Expression And Clinicopathological Significance Of BAP1,NF2,p16 And CUL1 In Malignant Mesothelioma

Background: Malignant mesothelioma(MM)is a kind of highly invasive malignant tumor.It is rare,and there is no special treatment,and the prognosis is poor.Because of its atypical clinical symptoms and various morphological and structural features,some special cases of MM may very similar to reactive mesothelial hyperplasia(BMP),benign adenomatoid tumor(AT)or metastatic adenocarcinoma(MAC),which cannot be distinguished only by morphology,especially in the limited biopsy materials.According to the research reports of MM genome structure in recent years,it was found that BaP1,NF2,CDKN2A/B,and CUL1 are the most frequent mutated genes in MM,and the corresponding key proteins are BaP1,NF2,p16,and CUL1.Objective: To study the protein expression of BaP1,NF2,p16 and CUL1 in MM,and to compare the expression of BaP1,NF2,p16,and CUL1 in MM,BMP and MAC.To explore the possible specific biomarkers of MM diagnosis and differential diagnosis,and their clinicopathological significance.Methods: Paraffin samples of 29 cases of MM,24 cases of AT,16 cases of BMP and 24 cases of MAC were collected from the First Affiliated Hospital of China Medical University from 2012 to 2018.The expression of BaP1,NF2,p16,and CUL1 in each case group was detected by immunohistochemistry.Results: The positive expression rates of BAP1 in MM,AT,BMP and MAC were 6.9%,0.0%,0.0%,and 12.5%.The positive expression rates of NF2 in MM,AT,BMP and MAC were 75.86%,79.17%,68.75%,and 83.33%.The positive expression rates of p16 in MM,AT,BMP and MAC were 44.83%,16.67%,25.0%,and 50.0%.The positive expression rates of CUL1 in MM,AT,BMP and MAC were 58.62%,29.17%,25.0%,and 79.17%.The expression difference of BAP1 and NF2 in MM,AT,BMP and MAC was not statistically significant(P > 0.05).The expression difference of p16 between MM and AT was statistically significant(?2 = 4.780,P = 0.029).The expression difference of p16 between MM,BMP and MAC was not significant statistically significant(P>0.05).p16 had no nuclear expression in AT and BMP,but in some cases of MM(13.79%,4/29)and MAC(20.83%,5/24),p16 was cytoplasmic and nuclear expression simultaneously.The expression difference between MM and MAC was not statistically significant(?2 = 0.462,P = 0.497).The expression difference of CUL1 between MM and AT(?2 = 4.598,P = 0.032)and BMP(?2 = 4.638,P = 0.030)is statistically significant(P < 0.05).The expression difference between MM and MAC was not statistically significant(P > 0.05).When Combined analyzed the expressions of NF2,p16 and CUL1 together,the expression difference between MM and AT was statistically significant(?2 = 4.369,P = 0.037),and the expression difference between MM,BMP,and MAC had not statistically significant(P> 0.05).The expressions of BAP1,NF2,p16,and CUL1 in malignant mesothelioma in pleura and peritoneum,respectively,was not statistically significant(P > 0.05).Conclusion: CUL1 expression was significantly different between MM,AT and BMP.Detection of CUL1 could help to distinguish MM from AT and BMP.Detection of p16 could help to distinguish MM from AT.Combined detection of NF2,p16,and CUL1 could help to distinguish MM from AT.Detecting the expression of BAP1 and NF2 alone had no significance in distinguishing MM,AT,BMP,and MAC.