Employing machine learning and microscopy images of AIB1-stained biopsy material to assess the 5-year survival of patients with colorectal cancer.

Our purpose was to employ microscopy images of amplified in breast cancer 1 (AIB1)-stained biopsy material of patients with colorectal cancer (CRC) to: (a) find statistically significant differences (SSDs) in the texture and color of the epithelial gland tissue, between 5-year survivors and non-survivors after the first diagnosis and (b) employ machine learning (ML) methods for predicting the CRC-patient 5-year survival. We collected biopsy material from 54 patients with diagnosed CRC from the archives of the University Hospital of Patras, Greece. Twenty-six of the patients had survived 5 years after the first diagnosis.

NF-κB2 and RELB offer prognostic information in colorectal cancer and NFKB2 rs7897947 represents a genetic risk factor for disease development.

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family of transcription factors plays an important role in immune responses and cancer development and progression. We have focused on NF-κB2 and RELB of the alternative pathway of NF-κB, which remains largely underexplored in colorectal cancer (CRC). We found that NF-κB2 and RELB protein levels were upregulated in tumour and surrounding stromal tissue compared to distant non-neoplastic tissue (NN) and associated stroma (p<0.

DNA Methylation in Epithelial Ovarian Cancer: Current Data and Future Perspectives.

Ovarian cancer is an aggressive disease, and only a few cases are diagnosed at early stages due to the absence of symptoms. Τhe majority of malignant ovarian tumors (>90%) are of epithelial origin and are subdivided into five histological sub types according to different molecular pathogenesis and clinical behavior. High-grade serous ovarian cancer is the most common subtype (70%).

Differentially Methylated Ultra-Conserved Regions Uc160 and Uc283 in Adenomas and Adenocarcinomas Are Associated with Overall Survival of Colorectal Cancer Patients.

Deregulation of the transcribed ultra-conserved regions (T-UCRs) Uc160, Uc283, and Uc346 has been reported in colorectal cancer (CRC) recently. Here, we investigated promoter methylation of these T-UCRs during the adenoma-carcinoma sequence and their clinical significance in CRC patients. Methylation levels were assessed in CRC, adenomas, infiltrated lymph nodes, and metastatic tissue specimens.

Expression of Immune System-Related Membrane Receptors CD40, RANK, BAFFR and LTβR is Associated with Clinical Outcome of Operated Non-Small-Cell Lung Cancer Patients.

An increasing number of studies implicates the NF-κB (Nuclear Factor of kappa light chain gene enhancer in B cells) alternative pathway in non-small-cell lung cancer (NSCLC). We assessed the clinical significance of CD40 (Tumor necrosis factor receptor superfamily member 5, TNFRSF5), BAFFR (B-cell activating factor receptor), RANK (Receptor activator of NF-κB) and LTβR (lymphotoxin β receptor) receptors, which activate the alternative pathway of NF-κB, in NSCLC. Evaluation of CD40, BAFFR, RANK and LTβR expression was performed based on the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets, while protein expression was assessed by immunohistochemistry in specimens from 119 operated NSCLC patients.

Correlating Changes in the Epithelial Gland Tissue With Advancing Colorectal Cancer Histologic Grade, Using IHC Stained for AIB1 Expression Biopsy Material.

Objective: The objective of this study was to study the textural and color changes occurring in the epithelial gland tissue with advancing colorectal cancer (CRC), utilizing immunohistochemical stain for AIB1 expression biopsy material.

Material And Methods: Clinical material comprised biopsy specimens of 67 patients with a diagnosis of CRC. Two experienced pathologists used H&E-stained material for grading CRC lesions and immunohistochemical (IHC) stain for AIB1 expression.

Evaluation of T-lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin.

Background: Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T-cells (Tregs) in these lesions.

Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas.

Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed.

Neuroendocrine (small-cell) carcinomas: why they teach us essential lessons about prostate cancer.

Atypical clinical features in men with prostate cancer-such as clinical evidence of disease progression in the absence of a proportional increase in serum prostate-specific antigen level, bulky symptomatic tumor masses, exclusive visceral metastases, or a predominance of lytic bone metastases-should alert the clinician that an aggressive prostate cancer variant is present or emerging. Aggressive variants of prostate cancer often take the form of neuroendocrine or small-cell carcinomas, which frequently lack androgen receptor expression and respond poorly to hormonal therapies. Indeed, the finding of neuroendocrine or small-cell prostate carcinoma indicates the need for multimodality treatments that incorporate early combination chemotherapy and locoregional control of bulky tumor deposits, including untreated or recurrent primaries.

Expression of claudins-1, -4, -5, -7 and occludin in hepatocellular carcinoma and their relation with classic clinicopathological features and patients' survival.

Background: Occludin and claudins are integral constituents of tight junction proteins and are de-regulated in various malignancies, including hepatocellular carcinoma (HCC). This study investigated whether expression of claudins 1, 4, 5, 7 and occludin may be used as prognostic markers for overall and disease-free survival in patients with HCC after hepatectomy.

Patients And Methods: The study included 67 hepatectomy specimens obtained from an equal number of patients with HCC who underwent partial hepatectomy at the Patras University Hospital for therapeutic reasons.

Integrative molecular profiling reveals asparagine synthetase is a target in castration-resistant prostate cancer.

The identification of new and effective therapeutic targets for the lethal, castration-resistant stage of prostate cancer (CRPC) has been challenging because of both the paucity of adequate frozen tissues and a lack of integrated molecular analysis. Therefore, in this study, we performed a genome-wide analysis of DNA copy number alterations from 34 unique surgical CRPC specimens and 5 xenografts, with matched transcriptomic profiling of 25 specimens. An integrated analysis of these data revealed that the asparagine synthetase (ASNS) gene showed a gain in copy number and was overexpressed at the transcript level.

Effects of abiraterone acetate on androgen signaling in castrate-resistant prostate cancer in bone.

Purpose: Persistent androgen signaling is implicated in castrate-resistant prostate cancer (CRPC) progression. This study aimed to evaluate androgen signaling in bone marrow-infiltrating cancer and testosterone in blood and bone marrow and to correlate with clinical observations.

Patients And Methods: This was an open-label, observational study of 57 patients with bone-metastatic CRPC who underwent transiliac bone marrow biopsy between October 2007 and March 2010.

Modeling a lethal prostate cancer variant with small-cell carcinoma features.

Purpose: Small-cell prostate carcinoma (SCPC) morphology predicts for a distinct clinical behavior, resistance to androgen ablation, and frequent but short responses to chemotherapy. We sought to develop model systems that reflect human SCPC and can improve our understanding of its biology.

Experimental Design: We developed a set of castration-resistant prostate carcinomas xenografts and examined their fidelity to their human tumors of origin.

Prognostic value of novel biomarkers in astrocytic brain tumors: nuclear receptor co-regulators AIB1, TIF2, and PELP1 are associated with high tumor grade and worse patient prognosis.

Estrogen receptors alpha (ERα) and beta (ERβ) and their co-regulatory proteins are key components of complex signaling networks that specifically regulate the growth and development of various tissues and tumors. Still, their protein expression profiles and possible role in the pathogenesis of astrocytic tumors remain largely unknown. The purpose of the present study is to evaluate the differential protein expression of ΕRα, ERβ, and their co-activators, AIB1, TIF2, and PELP1 in astrocytic tumors of World Health Organization (WHO) grade II-IV, using immunohistochemistry.

Expression of hedgehog pathway components in prostate carcinoma microenvironment: shifting the balance towards autocrine signalling.

Aims: The hedgehog (Hh) signalling pathway has been implicated in the pathogenesis and aggressiveness of prostate cancer through epithelial-mesenchymal interactions. The aim of this study was to elucidate the cell-type partitioned expression of the Hh pathway biomarkers in the non-neoplastic and tumour microenvironments and to correlate it with the grade and stage of prostate cancer.

Methods And Results: Expression of the Hh pathway components (Shh, Smo, Ptch, Gli1) in the microenvironment of non-neoplastic peripheral zone (n = 119), hormone-naive primary prostate carcinoma (n = 141) and castrate-resistant bone marrow metastases (n = 53) was analysed using immunohistochemistry in tissue microarrays and bone marrow sections.

Persistent, biologically meaningful prostate cancer after 1 year of androgen ablation and docetaxel treatment.

Purpose: Clinicians are increasingly willing to treat prostate cancer within the primary site in the presence of regional lymph node or even limited distant metastases. However, no formal study on the merits of this approach has been reported. We used a preoperative clinical discovery platform to prioritize pathways for assessment as therapeutic targets and to test the hypothesis that the primary site harbors potentially lethal tumors after aggressive treatment.

Therapeutic targeting of the prostate cancer microenvironment.

Solid tumors can be thought of as multicellular 'organs' that consist of a variety of cells as well as a scaffold of noncellular matrix. Stromal-epithelial crosstalk is integral to prostate cancer progression and metastasis, and androgen signaling is an important component of this crosstalk at both the primary and metastatic sites. Intratumoral production of androgen is an important mechanism of castration resistance and has been the focus of novel therapeutic approaches with promising results.

High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology.

Background: Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results.

Methods: Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival.

Histologic-type specific role of cell cycle regulators in non-small cell lung carcinoma.

Background: Lung cancer is the most lethal type of cancer in humans. Cell cycle alterations have commonly been encountered in lung cancer and may have prognostic value.

Materials And Methods: This study investigates the immunohistochemical expression of the important cell cycle regulators phosphatase and tensin homolog deleted on chromosome 10 (PTEN), p27, Cks1, and Skp2 in 128 non-small cell lung carcinomas (64 adenocarcinomas, 46 squamous cell carcinomas, and 18 large cell undifferentiated carcinomas) and adjacent non-neoplastic lung tissue.

Expression of ERalpha, ERbeta and co-regulator PELP1/MNAR in colorectal cancer: prognostic significance and clinicopathologic correlations.

Background: Estrogen receptor beta (ERbeta) is abundantly expressed in colorectal tissue, but its role in colorectal carcinogenesis remains elusive. ER novel co-regulator, proline-, glutamic acid- and leucine-rich protein 1 (PELP1/MNAR) has been characterized, but its expression in colorectal carcinomas has not been investigated.

Methods: ERalpha, ERbeta and PELP1/MNAR protein expression were evaluated by immunohistochemistry in colorectal normal mucosa, adenomas and adenocarcinomas from 113 patients with colorectal cancer.

The potential role of Bcl-2 expression, apoptosis and cell proliferation (Ki-67 expression) in cases of gastric carcinoma and correlation with classic prognostic factors and patient outcome.

Background: This study investigated the presence of apoptosis and proliferation in gastric cancer and assesses their possible correlation with classic prognostic markers and patients' survival.

Patients And Methods: The study comprised 110 patients with gastric carcinoma who underwent gastrectomy for therapeutic reasons, and did not receive any pre- or postoperative treatment. Patients were followed up for 3.

Estrogen signaling in colorectal carcinoma microenvironment: expression of ERbeta1, AIB-1, and TIF-2 is upregulated in cancer-associated myofibroblasts and correlates with disease progression.

Epidemiological and molecular data suggest the involvement of estrogen signaling in colorectal tissue, mediated mainly through estrogen receptor beta (ERbeta). Estrogens may mediate their effects in epithelial cells indirectly by acting on stromal cells. Expression of ERalpha, ERbeta1, and the ER coregulators, amplified in breast cancer-1 (AIB-1) and transcriptional intermediary factor 2 (TIF-2), was evaluated in myofibroblasts of 107 colorectal carcinomas, 77 paired samples of normal mucosa, and 29 adenomas by immunohistochemistry.