESCC tissues and its abrogation attenuates the malignant phenotype of ESCC cell lines.

The esophageal squamous cell carcinoma (ESCC) is widely known as a highly lethal and poor understood cancer, then requiring the search for novel molecular markers to improve its management and patients survival. Recently, ubiquitin-conjugating enzyme E2C (UBE2C) has been figuring as a prominent tumor biomarker candidate, once it has been recognized as a key player in cell cycle progression. In this way, the aim of this study was to evaluate the expression profile of UBE2C gene and protein in ESCC samples, as well as its diagnostic and prognostic marker potential, and its contribution to ESSC genesis and/or progression by performing in vitro functional assays. The analysis of UBE2C gene expression in 52 paired ESCC samples (tumor and respective histologically normal surrounding tissue), by qRT-PCR, revealed that this gene is overexpressed in 73% of ESCC samples. Subsequently, immunohistochemical analysis confirmed that UBE2C protein expression was upregulated in all ESCC cases, but absent in the histologically normal tumor surrounding tissues. Moreover, we showed that UBE2C mRNA expression was able to accurately discriminate ESCC tissue from both healthy esophageal and histologically normal tumor surrounding tissues, pointing out its role as a diagnostic marker for this cancer. Finally, we report that UBE2C affects proliferation rates and cell cycle profile of ESCC cell lines, by directly interfering with cyclin B1 protein levels, suggesting its involvement in crucial steps of ESCC carcinogenesis.

HMGA2 overexpression plays a critical role in the progression of esophageal squamous carcinoma.

Esophageal Squamous Cell Carcinoma (ESCC) is the most common esophageal tumor worldwide. However, there is still a lack of deeper knowledge about biological alterations involved in ESCC development. High Mobility Group A (HMGA) protein family has been related with poor outcome and malignant cell transformation in several tumor types. In this way, the aim of this study was to analyze the expression of HMGA1 and HMGA2 expression in ESCC and their role in crucial cellular features. We evaluated HMGA1 and HMGA2 mRNA expression in 52 paired ESCC and normal surrounding tissue samples by qRT-PCR. Here, we show that HMGA2, but not HMGA1, is overexpressed in ESCC samples. This result was further confirmed by the immunohistochemical analysis. Indeed, accordingly to mRNA expression data, HMGA2, but not HMGA1, was overexpressed in approximately 90% of ESCC samples, while it was barely expressed in the respective control. Conversely, HMGA1, but not HMGA2, was overexpressed in esophageal adenocarcinoma samples. Interestingly, HMGA2 abrogation attenuated the malignant phenotype of two ESCC cell lines, suggesting that HMGA2 overexpression is involved in ESCC progression.

ERM/ETV5 and RUNX1/AML1 expression in endometrioid adenocarcinomas of endometrium and association with neoplastic progression.

The majority of endometrioid endometrial carcinomas (EEC) is diagnosed at stage I. Among these, 30% present myometrial invasion (stage IB), which is associated with tumor spread and relapse after primary treatment. Although an increased expression of RUNX1/AML1 and ERM/ETV5 in EEC have been suggested to be associated with early events of myometrial infiltration, there is no data regarding its expression along the evolution of EEC and possible associations with other clinicopathological parameters. Therefore, ERM/ETV5 and RUNX1/AML1 protein and gene expression profiles were assessed in different EEC stages to evaluate their role in endometrial carcinogenesis. RUNX1/AML1 and ERM/ETV5 proteins were analyzed by immunohistochemistry in 219 formalin fixed paraffin embedded endometrioid tumors and in 12 normal atrophic and proliferative endometrium samples. RUNX1/AML1 and ERM/ETV5 genes expression were analyzed by RT-qPCR. RUNX1/AML1 and ERM/ETV5 expression were decreased with increasing EEC stage, with a positive correlation between protein and gene expression for ERM/ETV5, but not for RUNX1/AML1. Both proteins were present in the nucleus of the tumor cells, whereas RUNX1/AML1, but not ERM/ETV5, was expressed in 7 out of 12 normal endometrial samples, with its expression being restricted to the cytoplasm of the positive cells. We concluded that there is a higher expression of ERM/ETV5 in early stages of EEC, whereas there seems to be a RUNX1/AML1 translocation from cytoplasm to nucleus in EEC neoplastic transformation.