Lack of correlation between Ki-67 labelling index and tumor size of anterior pituitary adenomas

AIMS AND BACKGROUND: The Ki-67 is a nuclear antigen detected by the monoclonal antibody MIB-1 and its Labeling Index (LI) is considered a marker of normal and abnormal cell proliferation. Pituitary adenomas are generally well differentiated neoplasms, even if in about one third of cases they are invasive of surrounding tissues. The aim of this study is to evaluate the correlation between Ki-67 labelling index and tumor size of pituitary adenomas extimated by means CT and MRI and confirmed at operation. METHODS: Using the monoclonal antibody MIB-1, we evaluated the expression of Ki-67 in 121 anterior pituitary adenomas consecutively operated on in a 48-month period. RESULTS: In relation to neuroradiological (CT and MRI) and surgically verified tumor size, we identified 24 microadenomas, 27 intrasellar macroadenomas, 34 intra-suprasellar macroadenomas, and 36 intra-supra-parasellar macroadenomas. The adenomas were non-infiltrating (76 cases) and infiltrating (45 cases) adenomas. The wall of the cavernous sinus (CS) was infiltrated in 18 cases. Forty-eight adenomas were non-functioning and 73 functioning. The overall mean ± SD Ki-67 LI was 2.72 ± 2.49% (median 1.6). It was 2.59 ± 1.81 in microadenomas, 2.63 ± 3.45 in intrasellar macroadenomas, 1.91 ± 2.11 in intra-suprasellar macroadenomas, and 3.29 ± 5.45 in intra-supra-parasellar macroadenomas (p = 0.27). It was 3.73 ± 5.13% in infiltrating and 2.03 ± 2.41% in non-infiltrating adenomas (p = 0.02), and 5.61 ± 7.19% in CS-infiltrating versus 2.09 ± 2.37% in CS-non-infiltrating adenomas (p = 0.0005). CONCLUSIONS: Our preliminary results seem to exclude significative correlations between Ki-67 LI and tumor size of anterior pituitary adenomas, even if this index can be considered a useful marker in the determination of the infiltrative behaviour of these tumors

Clinical Significance of Ki-67 Labeling Index in Pituitary Macroadenoma

The aim of our study was to investigate the correlation of the proliferative activity of pituitary neoplasms with clinical characteristics and recurrences. Tumor specimens were obtained from 44 consecutive patients with pituitary macroadenomas who underwent surgery between July 1998 and August 2003. Specimens were immediately fixed in 10% buffered formalin and then embedded in paraffin. The Ki-67 antigen was assessed by immumohistochemical analysis using the monoclonal antibody. We investigated the correlation of the Ki-67 labeling index with the following clinical and radiological characteristics: sex, age, presence or absence visual field defect, tumor classification, maximal tumor diameter, Hardy's classification, type of tumor, invasiveness, and recurrence. Our study suggests that the clinical characteristics such as visual field defect and recurrence are correlated with the high Ki-67 labeling index. No statistical differences were observed in the Ki-67 labeling index in relation to the following characteristics: sex, age, tumor classification, maximal tumor diameter, Hardy's classification, type of tumor, and invasiveness into the sphenoid sinus or cavernous sinus

Advances in the treatment of prolactinomas

Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future