PYCR1, BANF1, and STARD8 Expression in Gastric Carcinoma: A Clinicopathologic, Prognostic, and Immunohistochemical Study.

BACKGROUND: It will be important to understand the molecular pathways of gastric cancer (GC) occurrence and progression, thus detecting predictive and prognostic biomarkers of GC. Pyrroline-5-carboxylate reductase 1 (PYCR1) was upregulated in many cancers, suggesting its possible roles in carcinogenesis and tumor metastases. Barrier-of-autointegration factor 1 (BANF1) is a protein family that plays essential roles in maintaining the integrity of an intact cellular genome. Rho-GTPs are molecular switches that control many signal transduction pathways in normal cells, including 3 subgroups from 1 to 3 (DLC1-3). DLC-3, known as StAR-related lipid transfer domain protein 8 (STARD8), and its role in cancers were not sufficiently studied. The study aimed to investigate the significance of PYCR1, BANF1, and STARD8 protein expression in GC tissues and normal gastric mucosa retrieved from patients with GC to detect prognostic roles of expression. PATIENTS AND METHODS: Specimens were collected from 100 patients with gastric carcinoma. After the application of the inclusion criteria of the study, we prepared 100 paraffin blocks from samples of the 100 included patients; each block included samples from gastric carcinoma and adjacent non-neoplastic gastric mucosa. We assessed the expression of PYCR1, BANF1, and STARD8 using immunohistochemistry in all studied samples. We followed patients for the detection of disease progression and survival rates. We correlate PYCR1, BANF1, and STARD8 expression with clinical, pathologic, and prognostic parameters. RESULTS: Overexpression of PYCR1 and BANF1 and decreased expression of STARD8 was found in gastric carcinoma tissues than adjacent non-neoplastic gastric mucosa ( P <0.001), and was positively associated with high grade ( P =0.006), depth of tumor invasion, presence of lymph nodes metastases and advanced stage ( P =0.001), high incidence of GC progression, recurrence, unfavorable disease-free survival ( P =0.003) and unfavorable overall survival rates ( P <0.001). Thus, it was revealed that; in univariate and multivariate analyses, levels of PYCR1, BANF1, and STARD8 are associated with the overall survival rate of GC patients. CONCLUSIONS: We showed that overexpression of PYCR1 and BANF1 and decreased expression of STARD8 in GC tissues was associated with poor prognosis and GC progression.

Protein Expression of NEK2, JMJD4, and REST in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical, Pathological, and Prognostic Findings.

Background & Objective: Cells of renal cell carcinoma (RCC) are resistant to the most currently used chemotherapeutic agents and targeted therapies; hence, we evaluated the expression of NEK2, JMJD4, and REST in cases of clear cell renal cell carcinoma (ccRCC) and benign adjacent tissues of kidney to detect associations between their expression and clinicopathological features, prognostic data, tumor recurrence, and survival rates. Methods: We collected 200 samples including tumoral and adjacent non-neoplastic tissues related to 100 ccRCC patients. All samples were evaluated for the expression of NEK2, JMJD4, and REST, and the patients were followed up for about 5 years. Tumor recurrence and survival data were documented and analyzed. Results: NEK2 and JMJD4 expression showed increase in ccRCC tissues (P=0.002 and 0.006), while REST was downregulated (P<0.001). The elevated expression of NEK2 was positively related ro the tumor size (P=0.015), higher grades (P=0.002), higher stages (P=0.013), distant spread (P=0.004), tumor recurrence, shorter progression-free survival (PFS) rate, and overall survival (OS) rate (P<0.001). Likewise, the high expression of JMJD4 showed positive correlation with the tumor size (P=0.047), higher grades (P=0.003), higher stages (P=0.043), distant spread (P=0.001), tumor recurrence, shorter PFS rate, and OS rate (P<0.001). Conversely, low expression of REST demonstrated positive relationship with the tumor size, higher grades, higher stages, distant spread, tumor recurrence, and shorter PFS and OS rates (P<0.001). Conclusion: Overexpression of NEK2 and JMJD4 and downregulation of REST may be noted in malignant renal tissues compared to benign renal tissues and may be correlated with unfavorable pathological findings, poor clinical parameters, and poor patient outcomes.

Bladder preservation by neoadjuvant chemotherapy followed by concurrent chemoradiation for muscle-invasive bladder cancer.

Introduction: In Egypt, bladder cancer (BC) represents about 8.7% of cancers in both sexes. In Egyptian men, it accounts for over 30% of all cancers, which makes it the second most frequent cancer. The standard curative treatment for patients with muscle-invasive bladder cancer (MIBC) has been radical cystectomy (RC) with urinary diversion and pelvic lymphadenectomy. Concomitant chemoradiation therapy (CCRT) in MIBC appears to produce results that are comparable to those of RC. Material and methods: Between January 2018 and March 2021, 34 BC- diagnosed patients, who refused RC, were enrolled. They received transurethral resection of the bladder tumour (TURBT) followed by 3 cycles of neoadjuvant chemotherapy (NACT) with gemcitabine, cisplatin, and CCRT. Concomitant chemoradiation therapy with cisplatin, as a chemosensitizer, was administered to patients who experienced a complete response (CR) and a partial response (PR) ≥ 50%. Results: Following NACT, CCRT was given to 27 patients (79.45%) who had either a PR > 50% or CR. Seven patients (20.5%) showed PR below 50%, stable disease, or progressive disease; 4 of them underwent RC followed by postoperative radiation. The average follow-up period was 46 months (range: 6-52 months). Twenty-three patients (67.6%) were still alive at the last check-up. Disease-free survival and 3-year overall survival were 70.8% and 65.1%, respectively. Conclusions: Bladder preservation provides survival rates comparable to those of MIBC patients, but with a higher quality of life. The findings show good survival rates without metastasis; nevertheless, more multicentre trials with larger sample sizes and longer follow-up periods are required to confirm these findings.

Prognostic roles and survival benefits of endoscopic resection versus surgical resection in the management of malignant colon polyps

Background: Due to few sufficient data regarding the comparison between endoscopic and surgical resection of malignant colorectal polyps regarding outcomes and survival benefits, there are no clear guidelines of management strategies of malignant colorectal polyps. The aims of the present study were to compare endoscopic resection alone and surgical resection in patients with malignant polyps in the colon (T1N0M0) readings advantages, disadvantages, recurrence risks, survival benefits, and long-term prognosis to detect how management strategy affects outcome. Patients and methods: we included 350 patients. All included patients were divided into 2 groups; the first group included 100 patients who underwent only endoscopic polypectomy and the second group included 250 patients who underwent endoscopic polypectomy followed by definitive surgical resection after histopathological diagnosis. We followed all patients for about 5 years, ranging from 18 to 55 months. The primarily evaluated parameters are surgical consequences and patients' morbidity. The secondary evaluated parameters are recurrence risks, recurrence free survival, and overall survival rates. Results: The age of patients who underwent polypectomy is usually younger than the surgical group, males have more liability to polypectomy in comparison with females. Patients with tumors in the left colon have more liability to polypectomy in comparison with the right colon (p< 0.0001). Tumor factors associated with more liability to surgical resection are presence of lymphovascular invasion, high grade, and poor tumor differentiation (p< 0.0001). The management strategy was the most significant predictor of overall and recurrence free survival rates in patients with malignant colon polyps (p< 0.001). Conclusions: We found that survival benefits and lower incidence of recurrence are detected in the surgical resection group more than in the polypectomy group. (AU)

Risk factors and outcomes of occurrence of anastomotic leakage and reoperations for its management after colorectal surgery

Background: Anastomotic leakage (AL) is still the most annoying postsurgery complication after colorectal resection due to its serious complications up to death. Limited data were available regarding differences in AL incidence, management, and consequences for different types of colorectal resection. The aim of the present work was to evaluate differences in incidence of AL, incidence of postoperative complications, and length of hospital stay in a large number of patients who underwent elective colorectal resection for management of colorectal lesions. In addition to detect when and what type of reoperation for management of AL occur after colorectal resection. Patients: All 250 included patients underwent elective surgeries for colorectal resection with performance of primary anastomosis for management of colorectal neoplastic and non-neoplastic diseases in the period between May 2016 and July 31, 2021. We followed the patients for 90 days; we registered the follow-up findings. Results: the rates of AL occurrence were variable after the different procedures. The lowest rate of AL occurrence was found in patients who underwent right hemicolectomy, then in patients who underwent sigmoidectomy, left hemicolectomy, transversectomy and anterior resection (p= 0.004). A stoma was frequently performed during reoperation (79.5%) which was significantly different between different procedures: 65.5% in right hemicolectomy, 75.0% in transversectomy, 85.7% in left hemicolectomy, and 93.0% in sigmoid resection (p< 0.001). Conclusion Rates, types, time of occurrence and severity of AL vary according to the type of colectomy performed and selective construction of stoma during AL reoperation is currently safely applied with comparable mortality rates for patients who did and who did not have a stoma after reoperation. (AU)

Surgical roles in the management of metachronus para-aortic lymph node recurrence and synchronous para-aortic lymph node metastasis in colorectal cancer patients

Background: The relative rarity of synchronous para-aortic lymph node (PALN) metastasis (SPM) and metachronous PALN recurrence (MPR) in colorectal carcinoma (CRC) patients leads to a limited number of studies on patient management, and no treatment guidelines have been established to date. Objective: To assess the prognostic, predictive roles, and long-term outcomes of different management strategies for isolated MPR and SPM in CRC patients to establish the best one. Materials and Methods: We included 35 CRC patients with isolated MPR and 25 patients with isolated SPM who underwent curative R0 resection. We performed PALN dissection (PALND) in 15 cases in MPR group and in 10 cases in the SPM group; all remaining patients in both groups underwent chemoradiotherapy (CRT) without further surgical intervention. During the study period of about 5 years, we compared the patients who underwent PALND and those who underwent CRT. Results: The overall survival and recurrence-free survival rates were significantly longer in patients who underwent PALND (p = 0.049 and 0.036 respectively). (AU)

Prognostic and clinicopathological implications of expression of Beclin-1 and hypoxia-inducible factor 1α in serous ovarian carcinoma: an immunohistochemical study.

Serous ovarian carcinoma (SOC) is an ovarian cancer with a high fatality rate. Therefore, a lot of researchers have tried to identify novel prognostic biomarkers which might improve the patient prognosis. The aims of the study were to detect the tissue protein expression of Beclin-1 in addition to HIF-1α in SOC patients, to evaluate the relationship between their expression, the clinicopathological parameters, patients' prognosis, and the relation to chemotherapy resistance in SOC. We evaluated the expression of Beclin-1 in addition to HIF-1α in 60 patients with SOC using immunohistochemistry, followed all patients for about 36 months, analyzed associations between both markers' expression, clinicopathological data, and patients' prognosis. Beclin-1 expression was related to low grade (p = 0.002), early SOC stage, absence of peritoneal spread (p = 0.006), and absence of lymph nodes, and distant metastases (p = 0.004 and < 0.001 respectively), while HIF-1α expression was associated with higher grade and stage (p = 0.007), and presence of nodal and distant metastases (p < 0.001 and = 0.012 respectively). High Beclin-1 expression and low HIF-1α expression were positively associated with good response to chemotherapy (p = 0.047 and p = 0.022 respectively), a lower recurrence rate after successful therapy (p = 0.006 and < 0.001 respectively), and increased three-year recurrence-free and overall survival rates (p < 0.001). In SOC patients; Beclin-1 is a good prognostic marker, while HIF-1α is a poor prognostic marker.

The Diagnostic and Prognostic Roles of Combined Expression of Novel Biomarkers in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma: An Immunohistochemical Study.

BACKGROUND & OBJECTIVE: Diagnosis and discrimination of lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC) is critical to select the appropriate treatment regimen as recently targeted therapies require accurate subtyping of nonsmall-cell lung carcinoma (NSCLCs). There are currently several biomarkers that could be used for differentiation between LUAD and LUSC, but they have less sensitivity, specificity, and clinical applicability. The aim of this study was to assess the diagnostic and prognostic values of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin tissue expression in the tissues retrieved from LUAD and LUSC patients using immunohistochemistry. METHODS: The current study was performed on the samples retrieved from sixty primary lung masses that were diagnosed as LUAD and LUSC. Immunohistochemistry was performed by using a panel of CLCA2, SPATS2, and ST6GALNAC1. We assessed the diagnostic roles of the studied markers in the discrimination between LUAD and LUSC and their prognostic values. RESULTS: SPATS2 and CLCA2 were expressed higher in LUSC than LUAD. ST6GALNAC1 and Adipophilin showed higher expression in LUAD than LUSC (P <0.001). The sensitivity and specificity of CLCA2, SPATS2, ST6GALNAC1 and Adipophilin in adequate subtyping and reaching the accurate diagnosis was 100%. We found only significant difference in survival rate between the patients with negative and positive CLCA2 expression (P=0.038 and P=0.019, respectively). CONCLUSION: The combination of biomarkers of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin may lead to an appropriate subtyping of lung cancer and reaching accurate diagnosis with the highest sensitivity and specificity.

Prognostic Significances of NEDD-9 and FOXL-1 Expression in Intestinal Type Gastric Carcinoma: an Immunohistochemical Study.

BACKGROUND: Gastric cancer (GC) is mostly diagnosed at advanced stage, so prognosis is poor. Therefore, it is necessary to understand the molecular mechanism of GC development to design new targeted treatment to improve the prognosis of gastric cancer patients. AIM OF THE WORK: To assess the prognostic value of NEDD-9 and FOXL-1 expression in intestinal type gastric cancer patients, as well as their relationship to clinicopathologic features of the disease and patients outcome. PATIENTS AND METHODS: This is a retrospective study; we included 50 sections from formalin-fixed, paraffin-embedded tissue samples which included intestinal type GC and adjacent non-neoplastic gastric mucosa in the same block that were subjected to immunohistochemistry with anti-NEDD-9 and anti-FOXL-1 antibody. Patients were retrospectively followed up for about 5 years for assessment of tumor progression and survival in relation to marker expression. RESULTS: High NEDD-9 and low FOXL-1 expression were found in intestinal type GC more than adjacent non-neoplastic mucosa (p < 0.001). NEDD-9 high expression and FOXL-1 low expression were associated with presence of helicobacter pylori gastritis (p = 0.010, 0.049), high grade (p = 0.007, 0.004), high stage (p < 0.001), presence of distant metastases (p = 0.029, 0.021), poor DFS (p = 0.003), and OS rates (< 0.001). CONCLUSION: NEDD-9 overexpression and FOXL-1 deficiency in intestinal type GC can help in prediction of tumor prognosis and it can guide the selection of patients for future therapies in gastric carcinoma.