Expression Of COX-2 And MMP-9 In Lacrimal Gland Epithelical Tumors And Relationship Of Clinical Prognosis

Background and purpose Tumor of lacrimal gland is one of the common orbit disease in clinic.They represent 7%-13% of all orbital apace-occupying lesions.The epithelial tumors accounted for about 70% of the lacrimal gland tumor.patients present with exophthalmos,displacement of the eyeball,swelling of the upper eyelid,blurred vision and diplopia.The persistent pain is characteristic of malignant tumors.These syndrome can significantly affect their appearance and daily life.Benign tumors can recurrence and malignancy;the malignant tumors are with high rates of Invasion and metastasis in the early days,10-year survival rate of ACC is less than 20%.In recent years,it is a hot research topic to search for new molecular markers for tumor of lacrimal gland patients to analysis prognostic and provide better personalized treatment.Cyclooxygenase(COX)is the rate limiting enzyme in the conversion of arachidonic acid to prostanoids.To date,two forms of COX,COX-1 and COX-2,have been identified.COX-1 is found at high levels of abundance in most tissues and cells in culture.The levels of COX-1 expression are relatively invariant.In recent years,Overexpression of COX-2 protein in several human carcinomas have been fund,which include Stomach,colon,lung,breast cancer and salivary gland tumors.COX-2 have been known that overexpression in various tumors is correlated with proliferation,progression,invasion and metastasis and angiogenesis to influence the prognosis of these tumors.Matrix metalloproteinases 9(MMP-9)is one of the members of the family of MMPs.It is a kind of calcium-zinc dependent proteins.Degrading basilar membrane of type IV collagen is the main function.Invasion and metastasis of tumors is a complex multi-step process.Degrading extracellular matrix is the crucial links.MMPs is the important protease which can take part in degrading EMC.MMP-9 can degrading basilar membrane of type IV collagen so it have been known that overexpression in various tumors is correlated with invasion and metastasis of tumors.In addition,in these process,MMP-9 maybe promote angiogenesis.In the study of colon cancer,pancreatic cancer,COX-2 and MMP-9 in these study found that there is a interaction between pathways.They can take part in the proliferation,progression,invasion and metastasis to become the influence factors of tumor prognosis.But the literature with two expression in tumors of lacrimal gland and its relationship are rarely reported.The samples were selected from lacrimal glands of 29 cases of ACC,37 cases of PA and 8 cases adjacent normal tissues.Expression of COX-2 and MMP-9 were detected by immunohistochemistry and then the clinical significance was analyzed.Materials and methods Research objects The samples were collected from the First Affiliated Hospital of Zhengzhou University from January 2004 to March 2015,66 cases of tumor of lacrimal gland were operated by ophthalmology and made a definite diagnosis by pathology department.These were 37 cases PA and 29 cases ACC.8 samples from lacrimal gland tissue around tumors were selected as the cotrol group.The PA group:there were 14 males and 23 females aged from 20 to 82 years old.The ACC group: there were 14 males and 15 females aged from 9 to 77 years old;Based on histological revision,there were 15 cases of cribriform-tubular subtype and 14 cases of solid subtype.All cases did not receive radiotherapy and chemotherapy before surgery.Methods The samples were selected from lacrimal glands of 29 cases of ACC,37 cases of PA and 8 cases adjacent normal tissues.Expression of COX-2 and MMP-9 were detected by immunohistochemistry.All patients are through phone call following-upor out-patient review to celect information.Statistical analysis using statistical software SPSS 17.0,using Mann-Whitney U rank sum test analysis COX-2 and MMP-9 in tumors of lacrimal gland of expression with Spearman method to analyze the correlation between the expression of COX-2 and MMP-9.Correction for continuity ?2 test was used to analysis the correlation between COX-2,MMP-9 and recurrence.P < 0.05 for differences were statistically significant.Results 1.COX-2 positive particle was localized in the cytoplasm of tumor cell.There was no positive expression in lacrimal gland around tumors.The positive rates of COX-2 in ACC and PA were 72.4% and 32.4% respectively.The positive rates of ACC was clearly higher than PA group(Z=-3.671;P<0.05).2.MMP-9 positive particle was localized in the cytoplasm or nucleus of tumor cell.There was no positive expression in lacrimal gland around tumors.The positive rates of MMP-9 in ACC and PA were 65.5% and 21.6% respectively.The positive rates of ACC was clearly higher than PA group(Z=-4.136;P<0.05).3.The expression of COX-2 was positively correlated with the expression of MMP-9 in 66 cases tumors of lacrimal gland.(r=0.673;P<0.01)4.Follow-up information found that 22 cases are recurrence in all 66 case patients.Though the correction for continuity ?2 test,the positive expression of COX-2 and MMP-9 patients had higher risk of recurrence than the negative(P<0.05).Conclusion(1)COX-2 and MMP-9 were highly expressed in lacrimal gland epithelial tumors,and there was no positive expression in lacrimal gland around tumors.The positive rates of ACC was clearly higher than PA group.(2)The expression of COX-2 was positively correlated with the expression of MMP-9 inlacrimal gland epithelial tumors.It suggested that there may be interaction between COX-2 and MMP-9.(3)The positive expression of COX-2 and MMP-9 patients had higher risk ofrecurrence than the negative.It suggested that COX-2 and MMP-9 may be closely related to the prognosis of patients.