Related Study Between The Expression Of CD105 And VEGF In Pituitary Adenomas

ObjectiveThe aim is to compare the differences of the expression of CD105 and CD34 in pituitary adenomas, and to study the relationship between CD105-MVD and the expression of VEGF in invasive and non-invasive pituitary adenomas.Method1. Patient SelectionTissue samples were obtained from patients who underwent surgery in Shandong Provincial Hospital between December, 2003 and April, 2006. The total number of tissue samples is 48, including 29 males and 19 females with an average age of 39.3±1.4. All diagnoses of these cases were verified by immunohistochemical pathology. According to the display of images, cases were divided into 21 invasive cases and 27 non-invasive cases; 3 microadenomas (≤1cm), 10 small adenomas(1～2cm), 22 big adenomas (2～4cm)and 13 macroadenomas(≥4cm).2. ImmunohistochemistryPositive signals of CD105, CD34 and VEGF were detected by the S-P method with Ultrasensitive S-P kit.3. Result determinationMicro-vessels density (MVD) was calculated in CD105 and CD34. The counting employs Weidner method: First, select a microscopical field at magnification of 100×, search the hot-spots of micro-vessels, and then calculated them at a magnification of 400×by 5 selected fields. The counting is monitored by two pathologic physicians and the average numerical value is calculated at last. ≤1 MVD: (- ), 1 < MVD < 5: ( + ), 5≤MVD<10: ( + + ), 10≤MVD: ( + + + ) .In regular, the following 2 methods were employed to evaluate the expression of VEGF. First, Mattern method: First, the extent of positive staining (No staining: 0, slight staining: 1, medium staining: 2, deep staining: 3). Second, the percentage of positive cells (No staining is 0, <25% is 1 score, 25%～50% is 2 scores, >50% is 3 scores). Then adding the scores of two different methods, the highest score is 6. With the average score, 0～2 is negative, 3～4 is weak positive, 5～6 is strong positive.ResultsThe expression of CD34 in micro-vessels and large vessels was comparatively strong, and had a clear boundary with other tissues. Micro-vessels were stained into brown by the mark of CD105, but with a brown color not as obvious as CD34. In large vessels, the expression of CD105 was weak, but strong at the edge of the adenoma. The MVD of 48 cases with invasive pituitary adenoma and noninvasive pituitary adenoma, which were marked by CD105 antibody, were 21.12±0.75 and 10±0.48 and MVD, which were marked by CD34 antibody, were 34.85±0.84 and 25.04±0.43 respectively. The positive rate of VEGF was 72% and 36.4% respectively. There was a statistic significance in MVD marked by anti-CD 105 antibody in invasive pituitary adenoma(P<0. 01), but there was no statistic significance in MVD marked by anti-CD34 antibody between invasive pituitary adenomas and noninvasive pituitary adenomas. There was a significant positive correlation between MVD. which were marked by CD105 mab and CD34 mab, and expression of VEGF(P<0. 01).DiscussionThere was a positive expression in pituitary adenomas. Different invasive tumors had different stains. The color was strong in invasive pituitary adenomas, while weak in noninvasive pituitary adenomas. Much larger cavities and irregular shapes of hole were easily observed in invasive pituitary adenomas, and comparatively smaller cavities with fusiform shapes were common in noninvasive ones. Angiogenesis was the basic of tumor progress and metastasis. CD105 was involved in angiogenesis, and had a high expression on the endothelial cells. From this, we can presume that CD105 will play an important role in diagnosis, therapy and prognosis of malignant tumor.In our research, vessels in pituitary adenomas and in normal tissues were marked by anti-CD105 and anti-CD34 antibodies respectively. In invasive pituitary adenomas, though MVD marked by anti-CD105 antibody was lower than anti-CD34 antibody, there was statistic significance under the comparison in noninvasive pituitary adenomas(P<0. 01). However, there was no statistic significance in MVD marked by anti-CD34 antibody between invasive and noninvasive pituitary adenomas. In noninvasive pituitary adenomas, the expression of CD105 was weak, while CD34 was strong. In this way, if CD34 was used to mark endothelial cells, it would add to the rate of false positive rate. Therefore, the result illustrated that the expression of CD105 in pituitary adenomas was more specific than CD34.VEGF is one of the most important factors in promoting angiogenesis. VEGF can be specifically combined with the receptor of VEGF on vascular endothelial cells, and then stimulate the increase of endothelial cells and angiogenesis. In our research of 48 cases, 15 cases (72%) owned positive expression, which verified that pituitary adenomas had the ability of excreting VEGF. VEGF had a correlation with MVD marked by CD105 and CD34, but had a much closer relationship with CD105-MVD. So VEGF and MVD were good index to indicate the characteristics of tumors. Through the detection with the method of immunohistochemistry, these two index will help us to understand the initiate mechanism of invasive pituitary adenomas and biological behavior. We can make a prospective evaluation to invasive pituitary adenomas, and supply an important index for the diagnosis, differential diagnosis, therapy and prognosis of tumors.ConclusionThere was obvious expression of CD105 in pituitary adenomas, especially correlating with the invasion of adenomas. The detection of MVD marked by CD 105 is obviously more specific than that marked by CD34 in invasive pituitary adenomas. Thus, it is valuable to use CD105 in evaluating the situation of new vessel in pituitary adenomas. There was a close correlation between VEGF and MVD which were marked by CD105 and CD34, and both can be indications of invasive pituitary adenomas.