The Co-Expression of Estrogen Receptors ERα, ERβ, and GPER in Endometrial Cancer.

Estrogens have important roles in endometrial cancer (EC) and exert biological effects through the classical estrogen receptors (ERs) ERα and ERβ, and the G-protein-coupled ER, GPER. So far, the co-expression of these three types of ERs has not been studied in EC. We investigated ERα, ERβ, GPER mRNA and protein levels, and their intracellular protein distributions in EC tissue and in adjacent control endometrial tissue.

AKR1B1 as a Prognostic Biomarker of High-Grade Serous Ovarian Cancer.

Although aldo-keto reductases (AKRs) have been widely studied in cancer, no study to date has examined the roles of AKR family 1 members B1 (AKR1B1) and B10 (AKR1B10) in a large group of ovarian cancer patients. AKR1B1 and AKR1B10 play a significant role in inflammation and the metabolism of different chemotherapeutics as well as cell differentiation, proliferation, and apoptosis. Due to these functions, we examined the potential of AKR1B1 and AKR1B10 as tissue biomarkers.

AKR1B1 and AKR1B10 as Prognostic Biomarkers of Endometrioid Endometrial Carcinomas.

The roles of aldo-keto reductase family 1 member B1 (AKR1B1) and B10 (AKR1B10) in the pathogenesis of many cancers have been widely reported but only briefly studied in endometrial cancer. To clarify the potential of AKR1B1 and AKR1B10 as tissue biomarkers of endometrial cancer, we evaluated the immunohistochemical levels of AKR1B1 and AKR1B10 in tissue paraffin sections from 101 well-characterized patients with endometrioid endometrial cancer and 12 patients with serous endometrial cancer and compared them with the clinicopathological data. Significantly higher immunohistochemical levels of AKR1B1 and AKR1B10 were found in adjacent non-neoplastic endometrial tissue compared to endometrioid endometrial cancer.

Quality Control in the Slovenian National Colorectal Cancer Screening Program.

Objectives: The objective of the study was to assess the impact of an internal quality indicator (QI) audit on the quality level of colonoscopies in the National Colorectal Cancer Screening Program (NCCSP).

Design: Sixty-eight colonoscopists from 29 endoscopic centres participated in the NCCSP from April 2009 to January 2015. Controlled QIs were the percentage of total colonoscopies, adenoma detection rate (ADR), mean adenoma per procedure (MAP), mean adenoma per positive procedure (MAP+), right-sided ADR, sessile serrated lesion (SSL) detection rate, and patient responses to post-procedural questionnaires.

Altered Profile of E1-S Transporters in Endometrial Cancer: Lower Protein Levels of ABCG2 and OSTβ and Up-Regulation of Expression.

Endometrial cancer (EC) is associated with increased estrogen actions. Locally, estrogens can be formed from estrone-sulphate (E1-S) after cellular uptake by organic anion-transporting polypeptides (OATP) or organic anion transporters (OAT). Efflux of E1-S is enabled by ATP Binding Cassette transporters (ABC) and organic solute transporter (OST)αβ.

The impact of 6 years of the National Colorectal Cancer Screening Program on colorectal cancer incidence and 5-year survival.

We aimed to assess the impact of the first three rounds of the National Colorectal Cancer Screening Program (NCCSP) on CRC incidence and mortality in Slovenia. In NCCSP, we use two fecal immune tests (FITs) and if test is positive patient is referred to colonoscopy. From 2009, we invite Slovenian residents aged 50-69 years, one screening round takes 2 years.

AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas.

The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers.

Membrane progesterone receptors β and γ have potential as prognostic biomarkers of endometrial cancer.

Endometrial cancer (EC) is one of the most common malignancies in women worldwide. EC is linked to chronic exposure to estrogens that is unopposed by protective effects of progesterone. Progesterone modulates gene expression via classical nuclear receptors, and has rapid effects via the less characterized membrane-bound progesterone receptors (mPRs) of the progestin and adipoQ receptor (PAQR) family.

Cancer Stem Cell-Related Marker NANOG Expression in Ovarian Serous Tumors: A Clinicopathological Study of 159 Cases.

Objective: The objectives of this study were to assess cancer stem cell-related marker NANOG expression in ovarian serous tumors and to evaluate its prognostic significance in relation to ovarian serous carcinoma.

Methods: NANOG protein expression was immunohistochemically evaluated in the ovarian tissue microarrays of 20 patients with benign ovarian serous tumors, 30 patients with borderline ovarian serous tumors, and 109 patients with ovarian serous carcinomas, from which 106 were of high-grade and 3 of low-grade morphology Immunohistochemical reaction was scored according to signal intensity and the percentage of positive cells in tumor samples. Pursuant to our summation of signal intensity and positive cell occurrence, we divided our samples into 4 groups: NANOG-negative, NANOG-slightly positive, NANOG-moderately positive, and NANOG-strongly positive group.

Novel algorithm including CA-125, HE4 and body mass index in the diagnosis of endometrial cancer.

Objectives: To evaluate the diagnostic and prognostic potential of preoperative serum CA-125 and HE4 levels in patients with endometrial cancer.

Methods: Prospective case-control study of 133 women who underwent surgical treatment at the University Medical Centre Ljubljana (64 patients with endometrial cancer, 69 control patients with prolapsed uterus or myoma). Serum CA-125 and HE4 levels were determined using electrochemiluminescent assays.

The Significance of the Sulfatase Pathway for Local Estrogen Formation in Endometrial Cancer.

Endometrial cancer (EC) is the most common estrogen-dependent gynecological malignancy in the developed World. To investigate the local formation of estradiol (E2), we first measured the concentrations of the steroid precursor androstenedione (A-dione) and the most potent estrogen, E2, and we evaluated the metabolism of A-dione, estrone-sulfate (E1-S), and estrone (E1) in cancerous and adjacent control endometrium. Furthermore, we studied expression of the key genes for estradiol formation via the aromatase and sulfatase pathways.

Data on expression of genes involved in estrogen and progesterone action, inflammation and differentiation according to demographic, histopathological and clinical characteristics of endometrial cancer patients.

Endometrial cancer is the sixth most common cancer in women worldwide. It is associated with aberrant actions of steroid hormones, estrogens and progesterone, but also with enhanced inflammation and reduced cellular differentiation. Here, we show data on demographic and histopathological characteristics of 51 patients with endometrial cancer, together with data on correlations between the expression of 38 genes involved in estrogen and progesterone actions, inflammation and differentiation, and demographic characteristics.

STAR and AKR1B10 are down-regulated in high-grade endometrial cancer.

Endometrial cancer is the most frequent gynecological malignancy in the developed world. The majority of cases are estrogen dependent, and are associated with diminished protective effects of progesterone. Endometrial cancer is also related to enhanced inflammation and decreased differentiation.

Association between polymorphisms in segregation genes BUB1B and TTK and gastric cancer risk.

Background: Malignant transformation of normal gastric cells is a complex and multistep process, resulting in development of heterogeneous tumours. Susceptible genetic background, accumulation of genetic changes, and environmental factors play an important role in gastric carcinogenesis. Single nucleotide polymorphisms (SNPs) in mitotic segregation genes could be responsible for inducing the slow process of accumulation of genetic changes, leading to genome instability.

Results of the FIT-based National Colorectal Cancer Screening Program in Slovenia.

Background: Colorectal cancer (CRC) is one of the most common malignancies in the western world.

Objective: We aimed to assess the first round of fecal immunochemical test (FIT)-based National CRC screening program (NCSP).

Methods: In the NCSP conducted in Slovenia, a FIT and colonoscopy for those tested positive was used.

Two-dimensional gel electrophoresis of gastric tissue in an alkaline pH range.

2DE in combination with MS has facilitated the discovery of several proteins with altered abundance in gastric cancer. While acidic and wide pH ranges have been widely investigated, analysis in the alkaline pH range has not been specifically performed in gastric cancer to date. In the present study, we initially optimized the 2DE in alkaline pH range (pH 7-11) for gastric tissue samples.

Proteomic analysis of gastric cancer and immunoblot validation of potential biomarkers.

Aim: To search for and validate differentially expressed proteins in patients with gastric adenocarcinoma.

Methods: We used two-dimensional gel electrophoresis and mass spectrometry to search for differentially expressed proteins in patients with gastric adenocarcinoma. A set of proteins was validated with immunoblotting.

Angiogenesis in triple-negative adenoid cystic carcinomas of the breast.

We compared microvascular density (MVD), lymph vessel density (LVD), and the expression of hypoxia pathway-associated proteins between primary triple-negative adenoid cystic carcinoma of the breast (TN-ACC) and grade-matched triple-negative breast carcinomas of no special type (TNBC). Twelve TN-ACC and 15 TNBC were investigated immunohistochemically for CD31, podoplanin (D2-40), von Hippel-Lindau protein (pVHL), and hypoxia-inducible factor-1alpha (HIF-1α) protein. All cases were lymph node negative (pN0).

Combined effect of CYP1B1, COMT, GSTP1, and MnSOD genotypes and risk of postmenopausal breast cancer.

Objective: Estrogen plays a key role in breast cancer development and functionally relevant genetic variants within the estrogen metabolic pathway are prime candidates for a possible association with breast cancer risk. We investigated the independent and the combined effects of commonly occurring polymorphisms in four genes encoding key proteins of estrogen metabolic pathway on their potential contribution to breast cancer risk.

Methods: We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women.

Breast tumor characteristics in hormone replacement therapy users.

The aim of this study was to further elucidate the influence of HRT use, regarding duration, regimen and route of administration, on breast tumor characteristics. We evaluated the associations between HRT use and breast tumor characteristics in 530 postmenopausal women diagnosed with invasive breast cancer. Detailed information on HRT use and mammographic attendance were collected through a postal questionnaire.

Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer.

Association between long-term hormone replacement therapy (HRT) use and increased risk of breast cancer is still under debate. Functionally relevant genetic variants within the estrogen metabolic pathway may alter exposure to exogenous sex hormones and affect the risk of postmenopausal breast cancer. We investigated the associations of common polymorphisms in 4 genes encoding key proteins of the estrogen metabolic pathway, duration of HRT use and their interactions with breast cancer risk.

IMP3, a proposed novel basal phenotype marker, is commonly overexpressed in adenoid cystic carcinomas but not in apocrine carcinomas of the breast.

Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) is a member of the insulin-like growth factor-II signaling pathway, and has recently been described as a biomarker of basal-like breast carcinomas. This study explored IMP3 expression in adenoid cystic carcinomas of the breast, a special type of basal-like, triple-negative (estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2/neu protein negative) carcinoma and compared it with a group of apocrine carcinomas, which are an example of estrogen receptor/progesterone receptor negative, special type of breast carcinoma. Eighteen breast adenoid cystic carcinomas (16 primary and 2 corresponding metastases) and 18 apocrine carcinomas (16 invasive and 2 in situ) were evaluated for the expression of IMP3 protein using immunohistochemical method.

ER-α36, a novel isoform of ER-α66, is commonly over-expressed in apocrine and adenoid cystic carcinomas of the breast.

Background: ER-α36 is a novel 36 kDa isoform of the full-length oestrogen receptor alpha (ER-α66). ER-α36 primarily localises to the cytoplasm and the plasma membrane, and responds to membrane-initiated oestrogen and antioestrogen signalling pathways.

Aim: To examine the expression of ER-α36 in apocrine and adenoid cystic carcinoma of the breast, both of which are consistently ER-α66 negative and currently lack effective targeted therapeutic options.

Adenoid cystic carcinomas of the breast have low Topo IIα expression but frequently overexpress EGFR protein without EGFR gene amplification.

Adenoid cystic carcinoma of the breast is a rare subtype of breast cancer with basal-like features. Published studies on breast adenoid cystic carcinoma are limited, resulting in relatively scarce information on the value of predictive tumor markers. We studied 20 primary cases of adenoid cystic carcinoma of the breast for expression of estrogen receptor, progesterone receptor, androgen receptor, epidermal growth factor receptor, HER-2/neu, and topoisomerase IIα using immunohistochemistry and fluorescent in situ hybridization methods.