Altered TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR Predict Shorter Survival in Penile Squamous Cell Carcinoma.

Penile squamous cell carcinoma (pSCC) represents an uncommon malignancy characterized by stagnant mortality, psychosexual distress, and a highly variable prognosis. Currently, the WHO distinguishes between human papillomavirus (HPV) related and HPV independent pSCC. Recently, there has been an evolving line of research documenting the enrichment of HPV-independent pSCC with a high tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) expression, as well as clusters of genes associated with HPV status.

Unraveling the Molecular Landscape of Uterine Tumor Resembling Ovarian Sex Cord Tumor: Insights From A Clinicopathological, Morphologic, Immunohistochemical, and Molecular Analysis of 35 Cases.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor of uncertain lineage and low malignant potential. Most tumors behave in a benign manner, but a subset of UTROSCT exhibit an aggressive clinical course with recurrences and metastases. The recurrent molecular alterations in UTROSCT mostly represent gene fusions involving NCOA1-3.

Somatic Genomic and Transcriptomic Characterization of Primary Ovarian Serous Borderline Tumors and Low-Grade Serous Carcinomas.

Low-grade serous carcinoma (LGSC) may develop from serous borderline tumor (SBT) tissue, where the micropapillary type (mSBT) presents the highest risk for progression. The sensitivity of LGSC to standard chemotherapy is limited, so alternative therapeutic approaches, including targeted treatment, are needed. However, knowledge about the molecular landscape of LGSC and mSBT is limited.

HER2 status as a potential predictive biomarker for ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian carcinoma characterized by unique biological features and highly malignant characteristics including low chemosensitivity. Therefore, new therapeutic targets are needed. These could include the downstream pathways of receptor tyrosine kinases, especially the human epidermal growth factor receptor 2 (HER2).

A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations.

Background: Molecular aberrations occurring in primary ovarian clear cell carcinoma (OCCC) can be of diagnostic, predictive, and prognostic significance. However, a complex molecular study including genomic and transcriptomic analysis of large number of OCCC has been lacking.

Methods: 113 pathologically confirmed primary OCCCs were analyzed using capture DNA NGS (100 cases; 727 solid cancer related genes) and RNA-Seq (105 cases; 147 genes) in order to describe spectra and frequency of genomic and transcriptomic alterations, as well as their prognostic and predictive significance.

Microsatellite instability in non-endometrioid ovarian epithelial tumors: a study of 400 cases comparing immunohistochemistry, PCR, and NGS based testing with mutation status of MMR genes.

Testing of microsatellite instability is not only used as a triage for possible Lynch syndrome, but also to predict immunotherapy treatment response. The aim of this study was to assess the frequency of mismatch repair deficiency (MMR-D)/microsatellite instability (MSI) in 400 cases of non-endometrioid ovarian tumors (high-grade serous, low-grade serous, mucinous and clear cell), to compare different methodological approaches of testing, and to assess the optimal approach for next generation sequencing (NGS) MSI testing. For all tumors, we evaluated immunohistochemical (IHC) expression of MMR proteins and assessed microsatellite markers by PCR-based method.

Comprehensive quantitative analysis of alternative splicing variants reveals the HNF1B mRNA splicing pattern in various tumour and non-tumour tissues.

Hepatocyte nuclear factor-1-beta (HNF1B) is a transcription factor and putative biomarker of solid tumours. Recently, we have revealed a variety of HNF1B mRNA alternative splicing variants (ASVs) with unknown, but potentially regulatory, functions. The aim of our work was to quantify the most common variants and compare their expression in tumour and non-tumour tissues of the large intestine, prostate, and kidney.

Uterine cellular leiomyomas are characterized by common HMGA2 aberrations, followed by chromosome 1p deletion and MED12 mutation: morphological, molecular, and immunohistochemical study of 52 cases.

Cellular leiomyoma (CL) represents an uncommon variant of uterine leiomyoma with limited data concerning its immunohistochemical and molecular profile. We performed a comprehensive analysis of 52 CL cases all of which were analyzed immunohistochemically. Molecular analysis was possible in 32 cases with sufficient DNA, and 38 cases with sufficient RNA.

A comprehensive analysis of the expression, epigenetic and genetic changes of HNF1B and ECI2 in 122 cases of high-grade serous ovarian carcinoma.

High-grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer, with a poor prognosis; however, most studies concerning ovarian carcinoma have focused mainly on clear cell carcinoma. The involvement of hepatocyte nuclear factor 1β (HNF1B) in the carcinogenesis of HGSC has not yet been fully elucidated. To the best of our knowledge, the present study is the first to analyse the expression of the possible downstream target of HNF1B, enoyl-CoA (Δ) isomerase 2 (ECI2), in HGSC.

Analysis of expression, epigenetic, and genetic changes of HNF1B in 130 kidney tumours.

Hepatocyte nuclear factor 1 beta (HNF1B) is a transcription factor which plays a crucial role in nephronogenesis, and its germline mutations have been associated with kidney developmental disorders. However, the effects of HNF1B somatic exonic mutations and its role in the pathogenesis of kidney tumours has not yet been elucidated. Depending on the type of the tumour HNF1B may act as a tumour suppressor or oncogene, although the exact mechanism by which HNF1B participates in the process of cancerogenesis is unknown.

HNF1B, EZH2 and ECI2 in prostate carcinoma. Molecular, immunohistochemical and clinico-pathological study.

Hepatocyte nuclear factor 1 beta (HNF1B) is a tissue specific transcription factor, which seems to play an important role in the carcinogenesis of several tumors. In our study we focused on analyzing HNF1B in prostate carcinoma (PC) and adenomyomatous hyperplasia (AH), as well as its possible relation to the upstream gene EZH2 and downstream gene ECI2. The results of our study showed that on an immunohistochemical level, the expression of HNF1B was low in PC, did not differ between PC and AH, and did not correlate with any clinical outcomes.

Expression, Epigenetic, and Genetic Changes of HNF1B in Colorectal Lesions: an Analysis of 145 Cases.

Hepatocyte nuclear factor 1 beta (HNF1B) is transcription factor which plays a crucial role in the regulation of the development of several organs, but also seems to be implicated in the development of certain tumours, especially the subset of clear cell carcinomas of the ovary and kidney. Depending on the type of the tumour, HNF1B may act as either a tumour suppressor or an oncogene, although the exact mechanism by which HNF1B participates in the process of cancerogenesis is unknown. Using immunohistochemical approach and methylation and mutation analysis, we have investigated the expression, epigenetic, and genetic changes of HNF1B on 40 cases of colorectal adenomas and 105 cases of colorectal carcinomas.

Identification of novel HNF1B mRNA splicing variants and their qualitative and semi-quantitative profile in selected healthy and tumour tissues.

Hepatocyte nuclear factor-1-beta (HNF1B) is a transcription factor crucial for the development of several tissues, and a promising biomarker of certain solid tumours. Thus far, two HNF1B alternative splicing variants (ASVs) have been described, however, the complete spectrum, prevalence and role of HNF1B ASVs in tumorigenesis are unclear. Considering the equivocal data about HNF1B ASVs and expression presented in literature, our aim was to characterize the spectrum of HNF1B mRNA splicing variants across different tissues.

A comprehensive evaluation of pathogenic mutations in primary cutaneous melanomas, including the identification of novel loss-of-function variants.

The most common histological subtypes of cutaneous melanoma include superficial spreading and nodular melanoma. However, the spectrum of somatic mutations developed in those lesions and all potential druggable targets have not yet been fully elucidated. We present the results of a sequence capture NGS analysis of 114 primary nodular and superficial spreading melanomas identifying driver mutations using biostatistical, immunohistochemical and/or functional approach.

The hidden function of egg white antimicrobials: egg weight-dependent effects of avidin on avian embryo survival and hatchling phenotype.

Avidin is a key egg white antimicrobial protein with strong binding capacity for biotin, an essential growth and immune cell precursor. As such, it is assumed to have a pronounced, though still poorly explored, effect on hatchling phenotype. We tested the effect of experimentally increased egg white avidin concentration (AVIDIN+) on hatching success, chick morphology, post-hatching growth performance and innate immune function in a model bird, Japanese quail ().

Effects of experimentally increased in ovo lysozyme on egg hatchability, chicks complement activity, and phenotype in a precocial bird.

In birds, spectrum of egg white proteins deposited into the egg during its formation are thought to be essential maternal effects. Particularly, egg white lysozyme (LSM), exhibiting great between and within species variability, is considered to be essential for developing avian embryos due to its physiological, antimicrobial, and innate immune defense functions. However, there have been few studies investigating effects of LSM on early post-hatching phenotype, despite its broad physiological and protective role during embryogenesis.