Prognostic value of NOTCH1 and OCT4 in gastric carcinoma.

Background: NOTCH1 pathway activation has been recently described to be a key player in gastric carcinogenesis, enhance the survival and proliferation of cancer stem cells (CSCs) and mediate chemoresistance in several malignancies. Aim: This study investigated the correlation between NOTCH1 and CSC marker OCT4 (octamer binding transcription factor-4) expression and the clinicopathological properties, survival and treatment outcome in patients with gastric carcinoma (GC) receiving adjuvant chemotherapy. Materials and. Methods: NOTCH1 and OCT4 were immunohistochemically detected in 50 post-operated specimens of GC. Patients' data regarding disease-free survival (DFS), overall survival (OS), and the response to the chemotherapy was statistically analyzed. Results: NOTCH1 and OCT4 overexpression was detected in 60% and 52% of GC tissues, respectively, and that was significantly higher than the rates in adjacent non-neoplastic gastric mucosa (P < 0.05). A significant correlation was detected between overexpression of NOTCH1 and OCT4 in GC and aggressive clinicopathological features; poor differentiation (P = 0.021, P = 0.037, respectively), depth of tumor invasion (P < 0.001 for both), TNM stage (P < 0.001 for both), lymph node metastasis (P = 0.002, P = 0.003, respectively) and distant metastasis (P < 0.001 for both). NOTCH1 was positively correlated with OCT4 (P = 0.002). Survival analysis disclosed that upregulation of NOTCH1 and OCT4 was associated with worse DFS (P = 0.013, P < 0.001, respectively) and OS (P < 0.001 for both). Overexpression of NOTCH1 and OCT4 correlated with poor response to chemotherapy (P = 0.013, P = 0.005, respectively) and worse clinical outcome. Conclusion: Combined detection of these proteins might disclose even better predictive value for shorter survival and resistance to chemotherapy.

ERCC1, PARP-1, and AQP1 as predictive biomarkers in colon cancer patients receiving adjuvant chemotherapy.

BACKGROUND: The recognition of high-risk colon cancer patients prone to chemoresistant and recurrent disease is a challenge. OBJECTIVES: We aimed to assess the immunohistochemical expression of ERCC1, PARP-1, and AQP1 in 60 cases of stage II and III colon cancer who underwent curative resection and adjuvant chemotherapy. Their predictive role of tumor progression and disease-free survival (DFS) was analyzed. METHODS: The immunohistochemical expression of ERCC1, PARP-1, and AQP1 in 60 cases of stage II and III colon cancer who underwent curative resection and adjuvant chemotherapy was studied. The collected data on the overall survival (OS), disease-free survival (DFS), and the response to the chemotherapy were analyzed. RESULTS: Positive nuclear ERCC1 expression was identified in 58.3% of the patients, ERCC1 expression was significantly associated with left-sided tumors (P< 0.01). Moreover, its expression was significantly associated with the aggressive tumor characteristics including high grade, lymph node metastasis and advanced tumor stage (P< 0.001 for each). High nuclear PARP-1 expression was observed in 63.3% of the cases, and its expression was significantly associated with tumor grade and lymph node metastasis (P= 0.003 for each). Positive membranous AQP1 expression was identified in 41.7% of patients, and it was associated with high grade, lymph node metastasis and advanced tumor stage (P< 0.001 for each). During the follow-up period, 23 patients (38.3%) exhibited a tumor progression; this was significantly associated with positive ERCC1, high PARP-1, and negative AQP1 expression. Statistics of the survival data revealed that shorter DFS was significantly associated with positive ERCC1, high PARP-1, and positive AQP1 expression (P= 0.005, 0.016, 0.002, respectively). CONCLUSIONS: ERCC1, PARP1, and AQP1 are adverse prognostic biomarkers in stage II-III colon cancer. Moreover, adjuvant chemotherapy may not be beneficial for patients with positive ERCC1, high PARP1, and AQP1-negative tumors. Therefore, we recommend that ERCC1, PARP-1, and AQP1 should be assessed during the selection of the treatment strategy for stage II-III colon cancer patients.

Prognostic implications of epithelial to mesenchymal transition related proteins (E-cadherin, Snail) and hypoxia inducible factor 1α in endometrioid endometrial carcinoma.

The epithelial-mesenchymal transition (EMT) is an important step in the invasion and metastasis of cancer. E-cadherin downregulation, which is essentially controlled by EMT-mediated proteins such as Snail, is a main molecular feature of this process. Tumor hypoxia is one of the essential biological phenomena that are associated with the development and progression of various solid tumors. Recently, hypoxia and hypoxia-inducible factor 1α (HIF-1α) signaling pathway were identified to have an essential role in the regulation of EMT phenotype. The aim of the study was to evaluate the prognostic impact of EMT-related proteins (E-cadherin, Snail) and HIF-1α in endometrioid endometrial carcinoma (EEC) among Egyptian women. Immunohistochemical evaluation of E-cadherin, Snail, and HIF-1α expression was performed using 50 cases of EEC. The relationship between protein expression and clinicopathological features was investigated. The frequency of immunopositivity for E-cadherin, Snail, and HIF-1α in our cases of EEC was 82%, 28%, and 66%, respectively. Reduced E-cadherin and increased nuclear expression of Snail as well as HIF-1α were significantly associated with histopathologic grade, clinical stage myometrial invasion, and lymph node involvement. Statistical analysis showed a positive correlation between HIF-1α overexpression and Snail upregulation (τ= +0.252, P= .025); however, E-cadherin expression level was inversely correlated with enhanced Snail expression (τ= -0.450, P< .001) as well as with HIF-1α overexpression (τ= -0.439, P< .001). The overall survival and progression-free survival were inversely related to Snail immunoreactivity and positively related to E-cadherin expression. E-cadherin and Snail have a predictive value in EEC. In conclusion, the current study reveals that both Snail and HIF-1α expressions are significantly associated with poor prognosis in EEC; however, E-cadherin expression is considered a marker of good prognosis. E-cadherin and Snail expression has a predictive value in EEC management.

Diagnostic value of IMP3 and mesothelin in differentiating pancreatic ductal adenocarcinoma from chronic pancreatitis.

BACKGROUND: The discrimination between pancreatic ductal adenocarcinoma (PDA) and chronic pancreatitis may be confusing at both clinical and radiologic levels. So, the search for biomarkers able to distinguish both clinical conditions is of great interest. AIM: This study was undertaken to assess the value of insulin-like growth factor II mRNA binding protein 3 (IMP3) and mesothelin to differentiate PDA from non-neoplastic/reactive pancreatic duct epithelium. METHODS: Immunohistochemical staining for IMP3 and mesothelin was performed on 40 formalin-fixed, paraffin-embedded tissue sections of PDA, 20 biopsies of chronic pancreatitis and 10 normal pancreatic tissue obtained from tumor-free surgical margins. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were calculated. RESULTS: IMP3 immunoreactivity was observed in 34 of 40 (85%) cases of PDA. The staining reaction was moderate to strong in 30 (75%) cases and diffuse in 26 (65%) cases. Eighteen of 20 (90%) biopsies of chronic pancreatitis were negative for IMP3, while the other two cases (10%) showed weak and focal IMP3 immunoreactivity. On the other hand, mesothelin demonstrated positive immunoreactivity in 30 of 40 (75%) cases of PDA. The staining reaction was moderate to strong in 24 (60%) cases and diffuse in 22 (55%) cases. Sixteen of 20 (80%) biopsies of chronic pancreatitis were negative for mesothelin, while weak and focal mesothelin staining was detected in the other 4 cases. All normal pancreatic tissues were negative for IMP3 and mesothelin expression. IMP3 showed higher sensitivity (85%) and specificity (90%) than mesothelin (75% and 80%, respectively). CONCLUSIONS: Our results showed that IMP3 immunostaining has a higher sensitivity and specificity than mesothelin for the diagnosis of PDA. IMP3 and mesothelin may be useful markers in distinguishing neoplastic from reactive lesions of the pancreas in instances where this is impossible by morphology alone in surgical pathology practice.