Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer.

TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor (EGFR) and cyclin D1 were assessed in 96 tissue samples, including non-tumorous tissue, adenoma, and carcinoma. Then, the prognostic impact of EGFR and cyclin D1 was retrospectively investigated in 316 patients who underwent R0 resection for GC. EGFR positivity increased as gastric tissue became malignant, and cyclin D1 positivity was increased in all the tumorous tissues. However, there was no survival difference caused by the EGFR positivity, while the cyclin D1-postive group had worse overall survival (OS) than the cyclin D1-negative group in stage I GC (10-year survival rate (10-YSR): 62.8% vs. 86.5%, p = 0.010). In subgroup analyses for the propensity score-matched (PSM) cohort, there were also significant differences in the OS according to the cyclin D1 positivity in stage I GC but not in stage II and III GC. Upon multivariate analysis, cyclin D1 positivity was an independent prognostic factor in stage I GC. In conclusion, cyclin D1 may be a useful biomarker for predicting prognosis in stage I GC.

Helicobacter pylori Antigens Inducing Early Immune Response in Infants.

To identify the Helicobacter pylori antigens operating during early infection in sera from infected infants using proteomics and immunoblot analysis. Two-dimensional (2D) large and small gel electrophoresis was performed using H. pylori strain 51. We performed 2D immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibody immunoblotting using small gels on sera collected at the Gyeongsang National University Hospital from 4-11-month-old infants confirmed with H. pylori infection by pre-embedding immunoelectron microscopy. Immunoblot spots appearing to represent early infection markers in infant sera were compared to those of the large 2D gel for H. pylori strain 51. Corresponding spots were analyzed by matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS). The peptide fingerprints obtained were searched in the National Center for Biotechnology Information (NCBI) database. Eight infant patients were confirmed with H. pylori infection based on urease tests, histopathologic examinations, and pre-embedding immunoelectron microscopy. One infant showed a 2D IgM immunoblot pattern that seemed to represent early infection. Immunoblot spots were compared with those from whole-cell extracts of H. pylori strain 51 and 18 spots were excised, digested in gel, and analyzed by MALDI-TOF-MS. Of the 10 peptide fingerprints obtained, the H. pylori proteins flagellin A (FlaA), urease ß subunit (UreB), pyruvate ferredoxin oxidoreductase (POR), and translation elongation factor Ts (EF-Ts) were identified and appeared to be active during the early infection periods. These results might aid identification of serological markers for the serodiagnosis of early H. pylori infection in infants.

Immunohistochemical Expressions of MUC2, MUC5AC, and MUC6 in Normal, Helicobacter pylori Infected and Metaplastic Gastric Mucosa of Children and Adolescents.

OBJECTIVES: The aim of this study was to investigate expression of gastric mucins in children and adolescents and to assess their relations with age and Helicobacter pylori (H. pylori) infection. METHODS: Gastric biopsies were collected from 259 pediatric and adulthood patients with gastrointestinal symptoms among all of patients undergone gastroduodenoscopy from 1990 to 2004 at Gyeongsang National University hospital and assorted based on H. pylori infection, age, and intestinal metaplasia as follows; H. pylori infection before 5 years of age or not, H. pylori infection between 5 and 9 years of age or not, H. pylori infection between 10 and 14 years of age or not, H. pylori infection between 20 and 29 years of age or not and intestinal metaplasia between 21 and 35 years of age. Total 810 tissue slides from the subjects were examined regarding expressions of Mucin2 (MUC2), Mucin5AC (MUC5AC), and Mucin6 (MUC6) in nine groups using immunohistochemical stains. A semiquantitative approach was used to score the staining extent of tissue slide. RESULTS: Increased expressions of MUC2, MUC5AC, and MUC6 were noted in intestinal metaplasia compared with subjects infected with H. pylori between 20 and 29 years. Gastric expressions of MUC5AC were decreased in older than 5 years with H. pylori compared with in older than 5 years without H. pylori (p < .001). Expressions of MUC2 and MUC6 did not change significantly by H. pylori status. Some nuclear expressions of MUC2 and MUC6 were noted in children without intestinal metaplasia. CONCLUSIONS: MUC5AC might be affected by chronic H. pylori infection. In addition to biomarkers for intestinal metaplasia or prognostic factors for gastric cancer in adults, MUC2 and MUC6 in children might have an another role, based on ectopic gastric nuclear expressions of MUC2 and MUC6 in children without intestinal metaplasia.

The prognostic value of immunohistochemical markers for oral tongue squamous cell carcinoma.

The objective of the study was to examine the prognostic value of hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase-IX (CA-IX), cyclooxygenase-2 (COX-2), Ki-67, and erythropoietin receptor in patients with oral tongue squamous cell carcinoma. Immunohistochemical analysis of marker expression was performed on tissue samples from 25 patients with tongue squamous cell carcinoma. The Kaplan-Meier method, univariate and multivariate analyses, and the Cox proportional hazards model were used to examine associations between patient and tumor characteristics, and the immunohistochemical results and disease-specific survival. There was no association between the expression of the five markers and disease-specific survival, and there was no statistically significant difference in the hazards ratio according to postoperative radiotherapy. There was no correlation between marker expression and prognosis. There was no association between marker expression and radioresistance or disease-specific survival. Therefore, HIF-1α, CA-IX, COX-2, Ki-67, and erythropoietin receptor are not suitable prognostic markers for tongue squamous cell carcinoma.

VEGF-C mediates RhoGDI2-induced gastric cancer cell metastasis and cisplatin resistance.

Rho GDP dissociation inhibitor 2 (RhoGDI2) expression is correlated with tumor growth, metastasis and chemoresistance in gastric cancer. However, the mechanisms by which RhoGDI2 promotes tumor cell survival and metastasis remain unclear. In this study, we clearly demonstrate that RhoGDI2 upregulates VEGF-C expression and RhoGDI2 expression is positively correlated with VEGF-C expression in human gastric tumor tissues as well as parental gastric cancer cell lines. VEGF-C depletion suppressed RhoGDI2-induced gastric cancer metastasis and sensitized RhoGDI2-overexpressing cells to cisplatin-induced apoptosis in vitro and in vivo. Secreted VEGF-C enhanced gastric cancer cell invasion and conferred cisplatin resistance to RhoGDI2-overexpressing cells. We also show that RhoGDI2 positively regulates Rac1 activity in gastric cancer cells. Inhibition of Rac1 expression suppressed RhoGDI2-induced VEGF-C expression, and this inhibition was associated with decreased invasiveness and increased sensitivity to cisplatin in RhoGDI2-overexpressing cells. Our results indicate that RhoGDI2 might be a potential therapeutic target for simultaneously reducing metastasis risk and enhancing chemotherapy efficacy in gastric cancer.

OCT-1 overexpression is associated with poor prognosis in patients with well-differentiated gastric cancer.

Octamer transcription factor-1 (OCT-1) is a well-known transcription factor that is reportedly overexpressed in intestinal metaplasia and gastric carcinoma in the intestine. In this study, we investigated OCT-1 overexpression as a prognostic factor for gastric cancer. The association between OCT-1 overexpression (detected using immunohistochemistry) and clinicopathological features including survival was evaluated. In vitro gain-of-function approaches were utilized to assess the function of OCT-1 in malignancy. Analysis of OCT-1 expression in patients with gastric cancer with well-differentiated carcinoma as per the World Health Organization classification showed that OCT-1 overexpression was correlated with advanced tumor invasion (58.8 % of patients with advanced tumor invasion vs. 21.2 % of patients with early tumor invasion; p<0.01), lymph node metastasis (63.9 % of patients with metastasis vs. 24.1 % of those without; p=0.015), and cancer recurrence (83.3 % of patients with recurrence vs. 25.4 % of those without; p<0.01), as well as a lower survival rate (62.8 vs. 87.9 Mo; p<0.01). However, there were no significant differences in the levels of OCT-1 expression in gastric cancer patients with other carcinoma types (p>0.05). Furthermore, we found that the proliferation rate of OCT-1-overexpressing MKN-45 cells was higher than that of the control cells. OCT-1 overexpression may be a marker for poor prognosis in patients with well-differentiated gastric adenocarcinoma.

Relationship between headache and mucosal mast cells in pediatric Helicobacter pylori-negative functional dyspepsia.

BACKGROUND: Although many patients with functional dyspepsia experience headache concurrently with dyspeptic symptoms, studies suggesting mechanisms underlying this phenomenon are limited. Herein, we explore the relationship between gastrointestinal inflammatory cells and presence of headache associated with dyspeptic symptoms in children with HELICOBACTER PYLORI -negative functional dyspepsia. METHODS: Fifty-six patients with H. PYLORI -negative functional dyspepsia underwent upper endoscopy with biopsy to investigate recurrent epigastric pain or discomfort. Patients were divided into two groups according to self-reported presence of headache associated with dyspeptic symptoms. Inflammatory cells including mast cells, and enteroendocrine cells in the gastroduodenal mucosa were evaluated. Associations between headache presence and cellular changes in the gastroduodenal mucosa were examined. RESULTS: Headache was not associated with the grade of lymphocytes, neutrophil infiltration, or enteroendocrine cell density in the gastroduedenal mucosa. However, headache was significantly associated with high mast cell density in the body (27.81 ± 8.71 vs. 20.30 ± 8.16, P < 0.01) and duodenum (23.16 ± 10.40 vs. 14.84 ± 5.88, P < 0.01). CONCLUSIONS: Presence of headache associated with dyspeptic symptoms is strongly related to mucosal mast cell density in pediatric patients with H. PYLORI -negative functional dyspepsia. Thus, our results may help clinicians understand and treat headache during dyspeptic symptoms in such pediatric patients.

Changing pattern of antibiotic resistance of Helicobacter pylori in children during 20 years in Jinju, South Korea.

BACKGROUND: The antimicrobial resistance capability of Helicobacter pylori is one of the critical factors in the failure to treat this pathogen. The purpose of this study was to investigate the changing pattern of primary antibiotic resistance rates in children in the southern central part of South Korea from 1990 to 2009. METHODS: H. pylori strains were isolated from children who had undergone upper endoscopy at Gyeongsang National University Hospital, including 58 children from 1990-1994 and 33 children from 2005-2009. The susceptibility of H. pylori strains to erythromycin, clarithromycin, azithromycin, amoxicillin, tetracycline, metronidazole, furazolidone, levofloxacin, ciprofloxacin, moxifloxacin, and rifabutin was tested using the serial twofold agar dilution method. RESULTS: The resistance rate to erythromycin increased significantly from 13.8% in 1990-1994 to 33.3% in 2005-2009 (P = 0.032). Clarithromycin resistance increased from 6.9% to 18.2%. Metronidazole resistance decreased from 32.8% to 27.3%. The minimum inhibitory concentration of azithromycin and erythromycin showed definite shifts to higher concentrations in 2005-2009 compared with the strains sampled in 1990-1994 (P = 0.021 and P = 0.025, respectively). The frequency of both macrolide- and metronidazole-resistant strains was 13.8% in 1990-1994 and 15.2% in 2005-2009. No associations were detected between multidrug-resistant strains and the two study periods. CONCLUSIONS: The antibiotic resistance rates of H. pylori in Jinju had a different pattern to other regions. The antibiotic resistance rates of H. pylori showed geographic variation, and local data should be provided as a guideline for treating H. pylori infection.

Pyrophosphatase overexpression is associated with cell migration, invasion, and poor prognosis in gastric cancer.

Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate to form orthophosphate. Pyrophosphate can substitute for ATP under certain circumstances. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer, and PPase was identified as a potential gastric tumor-specific marker; it was therefore selected for further study. Clinicopathological analysis, using proteomic analysis and immunohistochemistry, was used to validate PPase as a prognostic marker in gastric cancers. Proteomic analysis showed that PPase was overexpressed in patients with lymph node (LN) metastases and high tumor node metastasis (TNM) stages (p < 0.05). Based on immunohistochemistry, patients whose tumors overexpressed PPase had higher T stages, LN metastasis, a higher TNM stage, a higher cancer recurrence rate, and shorter survival times than patients whose tumors exhibited PPase underexpression (p < 0.05). Gain-of-function and loss-of-function approaches were employed to examine the malignant phenotypes of PPase-overexpressing or PPase-depleted cells. A decrease in PPase expression caused a significant decrease in gastric cancer cell migration and invasion in vitro, whereas forced overexpression of PPase enhanced migration but not invasion. Our findings indicate that PPase is involved in gastric tumor progression and that PPase may be a useful marker for poor prognosis of human gastric cancers.

Prognostic value of sonic hedgehog protein expression in gastric cancer.

OBJECTIVE: Sonic hedgehog is produced in gastric epithelial cells and plays a crucial role in parietal cell function and the regulation of gastric epithelial cell differentiation. Emerging evidence suggests that the sonic hedgehog pathway is not only involved in the development of cancers but also in their progression and aggressiveness. METHODS: To assess its prognostic value in gastric cancer, sonic hedgehog protein expression was measured by immunohistochemistry in a clinically annotated tissue microarray comprising 319 human gastric cancer specimens. Cytoplasmic sonic hedgehog expression was scored from 0 to 4, reflecting the percentage of sonic hedgehog-positive cells. RESULTS: Specimens were classified into two groups according to their sonic hedgehog score: those with a score ranging from 0 to 3 were considered low expressers and those with a score of 4 were considered overexpressers. The sonic hedgehog overexpression group included more patients with early gastric cancer than the low sonic hedgehog expression group (25.9 vs. 74.1%, P=0.000). Sonic hedgehog expression was lower in patients with lymph node metastasis than in patients without lymph node metastasis (31.4 vs. 68.4%, P=0.02). Similarly, patients with a lower TNM stage showed significantly higher sonic hedgehog expression. In addition, the survival time of patients with sonic hedgehog overexpression was significantly prolonged (69.27±1.39 months) compared with that of patients with low sonic hedgehog expression (61.23±2.04 months, log-rank test, P=0.03). CONCLUSIONS: These results indicate that sonic hedgehog overexpression may be a marker of good prognosis in gastric cancer.

An indigenous case of intestinal capillariasis with protein-losing enteropathy in Korea.

We encountered an indigenous case of intestinal capillariasis with protein-losing enteropathy in the Republic of Korea. A 37-year-old man, residing in Sacheon-si, Gyeongsangnam-do, admitted to the Gyeongsang National University Hospital (GNUH) due to long-lasting diarrhea, abdominal pain, anasarca, and weight loss. He recalled that he frequently ate raw fish, especially the common blackish goby (Acanthogobius flavimanus) and has never been abroad. Under the suspicion of protein-losing enteropathy, he received various kinds of medical examinations, and was diagnosed as intestinal capillariasis based on characteristic sectional findings of nematode worms in the biopsied small intestine. Adults, juvenile worms, and eggs were also detected in the diarrheic stools collected before and after medication. The clinical symptoms became much better after treatment with albendazole 400 mg daily for 3 days, and all findings were in normal range in laboratory examinations performed after 1 month. The present study is the 6th Korean case of intestinal capillariasis and the 3rd indigenous one in the Republic of Korea.

Transcriptome Analysis and the Prognostic Role of NUDC in Diffuse and Intestinal Gastric Cancer.

INTRODUCTION: There have been few studies about gene differences between patients with diffuse-type gastric cancer and those with intestinal-type gastric cancer. The aim of this study was to compare the transcriptomes of signet ring cell gastric cancer (worst prognosis in diffuse-type) and well-differentiated gastric cancer (best prognosis in intestinal-type); NUDC was identified, and its prognostic role was studied. MATERIALS AND METHODS: We performed next-generation sequencing with 5 well-differentiated gastric cancers and 3 of signet ring cell gastric cancer surgical samples. We performed gene enrichment and functional annotation analysis using the Database for Annotation, Visualization and Integrated Discovery bioinformatics resources. Immunohistochemistry was used to validate NUDC expression. RESULTS: Overall, 900 genes showed significantly higher expression, 644 genes showed lower expression in signet ring cell gastric cancer than in well-differentiated gastric cancers, and there was a large difference in adhesion, vascular development, and cell-to-cell junction components between the 2 subtypes. We performed variant analysis and found 52 variants and 30 cancer driver genes, including NUDC. We analyzed NUDC expression in gastric cancer tissue and its relationship with prognosis. Cox proportional hazard analysis identified T stage, N stage, and NUDC expression as independent risk factors for survival (P < 0.05). The overall survival of the NUDC-positive group was significantly higher (53.2 ± 0.92 months) than that of the NUDC-negative group (44.6 ± 3.7 months) (P = 0.001) in Kaplan-Meier survival analysis. CONCLUSION: We found 30 cancer driver gene candidates and found that the NUDC-positive group showed significantly better survival than the NUDC-negative group via variant analysis.

Unusual gastrointestinal metastases from an alveolar soft part sarcoma.

Alveolar soft part sarcoma (ASPS) is a rare subtype of soft tissue sarcoma that occurs predominantly in young patients. Despite its relatively indolent course, it generally has a poor prognosis with widespread metastases. The common metastatic sites from an ASPS include the lung, brain and bone. However, metastasis of an ASPS to the gastrointestinal tract is extremely rare. Here, we report a rare case of upper gastrointestinal bleeding and jejunal intussusception due to gastrointestinal metastases from an ASPS.

ERH overexpression is associated with decreased cell migration and invasion and a good prognosis in gastric cancer.

BACKGROUND: The enhancer of rudimentary homolog (ERH) protein is implicated in transcriptional regulation, cell cycle progression, and malignancy. We previously conducted a proteomics analysis using gastric cancer (GC) tissues and identified ERH as a biomarker candidate. The aim of this study was to investigate whether ERH may be useful as a prognostic marker for GC. METHODS: Surgically resected GC tissue specimens were obtained from 327 patients who underwent gastrectomy at Gyeongsang National University Hospital. Immunohistochemistry (IHC) was used to validate ERH as a prognostic marker in these tissues. SNU601 and MKN74 cells with siRNA-mediated knockdown of ERH expression and ERH-overexpressing SNU601 and MKN74 knock-in cells were used for analysis of ERH function. RESULTS: ERH was overexpressed in stomach cancer tissues compared with normal tissues according to proteomics analysis (n=29, P<0.01) of patient samples. Based on IHC, patients with tumors overexpressing ERH had lower T stage and lower TNM stage classifications, lower cancer recurrence rates and longer survival times than did patients with tumors showing low expression of ERH (P=0.04). In vitro, forced expression of ERH significantly decreased GC cell migration and invasion, and depletion of ERH triggered GC cell migration and invasion but had no effect on proliferation in vitro. CONCLUSIONS: The findings from the present study show that ERH is associated with decreased cancer cell migration and invasion, suggesting that overexpression of ERH may serve as a marker of good prognosis for patients with GC.

Characteristics of Gastric Carcinomas With High ERCC1 Expression and the Prognostic Value of ERCC1 Expression.

BACKGROUND/AIM: We aimed to evaluate the characteristics of gastric carcinoma with high excision repair cross complementing 1 (ERCC1) expression and the prognostic value of ERCC1 expression. MATERIALS AND METHODS: ERCC1 expression was evaluated by immunohistochemistry in 309 surgically resected gastric carcinoma specimens using a tissue microarray. Cancer-related survival was analysed using competing risk analysis. RESULTS: Compared to ERCC1-low gastric carcinomas, ERCC1-high gastric carcinomas showed less local invasion (p=0.0013), lower N stage (p=0.0302), earlier pTNM stage (p=0.0003), and less frequent recurrence (p=0002). Patients with ERCC1-high gastric carcinoma showed lower cumulative incidence function estimate of cancer-related death [3.37; 95% confidence intervaI (CI)=0.89-8.75] than did those with ERCC1-low gastric carcinoma (17.12; 95% CI=12.24-22.69; p-value by Gray's test=0.0012). Adjusted proportional sub-distribution hazard ratio for cancer-related death in the patients with ERCC1-high tumour was 0.272 (95% CI=0.084-0.878; p=0.0295). CONCLUSION: High ERCC1 expression may be an independent positive prognostic marker for gastric carcinoma.

PRDX4 overexpression is associated with poor prognosis in gastric cancer.

Peroxiredoxin IV (PRDX4) is a multifunctional protein that is involved in cell protection against oxidative injury, regulation of cell proliferation, modulation of intracellular signaling, and the pathogenesis of tumors. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer. The aim of the present study was to investigate whether PRDX4 could be a marker of poor prognosis in patients with gastric cancer. Immunohistochemistry was used to validate PRDX4 as a prognostic marker for gastric cancer. Short hairpin RNA (shRNA)-mediated knockdown of PRDX4 expression in AGS cells and MKN28 cells was used for functional studies, and PRDX4 overexpression in PRDX4-depleted cells was used for knock-in studies. Based on immunohistochemistry data, TNM stage and PRDX4 were independent prognostic factors in the Cox proportional hazard model (P<0.05). In the survival analysis, the PRDX4-overexpressing group demonstrated significantly worse survival than the PRDX4-underexpression group (P<0.01). In vitro, knockdown of PRDX4 expression by shRNA caused a significant decrease in cancer invasion. Conversely, overexpression of PRDX4 in PRDX4-depleted cancer cells promoted migration and invasion. By measuring the expression of EMT-related genes, we found that E-cadherin was increased in shPRDX4 cells compared with control shMKN28 cells, and snail and slug were decreased in shPRDX4-1 cells compared with sh-control cells. Furthermore, the expression levels of these genes could be recovered in rescue experiments. In conclusion, the results of the present study suggested that PRDX4 is a marker of poor prognosis in gastric cancer and that PRDX4 is associated with cancer cell migration and invasion via EMT.

Nomogram for predicting gastric cancer recurrence using biomarker gene expression.

BACKGROUND: Recently, researchers have tried to predict patient prognosis using biomarker expression in cancer patients. The aim of this study was to develop a nomogram predicting the 5-year recurrence-free probability (RFP) of gastric cancer patients using prognostic biomarker gene expression. METHODS: We enrolled 360 patients in the training data set to develop the predictive model and nomogram. We analyzed the patients' general variables and the gene expression levels of 10 prognostic biomarker candidates between the nonrecurrence and recurrence groups. We also performed external validation using 420 patients from the validation data set. RESULTS: The final nomogram was composed of age, sex, and the expression levels of CAPZA, PPase, OCT-1, PRDX4, gamma-enolase, and c-Myc. The five-year RFPs were 89%, 75%, 54% and 32% for the patients in the low-risk, intermediate-risk, high-risk and very-high-risk groups in the development cohort, respectively. In the external validation cohort, the 5-year RFPs were 89%, 75%, 63% and 60%, respectively. The areas under the curve were 0.718 (95% CI, 0.65-0.78) and 0.640 (95% CI, 0.57-0.70) for the training and validation data sets, respectively. The RFP Kaplan-Meier curves were significantly different among the 4 groups in the training and validation data sets (p < 0.0001). CONCLUSION: This newly developed nomogram using gene expression can predict the 5-year RFP for gastric cancer patients after surgical treatment. We hope that this nomogram will help in the therapeutic decision between endoscopic treatment and gastrectomy.

Prognostic role of S100A9 expression in patients with clear cell renal cell carcinoma.

S100A9 was originally regarded as a regulator of immune response and a mediator of the inflammatory process. Recent studies have suggested that S100A9 expression plays an important role during tumor development, progression and metastasis in various cancers. The present study aimed to investigate the expression and prognostic role of S100A9 in clear cell renal cell carcinoma (ccRCC).S100A9 expression was examined by immunohistochemical staining in 152 patients who underwent surgical resection due to ccRCC. The correlation between S100A9 expression and clinicopathological data and its prognostic role were evaluated in patients with ccRCC.S100A9 revealed high expression in 37 cores (12.6%) of ccRCC. S100A9 expression was significantly associated with T stage (P < .001) and Fuhrman nuclear grade (P < .001), but not with patient age (P = .821) and sex (P = .317). Survival analysis revealed that high S100A9 expression is an independent factor for unfavorable disease-free survival (hazard ratio, 2.423; 95% confidence interval, 1.044-5.621; P = .039) and disease-specific survival (hazard ratio, 2.428; 95% confidence interval, 1.130-5.214; P = .023) in patients with ccRCC.S100A9 expression can be a useful prognostic factor in patients with ccRCC.

Identification of Myoferlin Expression for Prediction of Subsequent Primary Malignancy in Patients With Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: Multiple primary malignant tumors are common in patients with renal cell carcinoma. However, reports on the factors that can identify patients with a risk for subsequent primary malignancies have been lacking. This study aimed to investigate whether myoferlin expression can be used as a potential marker to predict subsequent primary malignancies in patients with clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: We evaluated the relationship of subsequent primary malignancies with clinicopathological factors and myoferlin expression in 152 patients with ccRCC, and we analyzed the strength of the association with myoferlin expression. RESULTS: The development of subsequent primary malignancies exhibited significant correlation with patient age (p=0.029), sex (p=0.015), T stage (p<0.001), and myoferlin expression (p=0.017). Furthermore, myoferlin hyperexpression was determined as an independent risk factor for developing a subsequent primary malignant tumor in patients with ccRCC (odds ratio(OR), 2.485, 95% Confidence Interval(CI)=1.052-5.870, p=0.038). CONCLUSION: Myoferlin hyperexpression can be a useful marker for predicting the development of subsequent primary malignancies in patients with ccRCC.

The Use of CD44 Variant 9 and Ki-67 Combination Can Predicts Prognosis Better Than Their Single Use in Early Gastric Cancer.

PURPOSE: We previously demonstrated that CD44v9 and Ki-67 played an important role in predicting poor prognosis of early gastric cancer (EGC). However, little is known about combined use of both biomarkers as prognostic biomarker. The present study was performed to investigate the significance of CD44v9 and Ki-67 expression as a combination biomarker for EGC. MATERIALS AND METHODS: With tissue microarray for 158 EGC tissues, we performed immunohistochemical staining for CD44v9 and Ki-67. The whole patients were divided into three groups (group A, CD44v9- negative/Ki-67-low; group B, neither group A or C; and group C, CD44v9-positive/Ki-67- high). Its clinical significance was re-analyzed with adjustment via propensity score matching (PSM). For validation, we performed bootstrap resampling. RESULTS: The median follow-up duration was 90.4 months (range, 3.7 to 120.4 months). In the comparison according to CD44v9/Ki-67 expression, the combined use of the two biomarker clearly separated the three groups by 5-year survival rates (5-YSR, 96.3%, 89.8%, and 76.8% in group A, B, and C, respectively; p=0.009). After PSM, 5-YSR were 97.7% and 76.8% in group A+B and group C, respectively (p=0.002). Multivariable analysis demonstrated that group C had independently poor prognosis (hazard ratio, 9.137; 95% confidence interval, 1.187 to 70.366; p=0.034) compared with group A. Bootstrap resampling internally validated this result (p=0.016). CONCLUSION: This study suggests that both positive CD44v9 and high Ki-67 expression are associated with poor prognosis in EGC, and the combined use of these markers provides better prognostic stratification than the single use of them.