Immunohistochemical expression of CD163 in colorectal carcinoma and its prognostic value

Background/aim Colorectal cancer (CRC) is one of the most frequent cancers worldwide with one of the highest mortality rate. CD163 is a 130-KDa transmembrane protein, known to be involved in hemoglobin clearance by functioning as a receptor for hemoglobin–haptoglobin complex. Several studies have demonstrated that CD163 is expressed on some cancer cells, and its expression is associated with poor clinical prognosis. This study aimed to evaluate CD163 to assess the distribution of macrophages in invasive margins and intratumoral infiltration area, using computerized image analysis, to evaluate its prognostic value and its association with other clinicopathological characteristics in colorectal carcinoma. Patients and methods The present study enrolled 80 formalin-fixed paraffin-embedded CRC surgical specimens, obtained from the Department of Pathology of National Research Centre, Egypt, and examined for the expression of CD163 in CRCs by immunohistochemical techniques. The morphometric analysis was done on the invasive margins and intratumoral infiltration area in each slide. Results The study cases of colorectal carcinoma patients, 46 (57.5%) cases were diagnosed as adenocarcinoma and rest 34 (42.5%) cases were mucinous carcinoma. Twenty-two cases (22/80) showed a low intratumoral infiltration area and moderate invasive margin. CD163+ intratumoral infiltration significantly correlated with age, tumor site, tumor type, lymph node status, and metastasis. On the other hand, CD163+ invasive margins significantly correlated with tumor grade, tumor classification, metastatic status, tumor stage, and Duke’s classification. Conclusion Invasive front of the tumor is the most suitable area for the evaluation of tumor-associated macrophages that is important in detecting prognostic prediction of colon cancer and its clinical outcome. So, it can be considered as an ideal prognostic marker in the treatment of colon cancer

Microsatellite instability screening in colorectal carcinoma: immunohistochemical analysis of MMR proteins in correlation with clinicopathological features and Ki-67 protein expression

Abstract Background Defects in mismatch repair (MMR) system or microsatellite instability (MSI) and detected in colorectal carcinoma (CRC), both in sporadic and more frequently in hereditary cases. Immunohistochemistry (IHC) is the most frequent method for MMR protein deficiency screening in CRCs. In this study, we aimed to evaluate immunohistochemical expression of MMR and Ki-67 in colorectal carcinoma with clinicopathological features. Methods In this study, we evaluated the immunohistochemical expression of MMR proteins including MSH6, MSH2, PMS2 and MLH1 in 50 resection materials with colorectal carcinoma. Their expression is correlated with clinicopathological features of patients together, with Ki-67 protein expression in attempt to screen the most significant predictor of microsatellite instability. Results Of the 50 cases of cancer colon, 28% were classified as MSI-H, 20% were MSI-L, and 52% were MSS. The most frequent pattern in MSI-H tumors was concurrent loss of MSH6 and PMS2 proteins. There was a significant correlation between MMR protein expression pattern with tumor size, grade, T-classification and stage (0.015, 0.0515, 0.0162 and 0.0391), respectively. MSI-H tumors were located more frequently in right colon, early TNM stage and poorly differentiated and infrequent distant metastases. There was a significant correlation between Ki-67 high expression and MSI status patterns in their common biological aspects distinct from MSI-negative tumors. Conclusions Mismatch repair defective colorectal carcinoma has characteristics clinicopathological features different from MSS tumors. The role of immunohistochemistry (IHC) for MSI evaluation is the easiest and effective way for evaluation of MMR deficiency in colorectal carcinoma

Immunogenicity and Safety of an Inactivated SARS-CoV-2 Vaccine: Preclinical Studies

Since the emergence of SARS-CoV-2 at the end of 2019, 64 candidate vaccines are in clinical development and 173 are in the pre-clinical phase. Five types of vaccines are currently approved for emergency use in many countries (Inactivated, Sinopharm; Viral-vector, Astrazeneca, and Gamaleya Research Institute; mRNA, Moderna, and BioNTech/Pfizer). The main challenge in this pandemic was the availability to produce an effective vaccine to be distributed to the world’s population in a short time. Herein, we developed a whole virus NRC-VACC-01 inactivated candidate SARS-CoV-2 vaccine and tested its safety and immunogenicity in laboratory animals. In the preclinical studies, we used four experimental animals (mice, rats, guinea pigs, and hamsters). Antibodies were detected as of week three post vaccination and continued up to week ten in the four experimental models. Safety evaluation of NRC-VACC-01 inactivated candidate vaccine in rats revealed that the vaccine was highly tolerable. By studying the effect of booster dose in the immunological profile of vaccinated mice, we observed an increase in neutralizing antibody titers after the booster shot, thus a booster dose was highly recommended after week three or four. Challenge infection of hamsters showed that the vaccinated group had lower morbidity and shedding than the control group. A phase I clinical trial will be performed to assess safety in human subjects

Immunogenicity and Safety of an Inactivated SARS-CoV-2 Vaccine: Preclinical Studies

Since the emergence of SARS-CoV-2 at the end of 2019, 64 candidate vaccines are in clinical development and 173 are in the pre-clinical phase. Five types of vaccines are currently approved for emergency use in many countries (Inactivated, Sinopharm; Viral-vector, Astrazeneca, and Gamaleya Research Institute; mRNA, Moderna, and BioNTech/Pfizer). The main challenge in this pandemic was the availability to produce an effective vaccine to be distributed to the world’s population in a short time. Herein, we developed a whole virus NRC-VACC-01 inactivated candidate SARS-CoV-2 vaccine and tested its safety and immunogenicity in laboratory animals. In the preclinical studies, we used four experimental animals (mice, rats, guinea pigs, and hamsters). Antibodies were detected as of week three post vaccination and continued up to week ten in the four experimental models. Safety evaluation of NRC-VACC-01 inactivated candidate vaccine in rats revealed that the vaccine was highly tolerable. By studying the effect of booster dose in the immunological profile of vaccinated mice, we observed an increase in neutralizing antibody titers after the booster shot, thus a booster dose was highly recommended after week three or four. Challenge infection of hamsters showed that the vaccinated group had lower morbidity and shedding than the control group. A phase I clinical trial will be performed to assess safety in human subjects