RUVBL1 in Clear-Cell Renal Cell Carcinoma: Unraveling Prognostic Significance and Correlation with HIF1A.

This study investigates the roles of RUVBL1 and HIF1A in ccRCC development and explores their clinical significance as prognostic biomarkers. mRNA and protein expressions were analyzed using TCGA data and an institutional tissue cohort, respectively. Correlations with clinicopathological parameters and patient outcomes were assessed. TCGA data revealed significantly elevated RUVBL1 mRNA expression in ccRCC tissues, associated with advanced histological grade, T stage, lymph node metastasis, and clinical stage. High RUVBL1 mRNA expression correlated with inferior overall survival and served as an adverse prognostic factor. Similarly, HIF1A mRNA expression was significantly higher in ccRCC tissues, correlating with worse overall survival and acting as an adverse prognostic factor for treatment outcomes. Simultaneous evaluation of RUVBL1 and HIF1A mRNA expression demonstrated enhanced prognostic capacity, surpassing the predictive power of individual markers. Immunohistochemical staining confirmed substantial upregulation of both RUVBL1 and HIF-1α proteins in ccRCC tissues. Furthermore, high expression of both RUVBL1 and HIF-1α proteins was significantly associated with shorter patient survival time. Our findings underscore the significance of RUVBL1 and HIF-1α as potential prognostic markers in ccRCC, paving the way for further research to translate these insights into clinically relevant applications.

Machine learning approach for ambient-light-corrected parameters and the Pupil Reactivity (PuRe) score in smartphone-based pupillometry.

Introduction: The pupillary light reflex (PLR) is the constriction of the pupil in response to light. The PLR in response to a pulse of light follows a complex waveform that can be characterized by several parameters. It is a sensitive marker of acute neurological deterioration, but is also sensitive to the background illumination in the environment in which it is measured. To detect a pathological change in the PLR, it is therefore necessary to separate the contributions of neuro-ophthalmic factors from ambient illumination. Illumination varies over several orders of magnitude and is difficult to control due to diurnal, seasonal, and location variations. Methods and results: We assessed the sensitivity of seven PLR parameters to differences in ambient light, using a smartphone-based pupillometer (AI Pupillometer, Solvemed Inc.). Nine subjects underwent 345 measurements in ambient conditions ranging from complete darkness (<5 lx) to bright lighting (≲10,000 lx). Lighting most strongly affected the initial pupil size, constriction amplitude, and velocity. Nonlinear models were fitted to find the correction function that maximally stabilized PLR parameters across different ambient light levels. Next, we demonstrated that the lighting-corrected parameters still discriminated reactive from unreactive pupils. Ten patients underwent PLR testing in an ophthalmology outpatient clinic setting following the administration of tropicamide eye drops, which rendered the pupils unreactive. The parameters corrected for lighting were combined as predictors in a machine learning model to produce a scalar value, the Pupil Reactivity (PuRe) score, which quantifies Pupil Reactivity on a scale 0-5 (0, non-reactive pupil; 0-3, abnormal/"sluggish" response; 3-5, normal/brisk response). The score discriminated unreactive pupils with 100% accuracy and was stable under changes in ambient illumination across four orders of magnitude. Discussion: This is the first time that a correction method has been proposed to effectively mitigate the confounding influence of ambient light on PLR measurements, which could improve the reliability of pupillometric parameters both in pre-hospital and inpatient care settings. In particular, the PuRe score offers a robust measure of Pupil Reactivity directly applicable to clinical practice. Importantly, the formulae behind the score are openly available for the benefit of the clinical research community.

Recent Research Advances in Double-Strand Break and Mismatch Repair Defects in Prostate Cancer and Potential Clinical Applications.

Prostate cancer remains a leading cause of cancer-related death in men worldwide. Recent research advances have emphasized the critical roles of mismatch repair (MMR) and double-strand break (DSB) in prostate cancer development and progression. Here, we provide a comprehensive review of the molecular mechanisms underlying DSB and MMR defects in prostate cancer, as well as their clinical implications. Furthermore, we discuss the promising therapeutic potential of immune checkpoint inhibitors and PARP inhibitors in targeting these defects, particularly in the context of personalized medicine and further perspectives. Recent clinical trials have demonstrated the efficacy of these novel treatments, including Food and Drugs Association (FDA) drug approvals, offering hope for improved patient outcomes. Overall, this review emphasizes the importance of understanding the interplay between MMR and DSB defects in prostate cancer to develop innovative and effective therapeutic strategies for patients.

Expression differences between proteins responsible for DNA damage repair according to the Gleason grade as a new heterogeneity marker in prostate cancer.

Introduction: The purpose of this research was to explore the correlation between Gleason score and pattern and the expression of the MLH1, MSH2, MDC1, TP53BP1 proteins in prostate cancer (PC). Prostate cancer development is related to errors in DNA, among others double-strand breaks (DSB) and changes in the base sequence of the DNA. These errors should be repaired through mismatch (MMR) or DSB repair proteins such as MSH2, MLH1, MDC1 and TP53BP1. Material and methods: A total of 500 prostate cancer specimens were recruited in this study. From among all gathered specimens the 52 most suitable cases were selected. The expression of examined proteins was detected by immunohistochemistry, and its correlation with the Gleason score and pattern were further analyzed through standard statistical algorithms. Results: The results show a significant correlation between Gleason pattern and the nuclear expression of the MSH2 protein and the cytoplasmic expression of the MLH1 protein. Gleason score significantly correlates with the nuclear and the cytoplasmic expression of the MSH2 protein and the cytoplasmic expression of the MDC1 protein. There is no correlation between the nuclear or cytoplasmic expression of the TP53BP1 protein and Gleason pattern or score. Conclusions: Our study suggests that the aberration in the MMR repair mechanism may be significantly more important regarding the grading among PC cells in comparison to the impact of alterations in the DSB repair mechanism. The lack of correlation between expression of the TP53BP1 protein and Gleason pattern and Gleason score suggests that the radiation resistance of PC is independent of alterations connected with TP53BP1.

Cationic nanoemulsion vs. 0.15% sodium hyaluronate artificial tears in the healing process following modern surface keratorefractive surgery.

PURPOSE: The aim of this study was to investigate the influence of artificial tears containing either cationic nanoemulsion (CCN) or sodium hyaluronate artificial tears (SH) on early postoperative healing after modern surface refractive surgery. MATERIALS AND METHODS: In this multicenter, prospective, double-masked, parallel-group (1:1), comparative study, 129 patients (n = 255 eyes) were randomized to receive CCN (n = 128) or SH (n = 127) as an adjuvant treatment after either transepithelial photorefractive keratectomy (transPRK) or Epi-Bowman keratectomy (EBK). The patients' perspectives were gathered using the Ocular Surface Disease Index (OSDI) questionnaire, and uncorrected (UCVA), and corrected (BCVA) visual acuity were assessed before and one week and one month after the procedure. In addition, corneal epithelization and subjective assessment of visual blur and eye irritation on drop instillation were assessed at one week postoperatively. RESULTS: No statistically significant differences were found between two groups in age, spherical equivalent refractive error, UCVA, BCVA or OSDI scores before the procedure. There was also no difference between groups in UCVA one week and one month after the procedure. However, statistically significantly lower OSDI scores were found one week and one month after the procedure in the CCN group. Moreover, blurred vision after use of the eye drops was observed less frequently in the CCN group than in the SH group. CONCLUSIONS: The CCN and SH groups had similar postoperative UCVA. However the significantly lower OSDI scores and less frequently blurred vision after application of the eye drops in the CCN group suggest better subjective outcomes in this group.

Vascular density and macular sensitivity in eyes after scleral buckling surgery for macula-on rhegmatogenous retinal detachment.

PURPOSE: To investigate the structure and function of the retina after scleral buckling (SB) surgery due to macula-on rhegmatogenous retinal detachment (RRD). METHODS: Twenty eyes with repaired macula-on RRD and 20 fellow eyes were included. All patients within 6-12 months of the procedure, were examined to evaluate retinal structure using spectral domain optical coherence tomography (SD-OCT) and vessel density (VD) by OCT angiography (OCTA). Best corrected visual acuity (BCVA) and microperimetry (MP) tests were used to assess retinal function. RESULTS: Analysis of the microvascular network using OCTA between the operated and healthy fellow eyes showed a significant reduction on VD in superficial vascular plexus (SVP), deep vascular plexus (DVP) and radial peripapillary capillaries (RPC) (p< 0.001, p = 0.019 and p = 0.008, respectively). Comparison of retinal structure in SD-OCT showed no significant differences on thickness in ganglion cell complex (GCC) and peripaillary retinal nerve fiber layer (pRNFL) (p> 0.05) between examined eyes. Retinal function analysis by MP examination showed a decrease of retinal sensitivity (p = 0.0013) whereas postoperative BCVA showed no differences (p = 0.62) in the operated eyes. Significant Pearson's correlations were observed between retinal sensitivity and VD in SVP, RPC (p< 0.05). CONCLUSION: In the eyes after SB surgery due to macula-on RRD, changes in retinal sensitivity were accompanied by impairment of the microvascular network assessed by the OCTA.

The Prognostic Role of ACO2 in Renal Cell Carcinoma.

BACKGROUND/AIM: Renal cell carcinoma (RCC) continues to pose a challenge due to our limited understanding of its underlying pathophysiology. Aconitase 2 (ACO2) is a mitochondrial Fe-S cluster enzyme that catalyzes the stereospecific isomerization of citrate to isocitrate in the second step of the Krebs cycle. We investigated the relationship between ACO2 protein expression and the clinical course of RCC. MATERIALS AND METHODS: Tumor samples were evaluated in a commercial tissue microarray for ACO2 expression using the H-score. The tissue microarrays contained a total of 96 cores from primary tumors, matched metastases, and matched adjacent tissues derived from 32 patients with RCC. The mean follow-up was 82.74 months. Correlation analysis of clinicopathological data and survival was performed. Expression levels of ACO2 mRNA were compared using publicly available data. RESULTS: All the tissue samples showed cytoplasmic ACO2 expression, with median H-scores of 139.7, 130.3 and 166.7 in primary tumor, metastatic tissue, and matched control tissue, respectively. A significantly higher ACO2 expression was found in normal tissues compared to primary and metastatic RCC. The analysis demonstrated a significantly positive correlation between ACO2 expression in primary tumors and their metastases. The results also showed a significant correlation between the expression of ACO2 and worse overall survival among patients with RCC. CONCLUSION: ACO2 may be used as a prognostic factor in RCC. Significant alterations in ACO2 expression are thought to occur in the early stages of RCC carcinogenesis. Considering the physiological role of ACO2, its dysregulation may constitute an adaptive trait of RCC for escaping the equilibrium phase of immunoediting.

TOLLIP Protein Expression Predicts Unfavorable Outcome in Renal Cell Carcinoma.

Resistance to systemic therapy is one of the hallmarks of renal cell carcinoma (RCC). Recently, TOLLIP has emerged as a possible driver of autophagy and chemoresistance. We explored the relationship between primary and metastatic RCC tumor characteristics, patient survival, and TOLLIP expression. The tissue microarrays cohort contained 95 cores of the primary tumor, matched metastases, and matched adjacent tissues derived from 32 RCC patients. TOLLIP expression in tumor samples was evaluated using the H-score. All examined samples showed cytoplasmic TOLLIP expression, with a median value of 100 in primary tumors, 107.5 in metastases, and 220 in the control group. The expression was significantly higher in the normal adjacent tissues compared to primary or metastatic RCC (p < 0.05). We found a positive correlation between expressions of TOLLIP in the primary tumor and its metastases (p < 0.05; k = 0.48). TOLLIP expression significantly correlates with a lower overall survival rate (p = 0.047). TOLLIP functions as a ubiquitin-LC3 adaptor in the intracellular pathway associated with autophagy. Relative TOLLIP overexpression may augment autophagy-related signaling, limiting susceptibility to therapy. The blockade of TOLLIP physiological function seems to be a promising approach to overcoming resistance to systemic therapy.

Overexpression of kif11 is a poor prognostic factor in clear cell renal cell carcinoma.

INTRODUCTION: Unresectable renal cell carcinoma continues to be a great challenge due to our limited understanding of its underlying pathophysiology. We explored the relationship between KIF11 protein expression and the clinical courses of clear cell renal cell carcinoma (ccRCC) using a tissue microarray. MATERIAL AND METHODS: The tissue microarray contained specimens derived from 90 patients, cancer and matched adjacent non-cancerous tissue (2 cores per case), followed up for 7 years. Tumour samples were evaluated for KIF11 expression using the H-score, and their correlations with clinicopathological data and survival data were analysed. RESULTS: 72.7% of ccRCC tissues presented KIF11 cytoplasmic expression with a median value of 20 (interquartile range 0-200). The nuclear staining was positive in 36.36% of ccRCC tissues. Among controls, nuclear KIF11 expression was absent, but cytoplasmic expression was identified in all cases, with a median value of 230 (interquartile range 45-290). Cytoplasmic KIF11 expression in ccRCC tissues was lower than in the control tissues and was positively correlated with tumour grade and mortality (p < 0.05). KIF11 nuclear expression did not correlate with overall survival. CONCLUSIONS: Elevated expression of KIF11 predicts poor clinical outcome in ccRCC patients. Downregulation of KIF11 may provide a new therapeutic strategy for ccRCC.

Intraretinal Cysts as a Manifestation of Retinal Angiomatous Proliferation in Optical Coherence Tomography Angiography.

Background and Objectives: Intraretinal cysts are common pathology observed inspectral domain optical coherence tomography (SDOCT) in patients with neovascular form of age-related macular degeneration (AMD). The aim of the study was to determine if the presence of intraretinal cysts is positively correlated with diagnosis of retinal angiomatous proliferation (RAP) in optical coherence tomography angiography (OCTA). Material and Methods: A total of 21 eyes with intraretinal cysts in SDOCT exam (Group1) and 21 eyes with subretinal fluid(Group 2) were enrolled into the study. In each eye, the presence of intraretinal neovascularization (IRN) and chorioretinal anastomosis (CRA) was evaluated in OCTA by two experienced graders. Results: IRN was observed in 20 eyes (95.2%) from Group 1 and 5 eyes (23.8%) from Group 2. Features of CRA were found in 18 eyes (80.95%) and 16 eyes (76.2%) respectively for Group 1 and 2. Patients with cysts are 50 (95% CI: 5.43−460.52) times more likely to have IRN (p < 0.001). Conclusions: The presence of intraretinal cysts on SDOCT retinal sections in eyes with neovascular AMD corresponds to the presence of IRN on OCTA examination. The results indicate that the absence of a cyst does not exclude the presence of IRN and CRA which can be identified on OCTA.

Alterations in Fixation Indices in Primary Open-Angle Glaucoma by Microperimetry.

The aim of this study was to determine whether primary open-angle glaucoma (POAG) is associated with changes in fixation stability parameters assessed by microperimetry (MP) and whether the severity of glaucoma is related to a deterioration in these indicators. This study analyzed fixation stability using MP macular analyzer integrity assessment (MAIA) in patients with mild and moderate/severe POAG and healthy controls. The resulting fixation indices were correlated with parameters used to assess retinal function with MP and standard automated perimetry (SAP) and retinal structure with optical coherence tomography (OCT) and OCT angiography (OCTA). We enrolled 54 eyes in the POAG groups (32 eyes with mild POAG and 22 eyes with moderate/severe POAG) and 24 eyes in the healthy group. It was shown that fixation stability in POAG eyes deteriorated with increasing disease severity, and significant differences in bivariate contour ellipse area (BCEA) including 95% of fixation points were observed among groups (p = 0.042). Quantitative analysis of structural and functional retinal parameters also showed significant deterioration with the progression of glaucoma (p < 0.001). Correlations among fixation parameters and abnormalities in the retinal structure and function were confirmed. We concluded that POAG is associated with disturbances in the fixation pattern, which worsen as the disease progresses and can be effectively assessed by performing a MP test.

The clinical, prognostic and therapeutic significance of liver cancer stem cells and their markers.

Hepatocellular carcinoma (HCC) is the fourth most common cause of death among cancers. The poor prognosis of HCC might be caused by a population of cancer stem cells (CSC). CSC have similar characteristics to normal stem cells and are responsible for cancer recurrence, chemoresistance, radioresistance and metastasis. Liver cancer stem cells (LCSC) are identified via specific surface markers, such as CD44, CD90, CD133, and EpCAM (CD326). Recent studies suggested a complex interaction between mentioned LCSC markers and clinical features of HCC. A high expression of CSC is correlated with a negative prognostic factor after surgical resection of HCC and is connected with more aggressive tumor behavior. Moreover, LCSC might be responsible for increasing resistance to sorafenib, a kinase inhibitor drug. A reduction in the LCSC population may be crucial to successful advanced HCC therapy.

Quantitative assessment of retinal thickness and vessel density using optical coherence tomography angiography in patients with Alzheimer's disease and glaucoma.

PURPOSE: Assessment and a direct comparison of retinal vessel density with the thickness of inner retinal layer (IRL) and outer retinal layer (ORL) in the same regions of the macula in subjects with Alzheimer's disease (AD) and primary open-angle glaucoma (POAG). METHODS: We analyzed data from 48 eyes of healthy control (HC) participants, 71 eyes with POAG, and 49 eyes of AD patients. Ophthalmic examination included optical coherence tomography (OCT) imaging to measure IRL and ORL thickness and OCT angiography (OCTA) in the same region for the imaging of vessel density in the superficial vascular plexus (SVP) and deep vascular plexus (DVP) of the retina. A direct comparison of vessel density and retinal layers thickness, which different dynamic ranges, was obtained by normalizing values as percentage losses. RESULTS: Patients with AD presented significantly greater losses of vascular density in the DVP and ORL thickness compared to POAG (p <0.001), but percentage losses of vessel density in SVP and IRL thickness were considerable in POAG compared to AD eyes (p<0.001). Positive associations among presence of AD were observed primarily in outer retina where a 1% decrease of ORL thickness was associated with about 24-29% increase in odds of the presence of AD. According to OCTA measurements, a 1% decrease of vessel density in DVP was positively associated with a 4-9% increase in odds of the presence of AD. In POAG positive associations among presence of disease were observed only in inner retina where 1% loss of IRL thickness and a 1% loss of vessel density in the SVP were positively associated with a 13-23% increase in risk of presence of the disease. CONCLUSIONS: Analysis of ORL thickness and vessel density in DVP could potentially improve diagnostic capabilities and may provide a valuable approach for predicting of AD.

MACULAR SENSITIVITY IN THE AREA OF INTERNAL LIMITING MEMBRANE PEELING IN EYES AFTER PARS PLANA VITRECTOMY WITH THE TEMPORAL INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR A FULL-THICKNESS MACULAR HOLE.

PURPOSE: To examine the relationship between retinal sensitivity and the area of internal limiting membrane (ILM) peeling during pars plana vitrectomy for a full-thickness macular hole. METHODS: Twenty-four eyes a minimum of 6 months after temporal inverted flap pars plana vitrectomy for a full-thickness macular hole were included in the study. En face spectral-domain optical coherence tomography images were used to assess margins of the peeled ILM area. Microperimetry was performed to examine retinal sensitivity within the central 10°. Areas of peeled ILM in en face optical coherence tomography images were correlated with the average sensitivity threshold. Retinal sensitivities at the location of each measurement point were compared with structural abnormalities observed in en face spectral-domain optical coherence tomography images. RESULTS: The mean retinal sensitivity in the area of ILM removal was significantly lower compared with the area of preserved ILM (24.29 ± 3.96 dB vs. 26.19 ± 2.10 dB, P < 0.0001, respectively). The peeled ILM area showed a negative correlation with the average sensitivity threshold (r = -0.56, P < 0.01). CONCLUSION: A larger area of ILM peeling during temporal inverted flap pars plana vitrectomy for a full-thickness macular hole is related to lower retinal sensitivity in the central macula.

TRIP13 predicts poor prognosis in clear cell renal cell carcinoma.

What is the leading molecular mechanism that causes broad resistance to systemic therapies remains a key question in renal cancer related research. We explored associations of TRIP13 expression with the clinical course using the tissue microarray (TMA). The TMA contained specimens from 87 patients diagnosed with clear cell renal cell carcinoma (ccRCC). We performed immunohistochemistry to investigate TRIP13 protein expression levels. The overall survival (OS) was analyzed using the Kaplan-Meier method and log-rank statistics. Univariate and multivariate analyses were conducted using Cox proportional hazard models. Median follow up for the TMA cohort was 7.0 years. Tissues from 28.74% of patients demonstrated high TRIP13 expression. Mean TRIP13 expression in TRIP13-rich tumors was significantly higher comparing to adjacent normal tissues (P < 0.05). TRIP13 expression did not significantly correlate with stage nor tumor grade (P > 0.05). Elevated expression of TRIP13 served as an independent unfavorable prognostic indicator of survival in ccRCC (P < 0.05). TRIP13 overexpression predicts poor prognosis in ccRCC. Together with the emerging reports, this observation raises a suspicion that TRIP13 is a substantial driver of resistance to systemic therapies against kidney cancer.

The prognostic value of leucine-rich repeat-containing G-protein (Lgr5) and its impact on clinicopathological features of colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) constitutes one of the most prevalent malignancies in the world. Recent research suggests that cancer stem cells (CSCs) are responsible for tumor cell's malignant behavior in CRC. This study has been designed to determinate clinical implications of CSC markers: CD44, DCLK1, Lgr5, and ANXA2 in CRC. MATERIALS AND METHODS: The study was performed on tissue samples which were collected from 89 patients undergoing colectomy. Formalin-fixed paraffin-embedded tissue blocks with representative tumor areas were identified and corded. Immunohistochemical staining was performed using anti-CD44, anti-LGR5, anti-ANXA2, and anti-DCLK1 antibodies. The H-score system was utilized to determine the immunointensity of CRC cells. RESULTS: The lower expression of Lgr5 was significantly correlated with the presence of lymph-node metastases (p = 0.011), while high expression of Lgr5 was statistically significant in vascular invasion in examined cancer tissue samples (p = 0.027). Moreover, a high H-score value of Lgr5 expression was significantly related to a reduced overall survival rate (p = 0.043). CONCLUSION: Our results suggest a strong relationship between CSC marker Lgr5 and vascular invasion, presence of lymph-node metastasis, and overall poor survival. The presence of Lgr5 might be an unfavorable prognostic factor, and its high level in cancer tissue is related to an aggressive course. This marker could also be used to access the effectiveness of the treatment.

Correlation of retinal sensitivity in microperimetry with vascular density in optical coherence tomography angiography in primary open-angle glaucoma.

PURPOSE: To evaluate the correlation between retinal sensitivity in microperimetry (MP) with vessel density (VD) using optical coherence tomography angiography (OCTA) in primary open-angle glaucoma (POAG). METHODS: We enrolled 30 participants (52 eyes) with POAG and 15 participants (23 eyes) in the healthy control group. All participants were examined for retinal structure using OCTA to assess VD and Spectral domain OCT (SD-OCT) to assess ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) thickness. Retinal sensitivity was tested with MP and standard automatic perimetry (SAP). RESULTS: The VD in moderate/severe POAG was lower than that in mild POAG and healthy control in the macular superficial vascular plexus (SVP) (38.7±6.3% vs. 42.9±5.2%, 49.7±2.6% respectively, P<0.001) and peripapillary radial peripapillary capillaries (pRPC) (36.4±5.7% vs. 43.6±6.6%, 49.1±2.4% respectively, P<0.001). The Pearson's correlations between function-structure parameters were strongest with MP average sensitivity threshold and SVP VD in the area of whole macula (r = 0.68); followed by SAP mean deviation (MD) and pRNFL thickness (r = 0.63); SAP MD and pRPC VD (r = 0.59) and MP average threshold and GCC thickness (r = 0.54). We found the AUROCs for discriminating between glaucomatous and healthy eyes were highest for structural parameters as follows: pRNFL (0.94), macular SVP whole (0.92), pRPC (0.92) and GCC (0.91). Pairwise comparison of the above parameters showed no difference (P>0.05). CONCLUSION: The relationship between microvascular damage in the macular SVP whole and the decrease of MP average sensitivity threshold is stronger than the pRNFL thickness measurements and SAP parameters. OCTA and MP techniques are valuable methods that allow clinically monitor structural and functional changes in glaucomatous eyes.

The impact of TP53BP1 and MLH1 on metastatic capability in cases of locally advanced prostate cancer and their usefulness in clinical practice.

BACKGROUND: Lymph node (LN) metastases increase the risk of death from prostate cancer (CaP). The dysfunction of factors responsible for DNA injury detection may promote the evolution of localized primary tumors into the metastatic form. METHODS: In this study, 52 cases of CaP were analyzed. The cases were divided into groups of CaP without metastases (N0), with metastases to the LNs (N+), and metastatic LN tissue. Immunohistochemical examinations were performed with antibodies against MDC1, TP53BP1, MLH1, MSH2, MSH6, and PMS2. RESULTS: Statistical analysis showed lower nuclear expression of TP53BP1 in N+ cases than in N0 cases (P = 0.026). Nuclear TP53BP1 expression was lower in LN cases than in N+ cases (P = 0.019). Statistical analysis showed lower nuclear expression of MLH1 in N+ cases than in to N0 cases (P = 0.003). CONCLUSION: Decreased expression of both MLH1 and TP53B1 were demonstrated in N+ cases of CaP. This observation could help to determine the risk of nodal metastasis, and to select appropriate treatment modalities for patients with locally advanced CaP.

The Essential Role of DCLK1 in Pathogenesis, Diagnostic Procedures and Prognostic Stratification of Colorectal Cancer.

Colorectal cancer (CRC) is the second most prevalent type of cancer among males and the third among females. CRC recurrence and poor prognosis may be related to the prevalence of chemotherapy-resistant cancer stem cells (CSCs). Recent studies have indicated the role of doublecortin-like kinase 1 (DCLK1) protein as a marker of CSC in CRC. This review focuses on the role of DCLK1 in CRC. Long-lived DCLK1-positive tuft cells can function as cancer-initiating cells. Numerous studies have shown DCLK1 overexpression to be significantly correlated with the stage of disease, the presence of metastasis and poor survival rate. DCLK1 may also be used to identify patients at high risk and those with chemotherapy-resistant tumors. DCLK1-specific drugs are examined as potential cancer treatments.

Diagnostic difficulties in cases of papillary urothelial neoplasm of low malignant potential, urothelial proliferation of uncertain malignant potential, urothelial dysplasia and urothelial papilloma: A review of current literature.

Tumours of the urinary tract are the fifth most frequent type of cancer. The most common types are urothelial tumours, among which, non-invasive urothelial neoplasms represent 45% of all cases. The 2016 WHO classification of urinary tract tumours introduced new classifications of non-invasive lesions. Besides urothelial papilloma (UP) and papillary urothelial neoplasm of low malignant potential (PUNLMP), as described in the former classification, the new classification also includes new entities such as urothelial proliferation of uncertain malignant potential (UPUMP) and urothelial dysplasia (UD). Of the aforementioned, UPUMP is the lesion that most commonly progresses, but solely to non-invasive carcinomas. UD is associated with a high risk of progression to invasive carcinoma. Understanding the biological character, and establishing the correct differential diagnosis in cases of non-invasive, non-cancerous lesions of the urinary bladder, will be of importance in establishing outcome predictions for future patients. A systematic review of the current literature allows us to systematize genetic, morphologic and prognostic factors of such lesions. Moreover, the collected data provide the basis for a proposed diagnostic algorithm which facilitates quick and effective differential diagnoses in cases of non-invasive non-cancerous urinary bladder lesions.