| Pituitary adenoma is one of the most common intracranial tumors in humans, accounts for about 15%～15% of intracranial tumors. Although pituitary adenoma belongs to benign tumor on histology, some of pituitary adenomas show invasive growth, invade cavernous sinus with encasing internal carotid artery and surrounding structure such as dura, bone, suprasellar and parasella, brain, etc. Some of pituitary adenomas are atypical adenomas with active growth, pathologically characterized by elevated mitosis, Ki-67 labeling index greater than 3% and positive p53 immunoreactivity. These tumors are difficult to resect totally, easy recurrence after surgery, drugs and radiation therapy is not satisfactory.Clinically, we call them invasive pituitary adenomas. Now its diagnostic criteria, operation method and molecular mechanism are all uncertain and controversial.In this paper, the following three aspects including diagnosis, surgical treatment and molecular mechanism of invasive pituitary adenomas were studied:1. The role of MRI, intraoperative exploration and pathology in the diagnosis of invasive pituitary adenoma; 2. Treatment of pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniques; 3. A preliminary research of miRNA on driving pituitary carcinoma metastasis and non-functioning pituitary adenoma invasive growth.Part one The role of MRI, intraoperative exploration and pathology in the diagnosis of invasive pituitary adenomaObjective To study the role of MRI, intraoperative exploration and pathology in diagnosis of invasive pituitary adenoma(IPA).Methods An analysis of the clinical data of MRI,surgery and pathology was taken in 125 cases of pituitary adenoma with the growth towards cavernous sinus,and to determine their invasiveness and to group them respectively on the basis of MRI, intraoperative exploration and pathology. MRI group:Knosp-Steiner grading scales Ⅲor IV as a inclusion criteria for IPA; Operation group:a hole or worn discovered in medial wall of cavernous sinus by intraoperative observation as a criteria. Pathology group:Ki-67 labeling index>3% as a criteria. Relevant statistical analysis was performed on them.Results MRI group:104 cases were identified as IPA. Operation group:92 cases were determined. Pathology group:14 cases were defined as IPA. The three groups were significant different in determining IPA (P=0.000), and pathology group compared with operation and MRI one respectively were also significant different (P=0.0000, P=0.000, respectively),whereas the comparision between MRI group and operation one was no significant different. (P>0.05). MRI demonstrated good diagnostic value on IPA (sensitivity 100%, specificity 63.6%, positive predictive value 88.5%, negative predictive value 100%) and had obviously higher accuracy than pathology(sensitivity 20.7%, specificity 84.8%, positive predictive value 79.2%, negative predictive value 27.7%)Conclusion In the diagnosis of IPA, MRI and intraoperative exploration have higher accuracy than pathology.Part two Treatment of pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniquesObjective To study the surgerical efficacy of giant pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by many technology.Methods Retrospective analysis of 72 cases of neuroendoscopic and 55 cases of microscopic surgery of giant pituitary adenomas, and two groups were taken expanded endoscopic endonasal transsphenoidal approach, intraoperative application of navigation and Doppler and the statistical analysis of clinical data.Results Neuroendoscopy and microscope group have statistically significant difference in tumor all cutting rate, operation time, nasal patency and postoperative recurrence rate (P=0.004,P=0.0003, P=0.000,P=0.002), but in the cerebrospinal fluid leakage, postoperative diabetes insipidus and cranial nerve injury were no statistically significant difference (P> 0.05)Conclusions Expanded neuroendoscopic endonasal transsphenoidal approach assisted by many technology is the preferred surgical method for giant invasive pituitary adenomas invading cavernous sinus. Lateral cavernous sinus approach and molecular biology research for the treatment of invasive pituitary adenomas provides more broad prospects.Part three A preliminary research of miRNA on driving pituitary carcinoma metastasis and non-functioning pituitary adenoma invasive growth.Objective Pituitary carcinomas are extremely rare neoplasms, and molecular events leading to malignant pituitary transformation and metastasis are largely unknown. Enhanced understanding of molecular mechanisms driving malignant pituitary progression will provide clues for the research of invasive growth of pituitary adenoma and be beneficial for pituitary carcinoma diagnosis and treatment.Methods Differential microRNA expression in paired primary and metastatic pituitary carcinoma specimens were detected using high-throughput human microRNA microarrays and TaqMan microRNA arrays. Three of significantly deregulated miRNAs were further confirmed using quantitative real-time PCR in the metastatic carcinoma,6 atypical pituitary adenomas and 8 typical pituitary adenomas. Target genes of microRNAs were bioinformatically predicated and verified in vitro by Western blotting and real-time PCR and in vivo by immunohistochemistry respectively.Results We present a case of a 50-year-old woman harboring non-functioning pituitary carcinoma with multiple intracranial metastases, and identified up-regulation of miR-20a, miR-106b and miR-17-5p in the metastatic carcinoma as compared to the primary neoplasm. Furthermore, miR-20a and miR-17-5p were increased in the metastatic carcinoma and 6 atypical pituitary adenomas as compared to 8 typical pituitary adenomas as measured by quantitative real-time PCR. Both PTEN and TIMP2 were bioinformatically predicated and confirmed in vitro as target genes of these three microRNAs. As semi-quantified by immunohistochemistry, PTEN was absent and TIMP2 was decreased in the metastatic pituitary carcinoma as compared to pituitary adenomas.Conclusions Our results suggest microRNA involvement in malignant pituitary progression and invasive growth, whereby increased miR-20a, miR-106b and miR-17-5p promote metastasis by attenuating PTEN and TIMP2 in pituitary carcinoma, and increased miR-20a and miR-17-5p drive invasive growth by attenuating PTEN and TIMP2 in non-functioning pituitary adenoma. |
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