Corresponding Research Of Cavernous Sinus Invasion Of Pituitary Adenomas

PART 1:THE ANATOMY RESEARCH OF INTERNAL WALL OF CAVERNOUS SINUS AND ITS MEANINGS TO THE DIAGNOSIS OF INVASIVENESSOF PITUITARY ADENOMASObjective: to investigate the anatomical characteristics of internal wall of cavernous sinus, and to know why pituitary adenomas incline to invade into cavernous sinus, so acquire the relationship between invasiveness of pituitary adenomas and cavernous sinus invasion.Methods:10 head specimens of adults and 1 child head specimen fixed by formaldehyde solution. we cut these specimens into 1cm thick slides and select the sellar region slides to observe the internal wall of cavernous sinus. 3 of them are coronal sections and 4 are axial sections , 3 are sagittal and 1 of them are skull base specimen. we observe the internal wall of cavernous sinus and take their pictures .we select some specimen to get the sellar part to embedded them with paraffin, and then make 4μm thick slides and dye them with hematoxylin-eosin and trichrome stains. We observe the internal wall of these slides at X 100 magnification to understand the microanatomical characteristics of pituitary capsule and internal wall of cavernous sinus.Results:1. there is no evident membrane can be seen between pituitary capsule and cavernous sinus, there is only some loose connective tissue and adipose tissue; 2. pituitary capsule is a thin transparent membrane, it interfere between the cavernous sinus and pituitary gland and at different site there is different thickness, varies from 30μm to 87μm but it is integrated; 3.there are three relationships between pituitary gland and cavernous segment of ICA: 6 of 32 sides the pituitary gland contact directly with the ICA; 18 of 32 there have different size space; and the other the pituitary gland protrude into upper part of ICA like a tongue.Conclusions: 1. there is no evident membrane between pituitary capsule and cavernous sinus, there is only some loose connective tissue and adipose tissue; 2. pituitary gland can contact directly with ICA , sometimes protrude into upper part of ICA like a tongue, or there are different thin compartment; 3. the anatomic structures beyond pituitary capsule varies largely, there is visceral dura at anterior, posterior and inferior site beyond pituitary capsule, so at these sites the thickness beyond pituitary capsule is much thicker than that of parasellar part of pituitary capsule,so there is congenital weakness at internal space of CS.PART 2:THE EXPRESSION OF KI-67 AND PTTG IN PITUITARY ADENOMAS INVADING INTO CAVERNOUS SINUS ANDITS MEANINGS TO PREDICT INVASIVENESSObjective: to investigate the expression of Ki-67 and PTTG in pituitary adenomas invading into cavernous sinus, to learn about the mechanism of tumor CS invasiveness from biomolecular basis. Methods: Collect 60 examples during surgery in Shandong Provintial hospital from 2005 to 2007, among them 29 patients are male and 31 female, age from 15 to 56 years old, mean age is 29. 5. according to clinical symptom and serum hormones there are 21 PRL adenomas and 18 GH adenomas, 17 nonfunctional adenomas and 4 multi-functional adenomas. According to tumor size there are 42 large adenomas and 18 giant adenomas. according to tumor invasiveness: there are 36 CS invasive pituitary adenomas and 24 noninvasive adenomas. We give MRI examination to all patients. According to Knosp standard we define grade III and IV as invasive adenomas , adenomas with dura invasion and grows into cavernous sinus are also defined as invasive adenomas. we embed all specimens with paraffin, cut them into 4um thick slides and dye them with Ki-67 and PTTG antibody using ABC immunohistochemical dying method, then we count positive-dying cells under microscope. Analyze the values between different groups with SPSS11.0 package. Compare Ki-67 or PTTG values between different groups using Chi-square test methods, p value is less than 0.05.Results: 1. PTTG positive - dying adenomas is83. 3%(30/36) in CS invasive group, and 58. 3%(14/24) in CS noninvasive group( x~2=4. 60, p=0.033), there is significant statistical differentiation. PTTG+ have 83.3 % sensitivity to diagnose invasion and 41.7% positive predict value; the sensitivity of PTTG++ is 66.7% and positive predict value is 66.7%; PTTG+++ sensitivity is 36.2% and positive predict value is 87.5%. there are 6 adenomas is negative-dying of PTTG; 2. Ki-67 strong positive-dying are 47.2%(17/36)in CS invasive group and 33. 3%(8/24)in noninvasive group, ( x~2 = 6.407,p= 0.011 ) .there is significant statistical differentiation. But 30. 6%(11/36)adenomas the value is less than l%;also in CS noninvasive group there is 45. 8%(11/24)the value is less than 1%, ( x~2 = 1.447,p = 0.23 ), there is no significant statistical differentiation. 3. Ki-67 strong positive-dying is 50%(22/44)in PTTG positive-dying group, andl8. 75%(3/16) in PTTG negative-dying group, there is significant statistical differentiation between them.Conclusions: 1.the positive-dying incidence of PTTG and Ki-67 in CS invasive pituitary adenomas is higher than noninvasive group, PTTG ++ have more meanings to predict the invasiveness of adenomas. PTTG and Ki-67 have important synergistic effect to induce the CS invasiveness of pituitary adenomas;high cell proliferation rate can predict invasive behavior of pituitary adenomas, but low cell proliferation rate cannot exclude invasive behavior. 2. PTTG and Ki-67 expression present positive correlation in invasive adenomas, so PTTG probably leads to invasiveness by promoting cell proliferation. But this is not the singular mechanism.PART 3:THE PROLIFERATION AND APOPTOSIS RESEARCH OF PITUITARY ADENOMAS INVADING INTO CAVERNOUSSINUS AND ITS MEANING TO PREDICT INVASIVENESSObjective: Now there are many parameters to predict the invasiveness of pituitary adenomas, but none of them are satisfying, so we research the proliferation and apoptosis parameter at the same time in order to acquire a good predicting standard.Methods: To research the fresh specimen of pituitary adenomas of our hospital from 12, 2005 to 12, 2006. according to the surgical evidence of invasiveness we divided them into cavernous sinus invasive group and noninvasive group. We performed the analysis of DNA ploid and test apoptosis value using Annexin- V and PI double-dying method with flow-cytometric quantitation. The percentage of cells in S-Phase(%SPH) were obtained in 33 pituitary adenomas and at the same time we obtained the apoptosis value of them , then we calculate the ratio of the apoptosis value and %SPH . using SPSS11.0 we compare the results.Results: 1. results of DNA ploidy: the SPH% of CS invasive group is 3.9～24.2%, mean value is 13. 04 + 3. 60%, SPH% of CS invasive group is 0.8～12.2 %, mean value is 4.78±1.99%. the value of CS invasive group is higher than CS noninvasive group, there is significant differences (t = 3.745, p= 0.001). if we define 13. 04% as the dividing point, it has a 100% positive predictive value to predict CS invasiveness, but its sensitivity is only 40 percents; 2. results of cell apoptosis:the percentage of cell apoptosis of CS invasive group is 5.14～27%, mean value is 12. 53 + 3. 75%, the percentage of CS noninvasive group is 3.6～30.3%, mean value is 16.15±3.63%, the percentage of cell apoptosis of CS invasive group is lower than CS noninvasive group, but also there is no significant differentiation(t = 1.25, p=0.22). if we define 12. 53% as a dividing point, the PPV of cell apoptosis less than 12. 53% to diagnose invasiveness is 66.7%, and sensivity is 80%; 3. results of ratio of proliferation and apoptosis: the value of CS invasive group is 0.144～2.305, mean value is 1. 411+0. 385, the value of CS noninvasive group is 0.134～1.315, mean value is 0.399 + 0. 191, the value of S/A of CS invasive group is higher than CS noninvasive group, and the difference has significant differentiation(t = 4.62, p< 0.0001).if we define 1.411 as a dividing point of invasiveness. The ppv of value higher than than is 100%, and sensitivity is 60%.Conclusion: high proliferation state can lead to CS invasiveness, but low proliferation state cannot exclude CS invasiveness. Apoptosis value of CS invasive group is less than CS noninvasive group, but it seems no meanings to lead to invasiveness of pituitary adenomas alone. cell proliferation and cell apoptosis both have some important meanings to lead to the CS invasiveness of pituitary adenomas, the disequilibrium of proliferation and apoptosis finally leads to its CS invasivenss. so S/A is an accurate and specific index to predict invasiveness, this value can predict invasiveness early and accurately. so based on our results we think we can predict invasiveness of pituitary adenomas which localized in sellar region that not contact pituitary capsule, and follow them up strictly.