Association of Membranous WNT-1 and Nuclear mTOR with Endometrial Cancer Grade.

Endometrial cancer remains a common cancer affecting the female reproductive system. There is still a need for more efficient ways of determining the degree of malignancy and optimizing treatment. WNT and mTOR are components of signaling pathways within tumor cells, and dysfunction of either protein is associated with the pathogenesis of neoplasms. Therefore, the aim of our study was to assess the impact of subcellular WNT-1 and mTOR levels on the clinical course of endometrial cancer. WNT-1 and mTOR levels in the plasma membrane, nucleus, and cytoplasm were evaluated using immunohistochemical staining in a group of 64 patients with endometrial cancer of grades 1-3 and FIGO stages I-IV. We discovered that the levels of WNT-1 and mTOR expression in the cellular compartments were associated with tumor grade and staging. Membranous WNT-1 was negatively associated, whereas cytoplasmic WNT-1 and nuclear mTOR were positively associated with higher grading of endometrial cancer. Furthermore, nuclear mTOR was positively associated with FIGO stages IB-IV. To conclude, we found that the assessment of WNT-1 in the cell membrane may be useful for exclusion of grade 3 neoplasms, whereas cytoplasmic WNT-1 and nuclear mTOR may be used as indicators for confirmation of grade 3 neoplasms.

Current Pathology Model of Pancreatic Cancer.

Pancreatic cancer (PC) is one of the most aggressive and lethal malignant neoplasms, ranking in seventh place in the world in terms of the incidence of death, with overall 5-year survival rates still below 10%. The knowledge about PC pathomechanisms is rapidly expanding. Daily reports reveal new aspects of tumor biology, including its molecular and morphological heterogeneity, explain complicated "cross-talk" that happens between the cancer cells and tumor stroma, or the nature of the PC-associated neural remodeling (PANR). Staying up-to-date is hard and crucial at the same time. In this review, we are focusing on a comprehensive summary of PC aspects that are important in pathologic reporting, impact patients' outcomes, and bring meaningful information for clinicians. Finally, we show promising new trends in diagnostic technologies that might bring a difference in PC early diagnosis.

Comprehensive cancer-oriented biobanking resource of human samples for studies of post-zygotic genetic variation involved in cancer predisposition.

The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.

CD133 Expression in the Nucleus Is Associated with Endometrial Carcinoma Staging and Tumor Angioinvasion.

BACKGROUND: (1) Endometrial cancer is one of the most common cancers affecting women, with a growing incidence. To better understand the different behaviors associated with endometrial cancer, it is necessary to understand the changes that occur at a molecular level. CD133 is one of the factors that regulate tumor progression, which is primarily known as the transmembrane glycoprotein associated with tumor progression or cancer stem cells. The aim of our study was to assess the impact of subcellular CD133 expression on the clinical course of endometrial cancer. (2) Methods: CD133 expression in the plasma membrane, nucleus, and cytoplasm was assessed by immunohistochemical staining in a group of 64 patients with endometrial cancer representing FIGO I-IV stages, grades 1-3 and accounting for tumor angioinvasion. (3) Results: Nuclear localization of CD133 expression was increased in FIGO IB-IV stages compared to FIGO IA. Furthermore, CD133 expression in the nucleus and plasma membrane is positively and negatively associated with a higher grade of endometrial cancer and angioinvasion, respectively. (4) Conclusions: Our findings suggest that positive nuclear CD133 expression in the tumor may be related to a less favorable prognosis of endometrial carcinoma patients and has emerged as a useful biomarker of a high-risk group.

Immunonutrition Changes Inflammatory Response in Colorectal Cancer: Results from a Pilot Randomized Clinical Trial.

INTRODUCTION: Surgery is the first choice of treatment for colorectal cancer. Nutritional support in the form of oral nutritional supplements (ONSs) in the preoperative period is widely accepted for reducing the incidence of perioperative complications, and immunonutrition is generally recommended. However, there is little clinical data regarding the impact of such treatment on tumor biology. MATERIAL AND METHODS: In this study, tumor tissue and blood samples were collected from 26 patients during preoperative colonoscopy at the time of clinical diagnosis (sample A). Group 1 received standard ONSs (3× Nutricia Nutridrink Protein per day) for 2 weeks before surgery. In group 2, immune ONSs (2× Nestle Impact Oral) were administered for the same duration. Tumor tissue (sample B) was then retrieved from the tumor after resection. Changes in the expression levels of inflammatory cytokines (TNF-α, interleukin 8 or chemokine (C-X-C motif) ligand (CXCL8), stromal cell-derived factor 1 (SDF1a), chemokine (C-X-C motif) ligand 6 (CXCL6), chemokine (C-X-C motif) ligand (CXCL2), myeloperoxidase (MPO), and CXCL1) were assessed during the perioperative course. RESULTS: TNF-α expression differed after intervention between the two groups (immune group 31.63 ± 13.28; control group 21.54 ± 6.84; p = 0.049) and prior to and after intervention in the control group (prior to intervention 35.68 ± 24.41; after intervention 21.54 ± 6.84; p = 0.038). Changes in CXCL8 expression in the control group occurred prior to and after intervention (prior to intervention 2975.93 ± 1484.04; after intervention 1584.85 ± 1659.84; p = 0.041). CXCL1 expression was increased in the immune group and decreased in the control group (immune group 2698.27 (1538.14-5124.70); control group 953.75 (457.85-1534.60); p = 0.032). In both groups, a decrease in superficial neutrophil infiltration was observed, but this was only statistically significant in the immune group. There was no impact of the observed differences between the two groups on surgical outcomes (morbidity, length of stay, readmissions). CONCLUSIONS: Immunonutrition in the preoperative period compared with standard nutritional support may influence inflammatory cytokine expression and leukocyte infiltration in patients with colorectal cancer.

Image analysis discloses differences in nuclear parameters between ERG+ and ERG- prostatic carcinomas.

Prostatic carcinoma (PC) is the most frequent urologic cancer and one of the most frequent cancers in males; it is a heterogeneous disease, in terms of molecular features, morphology and prognosis. About half of cases depends on TMPRSS2-ETS translocation which leads to a production of ERG transcription factor. ERG+ and ERG- cancers seem to differ in a number of features, which could lead to an altered nuclear structure; the aim of the study was to test this hypothesis. The material consisted of total 39 PC cases, representing ERG+ and ERG-, as well as Gleason pattern 3 and 4. Filtering by color deconvolution and automatic segmentation were used, and the properly detected nuclei were manually selected. From each case fifty nuclei were obtained; then geometric features and texture parameters were assessed. The analysis of the collected data showed differences both between ERG+/ERG- and Gleason pattern 3 and 4 cases in most of the features analyzed. Our results suggest that indeed the ERG status, thus likely TMPRSS2-ETS translocation, has an impact on morphology of nuclei in PC, and their differences are evident enough to be detectable by image analysis.

Early closure of the protective ileostomy after rectal resection should become part of the Enhanced Recovery After Surgery (ERAS) protocol: a randomized, prospective, two-center clinical trial.

INTRODUCTION: Protective loop ileostomy (PLI) is used to reduce the anastomotic leak rate after resection of the rectum. It is an effective, yet burdensome procedure contradicting the aims of enhanced recovery after surgery (ERAS) by slowing down recovery. Early closure (EC) of the PLI has the potential to change the situation, and it should become part of ERAS. AIM: To analyze the effectiveness of EC in ERAS patients. MATERIAL AND METHODS: A randomized clinical trial was performed between October the 1st, 2016 and December the 31st, 2017. Fifty-eight adult patients (24 females, 34 males, mean age: 55.7 and 56.2) operated on for rectal carcinoma according to the ERAS protocol with PLI were randomly assigned to the late (L) or early (E) closure group (14 days after discharge). Time to start adjuvant chemotherapy, complication rate, and health care costs were analyzed. RESULTS: There were no significant differences between groups regarding the length of surgery (83.2 ±15.9 vs. 87.1 ±21.7 min, in E and L, respectively), intraoperative blood loss (15.2 ±7.5 vs. 17.3 ±11.1 ml, respectively), median hospital stay, or the time to pass flatus and stool. The difference in the time needed to start the adjuvant treatment (38.7 ±5.7 vs. 33.2 ±5.8 days, p < 0.01), was compensated by the reduction of time living with a stoma (17.2 vs. 299.0 days) and health care costs: (43.68 vs. 698.42 USD). CONCLUSIONS: Early closure is a safe and effective therapeutic approach, improving the recovery. Therefore it should be implemented as part of the ERAS protocol for rectal cancer patients.

Is It Possible to Maintain High Compliance with the Enhanced Recovery after Surgery (ERAS) Protocol?-A Cohort Study of 400 Consecutive Colorectal Cancer Patients.

The aim of our study was to evaluate the implementation and degree of adherence to the Enhanced Recovery after Surgery (ERAS) protocol in a group of 400 patients operated laparoscopically for colorectal cancer, and to assess its impact on the short-term results. The prospective study included patients with histologically confirmed colorectal cancer undergoing elective laparoscopic resection from years 2012 to 2017. For the purpose of further analysis, patients were divided into four groups: 100 consecutive patients were in each group. There were no statistically significant differences between groups in demographic parameters. The mean compliance with the ERAS protocol in the entire study group was 84.8%. Median adherence differed between the groups 76.9% vs. 92.3% vs. 84.6% vs. 84.6%, respectively (p < 0.0001). There were statistically significant differences between groups in the tolerance of oral diet (54% vs. 83% vs. 83% vs. 64%) and mobilization (74% vs. 92% vs. 91% vs. 94%) on the first postoperative day. In subsequent groups, time to first flatus decreased (2.5 vs. 2.1 vs. 2.0 vs. 1.7 days, p = 0.0001). There were no statistical differences in the postoperative morbidity rate between groups (p = 0.4649). The median length of hospital stay in groups was 5 vs. 4 vs. 4 vs. 4 days, respectively (p = 0.0025). Maintaining high compliance with the ERAS protocol is possible, despite the slight decrease that occurs within a few years after its implementation. This decrease in compliance does not affect short-term results, which are comparable to those shortly after overcoming the learning curve.

SOX-2, but not Oct4, is highly expressed in early-stage endometrial adenocarcinoma and is related to tumour grading.

BACKGROUND: Expression of SOX-2 and Oct4 as markers for the identification of cancer stem cells (CSCs) has been revealed in several malignancies. In this study, the co-expression of SOX-2 and Oct4 and their correlation with clinicopathological features of endometrial adenocarcinomas (EACs) was investigated. METHODS: SOX-2 and Oct4 expression was assessed by immunohistochemistry in 27 (39.13%) stage IA and in 42 (60.87%) stage IB International Federation of Gynaecology and Obstetrics (FIGO) EACs and related to the clinicopathological features of patients. RESULTS: The expression of SOX-2 was confirmed in 62/69 tumour specimens compared to Oct4 expression in 46/69 specimens (P = 0.015) and no difference in median staining intensity between SOX-2 and Oct-4 was observed. The highest median SOX-2 expression was found in high-grade (G3) EAC samples compared to moderate-grade (G2) EAC specimens (P = 0.020) and low-grade (G1) specimens (P = 0.008), while no differences in median Oct4 expression in EAC samples according to grading were present. In G3 specimens, significantly higher median SOX-2 expression was noted compared to Oct4 (P = 0.002). SOX-2 and Oct4 co-expression was observed only in G1 EAC (R: 0.51; P = 0.031). Age of EAC diagnosis was positively correlated with SOX-2 expression (b = 0.193; R(2) = 10.83%; P = 0.003) but not to age of menarche, menopause, parity or body mass index. CONCLUSIONS: There is no need to use SOX-2 expression as a poor outcome predictor in stage I EAC, and SOX-2 expression should be analysed in more advanced stages.