The Expression Of Cyclooxygenase-2 And CD34 In Premalignant Vulvar Disorders And Vulvar Squamocellular Carcinoma

Abstract:Objectives:Carcinogenisis and its development relate to many factors and the angiogenesis fators is one of the pivotal agents. The contemporary researches suggest that the cyclooxygenase-2 promotes the carcinoma neovasculature through multiple pathways. The nonneoplastic epithelial disorders of vulva (NNEDV) and the vulvar intraepithelial neoplasia(VIN) are regarded as the precursors of the vulvar carcinoma. NNEDV is uncurable and the risk of progression to vulvar carcinoma is up to 9%. There were several therapies used to treat the vulvar carcinoma, but the traditional therapies have not definitive effectiveness. The patients' compilantce were poor. The high focused ultrasound (HIFU) is a new physical therapy for NNEDV in recent years, which had been paid close attention for its non-invasiveness, safety and fast effectiveness. This study was designed to investigate the expression of the cyclooxygenase-2 and CD34 in nonneoplastic epithelial disorders of vulva, neoplastic epithelial disorders of vulva and vulvar carcinoma to explore the role of cyclooxygenase-2 and CD34 in vulvar carcinogenesis and its progression. Meanwhile, the study assessed the effectiveness and investigated the mechanism of the HIFU by comparision of expression changes of cyclooxygenase-2 and CD34 in pre-treatment and post-treatment samples. Methods:1.147 documented paraffin blocks of nonneoplasia epithelial disorder of vulvar, vulvar intraepithelial neoplasia and vulvar squamocellular carcinoma diagnosed in department of pathology of Affiliated Hospital of Luzhou Medical College from January 2003 to July 2006 were enrolled. That is to say,107 samples of NNEDV including 52 cases of squamocellular hyperplasia,37 cases of lichen scleroses,18 cases of other dermatoses.42 cases of vulvar intraepithelial neoplasia including 17cases of VIN I,14 cases of VINâ…¡,11 cases of VINâ…¢.34 cases of vulvar squamocellular carcinoma,10 cases of normal skin were collected from the out-patient clinic of Department of Gynecology and Obstetrics of Affiliated Hospital of Luzhou Medical College. The clinical pathological characteristics of VSCC patients including age, FIGO stage, and lymphatic node metastasis were analyzed. The samples were analyzed by paraffin imbed, hematoxylin-eosin dying and immunohistochemistry. All image data of the samples was inputted into the ImagePro software 4.0 version. The microvessel internal surface area was measured by cycloid grid intersection method and the microvessel internal surface area (Sv) was unbias-estimated by stereological method. The datum analysis was conducted by SPSS version 16.0.2. The 29 samples of NNEDV group, including 20 cases of squamocellular hyperplasia, 10 cases of lichen scleroses were collected in out-patient clinic of Department of Gynecology and Obstetrics of Affiliated Hospital of Luzhou Medical College from August 2006 to January 2008. All patients were treated by focused ultrasound. The 19 cases of SH and 10 cases of LS were followed up and assessed the effectiveness after six months. The 11 cases of SH and 7 cases of LS were repeated biopsy at the lesion in situ after focused ultrasound treatment from 5 to 12 months (the mean time 8 months). The samples were analyzed by paraffin imbed, hematoxylin-eosin dying and immunohistochemistry. All image data of the samples was inputted into the ImagePro software 4.0 version. The microvessel internal surface area was measured by cycloid grid intersection method and the microvessel internal surface area (Sv) was unbias-estimated by stereological method. The datum analysis was conducted by SPSS version 16.0. Results:1. The expression of COX-2 in different vulvar disorders:In NNEDV, the expression dendity of COX-2 in LS was significantly higher than in SH and in others dermatoses. There was no statistically significant difference among in SH and in others dermatoses. In VIN, the expression dendity of COX-2 in VINâ…¢were significantly higher than in VINâ…¡and in VINâ… . There was no statistically significant difference among in VINâ…¡and in VINâ… . The rate of positive area and optical density of COX-2 expresssion in vulvar squamocellular carcinoma (keratinizing-type) were significantly higher than in VIN and in NNEDV. The correlation between COX-2 and the pathological characteristics of vulvar carcinoma:according to FIGO staging, the expression of COX-2 in stageâ…¢vulvar squamocellular carcinoma were significantly higher than in stageâ… and in stageâ…¡(P<0.05). The expression of COX-2 in VSCC with lymphatic node metastasis was significantly higher than without lymphatic node metastasis. The expression of COX-2 related to the FIGO stage but was independent of patients'age.2. The expression of CD34 in different vulvar disorders:In NNEDV, the microvessel internal surface area in LS was significantly lower than in SH and in the others dermatoses. There was no significant difference between SH and the others dermatoses. The microvessel internal surface area in VIN was significantly higher than in NNEDV (P<0.05). The microvessel internal surface area in VINâ…¢was significantly higher than in VINâ…¡and in VINâ… . There was no statistically significant difference among in VINâ…¡and in VINâ… (P=0.289).The microvessel internal surface area in VSCC was significantly higher than in VIN and in NNEDV. The correlation between CD34 and the pathological characteristics of vulvar carcinoma:according to FIGO stage, the expression of CD34 in stageâ…¢vulvar squamocellular carcinoma was significantly higher than in stageâ… and in stageâ…¡. The expression of CD34 in VSCC with lymphatic node metastasis was significantly higher than without lymphatic node metastasis. The expression of CD34 related to the FIGO stage but was independent of patients'age. According to FIGO stage, the higher stage of VSCC had the higher microvessel internal surface area, that is to say, stageâ…¢> stageâ…¡> stageâ… 3. There was a positive correlation of the expression between COX-2 and CD34 in VIN. There was a positive correlation of the expression between COX-2 and CD34 in VSCC.4. After six monthes HIFU treatment,10 cases of 29 cases NNEDV was clinically cured (34.5%), effective (55.2%%), the total effectiveness rate was 89.7%.5. The rate of positive area and optical density of COX-2 expression in post-treatment NNEDV was significant lower than in pre-treatment (P<0.05), but was minorly higher than in normal group. The expression of CD34 in post-treatment NNEDV was significantly higher than in pre-treatment, but was minorly lower than in normal group.Conclusions:1. The vascular microstructure of nonneoplastic epithelial disorders of vulva was dysfunctional, in which the microvascular significantly decreased, especially in lichen sclerosus. It suggests the dysfunctional vascular is one of the characteristic changes.2. The cyclooxygenase-2 plays a significant role in the genisis and progression of the vulvar squmocellular carcinoma. The detection of cyclooxygenase-2 expression in nonneoplastic epithelial disorders and lichen sclerosus of vulva could be an indicator for lesion progression to carcinoma in followup, condidering that the NNEDV and VIN had the possibility of carcinomatous change.4. The expression of CD34 and COX2 related to the malignant progression of the vulvar squemocellular carcinoma. The higher expression of CD34 and COX2 was found in vulvar squemocellular carcinoma with higher FIGO stage and lymphatic node metastasis. There was a positive expression correlation between COX-2 and CD34 in the vulvar squemocellular carcinoma.5. The high focused ultrasound therapy had a definitive effectiveness, which not only cure or relieve the symptoms of refractory itching, recuperate microstructure of vulvar epithelial tissue, but also facilitate the formation of the microvasculature in dermis and reduce the expression of cyclooxygenase-2.