Background Malignant pleural mesothelioma (MPM) is is one of most aggressive tumors with dismal prognosis. This poor prognosis necessitates deep understanding of different signaling pathway in order to improve prognostic prediction and therapeutic options. Macrophage migration inhibitory factor (MIF) and its receptor CD74 are found to be associated with poor prognosis in mesothelioma. However, this is still not well studied. Besides, the underlying mechanism of its action is in need for more understanding. Playing on immune checkpoints as well as angiogenesis are two of its potential mechanisms of action. Serum VEGF levels is one of the highest circulating markers in mesothelioma with correlation with poor prognosis. This study aimed at evaluating the expression of VEGF and CD74 on stored retrospective 50 paraffin embedded mesothelioma specimens. In 44 out of 50 of the cases, the relationship between both markers’ expression as well as tumor response to chemotherapy Gemcitabine and platinum combination was also studied. The study also elucidated the effect of VEGF and CD74 on the progression free survival (PFS) and overall survival (OS) of the studied patients. Patients and Methods Tissues were immunohistochemically stained for VEGF and CD74. The former was scored from 0 to 3 represent the percentage of cytoplasmic positively of stained tumour cells. The latter was scored in the tumor and the stroma in a sem-iquantitative manner using the histoscore method. Then after, Both CD74 and VEGF markers were furtherly categorized into none (0)/low (1) vs medium (2)/high expression (3) for statistical purposes. Results Poor response to gemcitabine and cisplatin chemotherapy was correlated with combined med/high expression of CD74-TS (P=0.03). High CD74 (T) and (S) as well as high VEGF expression were significantly correlated with short overall survival. Significant correlation is found between VEGF and each of CD74 (T) and CD74 (S) immunohistochemical expression levels. Conclusion High expression of CD74 T&S are inversely correlated with OS and response to Chemotherapy with Gemcytabine and cisplatin in mesothelioma patients.

Background: Malignant pleural mesothelioma is a fatal and aggressive disease; most patients present with advanced stages. Mesothelioma have one of the highest circulating serum VEGF levels of any solid tumor which is considered as a poor prognostic factor in this disease. Macrophage migration inhibitory factor (MIF) and its receptor CD74 found to be associated with angiogenic activity. Role of MIF has not been shown yet in MPM. This study targets the correlation between expression of VEGF and CD74 (on stored retrospective 44 paraffin embedded mesothelioma specimens) and tumor response to chemotherapy Gemcitabine and platinum combination. The study also figures out the prognostic impact of VEGF and CD74 on the progression free survival (PFS) and overall survival (OS) of the studied patients. Methods: Immunohistochemical staining for VEGF scored from 0 to 3 represent the percentage of cytoplasmic positively stained cells in the tumor. The CD74 expression was recorded in the tumor and the stroma semiquantitatively using the histoscore method with the final score resulting from the percentage of tumor cells staining positively multiplied by the staining intensity grade. Both CD74 and VEGF immunohistochemical markers were furtherly categorized in the statistical analyses as none (0)/low (1) vs medium (2)/high expression (3). Results: Combined med/high expression of CD74-TS and VEGF are significantly associated with poor response to gemcitabine and cisplatin chemotherapy (P = 0.03). VEGF expression level did not correlate with PFS (P = 0.09) while high CD74 (T) (P = 0.001) and (S) (P = 0.006) expression significantly impair PFS. Med/high VEGF expression is significantly associated with shorter OS (P = 0.025) whereas, med/high expression of CD74-TS yield a highly significant shorter OS. (P = 0.001). Conclusions: High expression of VEGF and CD74 T&S are inversely correlated with OS and response to chemotherapy with gemcitabine and cisplatin in Egyptian mesothelioma patients. Legal entity responsible for the study: Clinical Oncology Department Ethical Committe Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest.