Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis.

BACKGROUND: This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC). METHODS AND RESULTS: The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients. To confirm the findings in-vitro, 5FU-resistant HT29 cells were generated by subjecting HT-29 cells to the increasing concentrations of 5FU for 6 months. The 5FU resistance was observed in WST-1 and Annexin V analyses. The colony formation and wound healing assays were assessed to determine the metastatic properties of the cells. Expression levels of LncRNAs and mRNA of EMT-related genes were determined by RT-PCR. The role of LncRNA on metastasis and 5FU sensitivity were confirmed in pcDNA3.0-PTENP1 and si-MALAT1 expressed 5FU-resistant HT29 cell lineages. RESULTS: High MALAT1 (p = 0.0002) and low PTENP1 (p = 0.0044) expressions were significantly associated with 5-FU resistance and tumor relapse in stage I/II CC. The invasiveness and colony-forming characteristics of 5-FU-resistant cell lineages were higher as compared to the parent HT-29. Moreover, the expression of MALAT1 (p = 0.0009) was increased while the expression of PTENP1 (p = 0.0158) decreased in 5FU-resistant-HT-29 cells. Si-MALAT1 treatment increased cell sensitivity to 5FU, whereas it decreased invasive behaviors of 5 FU-resistant-HT-29 cells. CONCLUSION: MALAT1 may be a biomarker in predicting recurrence in early-stage CC. Our findings suggest that a cell-based therapy to target MALAT1 could be established for these patients to prevent metastasis and 5-FU resistance.

Thymic tumors and results of radiotherapy.

AIM: The aim of this study was to evaluate thymic epithelial tumors (TETs) for treatment outcomes and prognostic factors on survival. BACKGROUND: TETs are very rare neoplasms and multidisciplinary approach is recommended according to prognostic factors. MATERIALS AND METHODS: Between 1995 and 2013, 31 patients were treated with median 5400 cGy (range: 1620-6596 cGy) radiotherapy (RT). Eleven patients received adjuvant or concurrent chemotherapy. There were 25 thymomas, 4 thymic carcinomas and 2 thymic neuroendocrin carcinomas. According to Masaoka, staging and WHO classification, cases were divided to good (n: 10), moderate (n: 9) and poor (n: 12) prognostic risk groups. Survival was calculated from diagnosis. RESULTS: In January 2016, 22 cases were alive with median 51.5 months (range: 2-170.5) follow-up. Recurrences were observed in 29% of patients in median 29.5 months (range: 6.5-105). Local control, mean overall (OS) and disease-free survival (DFS) rates were 86%, 119 and 116 months, respectively. There was a significant difference for R0 vs. R+ resection (81% vs. 43%, p = 0.06, and 69% vs. 46%, p = 0.05), Masaoka stage I-II vs. III-IV (75% vs. 52%, p = 0.001, and 75% vs. 37%, p < 0.001), and also prognostic risk groups (100% vs. 89% vs. 48%, p = 0.003, and 100% vs. 87% vs. 27%, p = 0.004) in terms of 5-year OS and DFS, respectively. CONCLUSION: In our study, prognostic risk stratification was shown to be a significant predictor of survival. There is a need to investigate subgroups that may or may not benefit from adjuvant RT.

Impact of 3'UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population.

OBJECTIVE: Several studies have demonstrated the importance of mutations in codons 12, 13 and 61 and variations in the 3' untranslated region (3'UTR) of the KRAS gene, frequently observed genetic events in the progression of pancreatobiliary tumors (PBT). However, limited data exist on the clinical effect of these alterations. The aim of the current study was to clarify the frequency of relevant alterations of the 3'UTR regions of the KRAS gene and the effect of KRAS 3'UTR polymorphisms on the prognosis of patients with codon 12, 13 and 61 mutations in a Turkish population with PBT. METHODS: Codons 12, 13, and 61 and 3'UTRs of the KRAS gene were screened by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing in 43 patients and 10 controls. Chi-squared and independent sample T tests were used to evaluate the results of the mutation analysis and clinical features of the patients. RESULTS: We defined the c.38G > A (rs112445441, p.G13D) (39.54%) mutation and two 3'UTR variations, c.*4066delA (rs560890523) (23.26%) and c.*4065_*4066delAA (rs57698689) (6.98%), in the KRAS gene of Turkish patients. There was a statistically significant relationship between the c.*4066delA (rs560890523) and c.*4065_*4066delAA (rs57698689) variations and invasion and lymph node metastasis status of the patients (p < 0.001). Compared to patients with c.38G > A (rs112445441, p.G13D), patients with c.*4066delA (rs560890523) and c.38G > A (rs112445441, p.G13D) presented more aggressive tumors with highly invasive features. The present study contributes findings regarding the clinical effects of KRAS alterations in PBT. Based on our study, further investigations are required.

Can heat shock protein 32 be used for the early diagnosis of acute mesenteric ischemia?

OBJECTIVE: Acute mesenteric ischemia is a challenging and fatal disease. The aim of this study was to detect the heat shock protein 32 (HSP32) response in intestinal tissue and systemic blood to intestinal ischemia and ischemia/reperfusion to define a tool for the early diagnosis of acute mesenteric ischemia. MATERIAL AND METHODS: Thirty female Wistar albino rats were equally divided into 3 groups. Group 1 rats underwent simple laparotomy and closure (control). In Group 2 rats, 1-hour intestinal ischemia followed by 5-hour reperfusion was performed, and Group 3 rats were subjected to 6-hour intestinal ischemia. The experiment was repeated with a 24-hour waiting period. At the end of the waiting period, blood was withdrawn from the tail veins of the rats and the rats were sacrificed via cardiac puncture. Re-laparotomy was subsequently performed and intestinal tissue and luminal samples were obtained for biochemical and pathological investigations. The HSP32 levels of intestinal tissues, luminal contents and blood levels were compared among the groups. RESULTS: At the end of the 24-hour waiting period, the median tissue HSP32 levels were 0.43 (0-6.6) ng/mL for Group 1, 9.51 (2.5-49.9) ng/mL for Group 2 and 43.13 (6.3-121.3) ng/mL for Group 3 (p=0.001). The median blood HSP32 levels were 0.11 (0.1-1.4) ng/mL for Group 1, 0.42 (0.1-0.7) ng/mL for Group 2, and 0.25 (0.1-1.2) ng/mL for Group 3 (p=0.047). The HSP levels in the luminal contents were undetectable. CONCLUSION: Both ischemia and ischemia/reperfusion significantly raised intestinal tissue HSP32 levels in comparison with the control group. However, this change was not reflected in the circulating blood or luminal contents.

MicroRNA expression patterns of tumors in early-onset colorectal cancer patients.

BACKGROUND: The expression of microRNAs (miRNAs) may differ in tumors from patients with different ethnic origins and ages. The aims of the present study were to clarify the appropriate alterations of miRNA expression associated with the early stages of carcinogenesis in early-onset Turkish colorectal cancer (CRC) patients and to define specific biomarkers that could be used as new diagnostic and prognostic markers for this population. MATERIALS AND METHODS: The expression profiles of 38 different miRNAs associated with CRC were evaluated using miRNA polymerase chain reaction arrays in tumors and surgical margin tissue samples from 40 sporadic early-onset Turkish CRC patients. The relationships between the miRNA expression profiles and the characteristics of the tumors and patients were evaluated. RESULTS: The expression of miR-106a was found to be upregulated, and miR-143 and miR-125b levels were found to be downregulated in tumor tissues compared with the normal tissues. The high expression level of miR-106a (2.93-fold; P = 0.031) and low expression level of miR-125b (2.42-fold; P = 0.063) were observed in tumors with lymph node metastases compared with the normal colorectal mucosa samples. However, the deregulation of these miRNAs was not significantly associated with survival (log-rank P > 0.05). CONCLUSIONS: The present results implied that miR-106a and the miR-125b were associated with the formation and invasion of colorectal tumors. Thus, these miRNAs might be used as significant prognostic factors and indicators of early-stage CRC. Further studies and validations are required; these miRNAs may provide novel molecular targets for CRC treatment.

Microscopic Growth Pattern of Metastatic Colorectal Carcinomas, Morphological Findings of the Non-Neoplastic Liver, and Their Relationship With Prognosis and Survival.

Introduction. Various clinicopathological, radiological, and molecular parameters are predictive of prognosis in patients with colorectal carcinoma and distant organ metastases continue to have a significant place among them. Recent studies reveal that not only the presence of metastases but also the histopathological growth pattern of the metastatic tumor significantly affects prognosis. This study aimed to investigate the prognostic significance of the histopathological growth patterns of metastatic tumors, the morphological findings in the peritumoral non-neoplastic liver, and its relationship with survival in patients who have metastatic colorectal carcinoma. Materials and Method. Hematoxylin and eosin-stained slides of the tumors were re-examined in terms of histopathological diagnosis, growth pattern, presence and degree of peritumoral lymphocytic infiltration, steatosis, cholestasis, and peritumoral ductular reaction in the non-neoplastic liver. Results. In terms of histopathological growth patterns, 24 (47%) tumors showed replacement, 19 (37%) showed desmoplastic and 8 (16%) showed pushing growth pattern. In terms of total survival, there was a significant difference (P = .011) between desmoplastic and replacement growth patterns, and the survival period was shorter in patients with replacement growth patterns. Conclusion. Recent studies show that histopathological growth patterns in metastatic liver tumors may be a promising prognostic and predictive parameter. It is important to include this parameter in the pathology reports as it does not require additional equipment for evaluation in routine pathology practice, does not bring additional costs, or takes a long time to evaluate. This feature can be evaluated standardly by every pathologist.

Microsatellite instability status affects gene expression profiles in early onset colorectal cancer patients.

BACKGROUND: The association between microsatellite instability (MSI) status and gene expression profiles in the early onset sporadic colorectal cancer (CRC) has not been clearly established. The aim of this study was to identify the altered gene expression patterns depending on the MSI status of early onset CRC and determine specific biomarkers that could provide novel therapeutic molecular targets in the Turkish population. MATERIALS AND METHODS: MSI markers (BAT25, BAT26, D2S123, D5S346, and D17S250) were investigated in tumors from 36 early onset sporadic CRC patients in whom gene expression profiles were analyzed previously. The relationship between the gene expression profiles depending on MSI status was evaluated. RESULTS: A total of 15 tumors (16.66%) were identified as having MSI and 21 tumors (58.33%) were identified as having microsatellite stability (MSS). CK20 and MAP3K8 upregulation, observed in MSS tumors, was significantly associated with lymph node metastasis, recurrence, and/or distant metastasis and a short median survival (P < 0.05). REG1A upregulation is also correlated with recurrence and/or distant metastasis and a short median survival in patients with MSI tumors (P < 0.05). CONCLUSIONS: High expression levels of CK20 and MAP3K8 in MSS tumors and REG1A in MSI tumors correlated with a poor prognosis in CRC patients. Further studies and validations are required; these genes may provide novel therapeutic molecular targets for the development of anticancer drugs related to MSI status for early onset CRC treatment.

Somatostatin receptor 1 (SSTR1) and somatostatin receptor 5 (SSTR5)expression in hepatocellular carcinoma.

BACKGROUND/AIMS: Somatostatin analogues are considered for the treatment of advanced hepatocellular carcinomas which express somatostatin receptors (SSTR). There is limited data for the SSTR subtypes. Somatostatin receptor 1 (SSTR1) and Somatostatin receptor 5 (SSTR5) expressions are investigated in needle biopsy materials of patients diagnosed as hepatocellular carcinoma, using immunohistochemical methods in the assistance of antibody kits. METHODOLOGY: The needle biopsy materials of forty-one patients that were diagnosed as hepatocellular carcinoma between 2000 and 2006 have been examined. The underlying diseases, 4FP values, treatments received and the sections were evaluated after SSTR1 and SSTR5 staining. RESULTS: SSTR1 expression was found in 31 (75.6%) and SSTR5 expression in 21 of (51.2%) 41 biopsies. SSTR1 and SSTR5 expressions were not determined in 10 (24.4%) and 20 (48.8%) of the cases. In addition, no significant correlation of the SSTR1 and SSTR5 stains with the underlying diseases (chronic hepatitis and cirrhosis) and gender was observed. CONCLUSIONS: This study demonstrated that the tumor cells in the tissue samples of the patients diagnosed with advanced-stage hepatocellular carcinoma expressed a high proportion of SSTR1 and SSTR5.

Liver metastasis of breast carcinoma: An unusual presentation and growth pattern.

Breast carcinoma is one of the tumors that frequently metastasize to the liver. Extramedullary hematopoiesis (EMH) usually occurs due to insufficient medullary hematopoiesis. In this case report, we present a female patient with sinusoidal breast carcinoma metastasis and extramedullary hematopoiesis in liver biopsy. A 63-year-old female patient with history of breast carcinoma was admitted to our center with respiratory distress. Pleural effusion was detected and thoracentesis was planned. Treatment was given after detection of non-mycobacterial tuberculosis bacillus in the thoracentesis fluid. Antibiotherapy was terminated due to elevation of liver enzymes and bilirubin. The patient's clinical status was evaluated and treatment was re-initiated. The patient did not have any mass lesion in the liver. Tru-cut biopsy was performed to evaluate a possible tuberculosis involvement in the liver. The diagnosis of metastatic breast carcinoma located in the sinusoidal area and cholestatic liver with extramedullary hematopoiesis foci was given using the histomorphological, immunohistochemical and histochemical findings. Radiological evaluation has an important role in staging of malignancies. However, it should be kept in mind that hepatic metastases may present without formation of a mass lesion, and unexpected laboratory results of cases without abnormal radiological features should raise the suspicion of a metastasis. Such materials should be evaluated in detail by making multiple serial sections in the pathology laboratory. Rare metastatic tumor growth patterns not causing a mass lesion such as sinusoidal or portal pattern, should also be kept in mind.

IgG4-Related Disease of the Ovary.

Immunoglobulin G4-related disease is characterized by dense fibrosis, obliterative phlebitis, and lymphoplasmacytic infiltration that contains abundant IgG4 positive plasma cells. It causes tumefactive lesions in the involved organs and is most commonly seen in the salivary glands, pancreas, and retroperitoneum. Ovarian involvement has been reported in only two cases. In our case, a 58-year-old female patient presented with abdominal distention and pain. Pelvic computed tomography revealed a soft tissue lesion compatible with the omental cake, several intraabdominal implants, and bilateral adnexal fullness. A laparotomy was performed under suspicion of peritoneal carcinomatosis secondary to bilateral adnexal mass. In the histopathologic examination, abundant lymphoplasmacytic infiltration and dense fibrosis were observed in both ovaries and the peritoneum. In the areas of greatest density, the density of IgG4-positive plasma cells was found to range from 40 to 50 per high-power field. The patient was accepted as suffering from probable IgG4-related disease because of the bilateral involvement of the ovaries and the histopathological findings. In conclusion, we present this case to draw attention to the fact that IgG4-related disease can also be seen in the ovary.

Do morphologic characteristics play a role in nodal metastatic progression of well-differentiated pancreatic neuroendocrine tumors?

BACKGROUND: Pancreatic neuroendocrine neoplasms (NENs) are tumors with histopathologic and prognostic heterogeneity that pose difficulties in establishing standards for diagnosis, classification, and treatment. Among NENs, well-differentiated neuroendocrine tumors (NETs) have been classified as grade 1, 2, and 3 in the most recently released World Health Organization classification. Although well-differentiated NETs are associated with relatively better prognosis, they have a potential for malignant behavior such as extrapancreatic spread, metastasis, or recurrence. The present study aimed to evaluate clinical and histomorphologic findings of patients with well-differentiated pancreatic NETs and to identify histopathologic findings effective in predicting nodal metastatic progression. METHODS: The study group consisted of 54 patients diagnosed with well-differentiated NET. All preparations and blocks of the patients were examined for the following histopathologic parameters: tumor diameter, microscopic tumor growth pattern (solid, trabecular, acinar, and mixed), cellular features (clear, eosinophilic, oncocytic, peliotic, and pseudopapillary), stromal changes (calcification, lymphocytic infiltration, and stromal hyalinization), presence of necrosis, perineural invasion, lymphovascular invasion, mitotic activity, and Ki67 proliferative index. RESULTS: Lymph node metastasis was present in 7 patients. Lymph node metastasis was significantly associated with tumor diameter of >2 cm (p = 0.012), Ki67 proliferative index of >20% (p = 0.022), grade 3 tumors (p = 0.002), presence of dense stromal hyalinization (p = 0.034), and mild lymphocytic infiltration (p = 0.041). CONCLUSION: The present study revealed that the new findings such as presence of dense stromal hyalinization and absence of remarkable lymphocytic infiltration could be predictive morphologic findings for the development of lymph node metastasis.

Maspin expression in gastrointestinal stromal tumors.

BACKGROUND: To investigate the role of maspin expression in the progression of gastrointestinal stromal tumors, and its value as a prognostic indicator. METHODS: In the study 54 patients with GIST diagnosis were included in Uludag University of Faculty of Medicine, Department of Pathology between 1997-2007. The expression of maspin in 54 cases of gastrointestinal stromal tumor was detected by immunohistochemistry and compared with the clinicopathologic tumor parameters. RESULTS: The positive expression rates for maspin in the GISTs were 66.6% (36 of 54 cases). Maspin overexpression was detected in 9 of 29 high risk tumors (31%) and was significantly higher in very low/low (78.6%) and intermediate-risk tumors (63.6%) than high-risk tumors. CONCLUSIONS: Maspin expression might be an important factor in tumor progression and patient prognosis in GIST. In the future, larger series may be studied to examine the prognostic significance of maspin in GISTs and, of course, maspin expression may be studied in different mesenchymal tumors.

Elevated serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) in patients with nonalcoholic steatohepatitis and chronic hepatitis C.

BACKGROUND: Caspase-cleaved cytokeratin 18 (CK18-Asp396) is released from hepatocytes during apoptosis. Recent studies have indicated that serum levels of CK18-Asp396 could be a clinically useful biomarker of chronic liver disease. To shed more light on the rate of hepatocyte loss by apoptosis in chronic liver disease, serum levels of CK18-Asp396 were examined in patients with nonalcoholic steatohepatitis (NASH) and chronic hepatitis C. MATERIAL/METHODS: Apoptotic CK18-Asp396 levels were quantified in sera from 35 patients with nonalcoholic steatohepatitis (NASH), 21 patients with chronic hepatitis C (HCV), and 18 healthy controls. RESULTS: Analysis of serum CK18-Asp396 levels showed an increasing trend starting from healthy controls (median: 54.5 U/l), to HCV patients (80.1 U/l), to patients with NASH (144.1 U/l, Kruskall-Wallis test: P<0.001). Post hoc analyses revealed that CK18-Asp396 levels were significantly higher in the NASH patients than in both HCV patients (P=0.008) and healthy controls (P<0.001). Moreover, the levels were significantly higher in patients with HCV than in control individuals (P<0.05). In patients with chronic HCV infection there was a significant positive correlation between serum CK18-Asp396 levels and AST (r=0.442, P<0.05), the ultrasonographic grade of steatosis (r=0.446, P<0.05), and the histological steatosis score (r=0.759, P<0.001). CONCLUSIONS: Although subject to future confirmation, these pilot findings seem to indicate that serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) are higher in patients with NASH than in those with chronic HCV infection. These data suggest that NASH patients have an increased hepatocyte loss by apoptosis compared with chronic hepatitis C patients.

P53 expression in synchronous colorectal cancer.

OBJECTIVE: We reviewed cases of primary colorectal adenocarcinoma to document synchronous colon and rectum adenocarcinoma (SCRC). METHODS: In a retrospective setting, 764 cases underwent surgical resection for primary colorectal adenocarcinoma and referred to the Department of Surgical Pathology, Uludag University, Medical Faculty for diagnoses between 1997 and 2006, were reviewed. Tumor site, depth of invasion, coexistence of adenoma, distance between these multiple primary tumors, degree of p53 expression, and p53 expression pattern indicating polyclonal or monoclonal origins were noted in order to establish a possible effect on prognosis. RESULTS: There were 28 cases with SCRC of colon and rectum. Nine cases were female, 19 cases were male (female to male ratio was 1:2). Most of the cases were within the 5th and the 6th decades. There were statistically significant relationships between p53 expression and differentiation status (p=0.001), and invasion depth (p=0.03). Forty of 62 colorectal carcinomas showed immunohistochemical positivity for p53. Six cases showed a discordant pattern of p53 mutation among individual lesions indicating polyclonal origin. CONCLUSION: Synchronous colon and rectum adenocarcinoma is not rare. The incidence is 3.6% in our series. We believe that further studies with larger series are needed for p53 to prove useful in predicting prognosis of SCRCs and assessing the polyclonal origin of SCRC at a genetic level.

Perforation of the small intestine caused by enteropathy-associated T cell lymphoma.

Enteropathy-associated T cell lymphoma is a rare lymphoma specific to the gastrointestinal system, arising from intraepithelial T lymphocytes, that is often associated with celiac disease. We report a 53-year-old female patient with no previous disease who presented with severe abdominal pain. Physical examination revealed diffuse abdominal tenderness and abdominal guarding and the patient underwent emergency surgery with a diagnosis of acute abdomen. During the operation, a 20-cm mass was found located on Treitz ligament, invading the duodenum and pancreatic head and perforating the jejunum. Histologically, medium-sized monomorphic atypical lymphocyte infiltration with dark nucleus and narrow cytoplasm was seen in the layers of mucosa, submucosa, muscular wall, and serosa of the duodenum. The final pathological diagnosis was "enteropathy-associated T cell lymphoma type 2" based on immunohistochemical and serological findings. Based on the World Health Organization 2008 criteria, enteropathy-associated T cell lymphoma has two subtypes. Type 1 enteropathy-associated T cell lymphoma is associated with celiac disease and has HLA DQ2 and HLA DQ8 genotype. Enteropathy-associated T cell lymphoma 2 enteropathy-associated T cell lymphoma seldom occurs and is not associated with celiac disease.

Coexistence of gastric multiple neuroendocrine tumors with unusual morphological features and gastric signet-ring cell carcinoma.

The coexistence of signet-ring cell carcinoma and neuroendocrine tumors is very rare. We report a 57-year-old man who presented with a history of weight loss and nausea. Gastric mucosal biopsies obtained during gastrointestinal endoscopy revealed a gastric signet-ring cell carcinoma. The patient underwent a total gastrectomy with a standard D2 lymph node dissection. Ten individual tumors were detected in the resected specimen. Based on the histopathological and immunohistochemical findings, the final diagnosis was co-existing signet-ring cell carcinoma and neuroendocrine tumor. Spindle-shaped cells and extracytoplasmic mucin were noted in some tumor cells forming the neuroendocrine component. This case is a rare synchronous tumor because of its unusual neuroendocrine component.

Overexpression of the Long Noncoding RNA HomeoboxA Transcript at the Distal Tip Predicts Poor Prognosis in a KRAS-Independent Manner in Periampullary Region Tumors.

OBJECTIVES: Periampullary region tumors (PRTs) are the fifth highest cause of cancer-related deaths worldwide. Although recent studies have highlighted the prognostic value of the long noncoding RNA HomeoboxA transcript at the distal tip (HOTTIP) in patients with pancreatic ductal adenocarcinoma, the relationship between HOTTIP and clinical outcome of all PRTs remains obscure. The aim of this study was to clarify the prognostic significance of HOTTIP in patients with all PRTs related to KRAS mutational status. METHODS: HomeoboxA transcript at the distal tip expression was detected in 100 PRT samples using quantitative real-time polymerase chain reaction. The associations between HOTTIP levels, clinicopathological factors, and patient prognosis were also analyzed. RESULTS: The expression of HOTTIP was found to be significantly upregulated by 32-fold (P = 0.031) in tumor tissues compared with normal tissues. The over expression of HOTTIP was related with presence of invasion and metastasis (P = 0.0467, P = 0.0256). In addition, increased HOTTIP expression was associated with poor prognosis independent of KRAS mutation (P < 0.001; n = 72). Moreover, multivariate analysis showed that high HOTTIP expression was an unfavorable prognostic factor for overall survival. CONCLUSIONS: Our findings indicate that high levels of HOTTIP expression have the potential to be an independent, unfavorable prognostic factor for patients with PRT.

Coexistence of MACC1 and NM23-H1 dysregulation and tumor budding promise early prognostic evidence for recurrence risk of early-stage colon cancer.

The tumor-node-metastasis (TNM) classification, the presence of a mucinous component, and signet ring cells are well-known criteria for identifying patients at a high risk for recurrence and determining the therapeutic approach for early-stage colon cancer (eCC). Nevertheless, recurrence can unexpectedly occur in some eCC cases after surgical resection. The aims of the present study were to evaluate the relation of dysregulated MACC1, c-MET, and NM23-H1 expression with the histopathological features of tumors in recurrence formation in eCC cases. A total of 100 sporadic eCC patients without poor prognosis factors were evaluated in this study. The relationship between the altered expression of MACC1, c-MET, and NM23-H1 and pathological microenvironmental features, including the presence of tumor budding and desmoplasia, were assessed. The primary outcomes, including 5-year overall survival (OS) and disease-free survival (DFS), were also measured. Compared with nonrecurrent patients, the expression level of MACC1 was 8.27-fold higher, and NM23-H1 was 11.36-fold lower in patients with recurrence during the 5-year follow-up (p = 0.0345 and p = 0.0301, respectively). In addition, the coexistence of high MACC1 and low NM23-H1 expression and tumor budding was associated with short OS (p < 0.001). We suggest that the combination of reduced NM23-H1, induced MACC1, and the presence of tumor budding are promising biomarkers for the prediction of recurrence and may aid the stratification of patients with stage II colon cancer for adjuvant chemotherapy.

Clinical significance of activity of ALT enzyme in patients with hepatitis C virus.

AIM: To investigate serum alanine aminotransferase (ALT) levels in relation to the clinical, biochemical, ultrasonographic and histological characteristics of patients with hepatitis C virus. METHODS: Duration of disease, HCV-RNA, liver steatosis, and the hepatitis activity index (HAI) were correlated with serum ALT in 36 patients with HCV. ALT values were also investigated in 16 control subjects without any liver diseases. RESULTS: In bivariate analyses, ALT levels correlated with duration of HCV infection (P < 0.01), HCV-RNA (P < 0.05), and the HAI (P < 0.01). Among the components of the HAI, ALT concentrations were significantly associated with periportal bridging/necrosis (P < 0.01) and fibrosis (P < 0.05). In multivariate analysis, periportal bridging/necrosis (beta = 0.508; P < 0.01), duration of HCV infection (beta = 0.413; P < 0.01), and HCV-RNA (beta = 0.253; P < 0.05) were independently associated with ALT activity. The normal ALT activity for men and women was < 23 IU/L and < 22 IU/L, respectively. CONCLUSION: In patients with HCV, alterations in the liver tissue as reflected by ALT elevation are mainly associated with periportal bridging/necrosis, viral load and duration of disease. A cut-off value < 23 IU/L distinguished with high diagnostic accuracy healthy controls from patients with HCV.

Significance of p53 expression in gastrointestinal stromal tumors.

BACKGROUND/AIMS: Gastrointestinal stromal tumors are non-epithelial tumors originating from the gastrointestinal tract walls. They expose a wide spectrum of histological properties from benign to poorly differentiated malignant tumors. METHODOLOGY: In this study 41 cases of gastrointestinal stromal tumors were reviewed for p53 expression using immunohistochemical stains. Immunoreactivity properties of the tumors were compared to prognostic factors such as mitotic index, tumor size, tumor site, presence of necrosis, mucosal invasion, proliferative index, telomerase activity, hemorrhage, cellularity, and histological pattern. RESULTS: There was a significant difference in positive immunostaining of three case groups (12.2% in benign, 19.5% in borderline, and 68.3% in malignant group). Statistical analysis revealed a statistically significant positive correlation between p53 immunostaining properties and tumor size (p = 0.01), mitotic index (p=0.05), cellularity (p = 0.042), and diagnosis (p = 0.01). CONCLUSIONS: We conclude that p53 expression may be a useful tool in classifying and predicting the prognosis of gastrointestinal stromal tumors as it is well correlated with tumor size, mitotic index, cellularity, and diagnosis according to our study results.