scholarly journals Effects of Octreotide Treatment on the Proliferation and Apoptotic Index of GH-Secreting Pituitary Adenomas

2001 ◽  
Vol 86 (11) ◽  
pp. 5194-5200 ◽  
Author(s):  
Marco Losa ◽  
Enrica Ciccarelli ◽  
Pietro Mortini ◽  
Raffaella Barzaghi ◽  
Daniela Gaia ◽  
...  

To investigate the effects of octreotide administration on the growth rate of GH-secreting pituitary adenomas, we measured both the Ki-67 labeling index (LI) and the apoptotic index in tumor specimens from octreotide-treated or matched untreated acromegalic patients. Thirty-nine patients who received octreotide until the day of or the day before surgery and 39 untreated patients matched for sex, age, tumor size, extension, and invasiveness were studied. Immunocytochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick endlabeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. The Ki-67 LI and apoptosis were counted on separate slides in at least 1000 evaluable cells. Octreotide-treated patients showed a lower Ki-67 LI (1.8 ± 0.3%) than untreated controls (3.8 ± 0.7%; P < 0.02). Overall, the mean Ki-67 LI of treated patients was 53% lower than that in untreated patients. The antiproliferative effect of octreotide occurred independently of tumor extension and invasiveness. Octreotide-treated and untreated patients showed similar apoptotic indexes (0.6 ± 0.2% and 0.8 ± 0.3%, respectively). There was a positive correlation between the Ki-67 LI and the apoptotic index (r = 0.29; P< 0.03). Our study demonstrates that acromegalic patients receiving chronic octreotide treatment have a lower value of the proliferation marker Ki-67, but no significant difference in the apoptotic index compared with matched untreated patients. The antiproliferative effect of octreotide on GH-secreting adenomas should imply a lower risk of tumor growth during long-term chronic treatment with the drug.

Neurosurgery ◽  
1989 ◽  
Vol 25 (6) ◽  
pp. 927-930 ◽  
Author(s):  
Engelbert Knosp ◽  
Klaus Kitz ◽  
Axel Perneczky

Abstract The monoclonal antibody (MAb) Ki-67 detects a nuclear antigen expressed by proliferating cells during the entire cell cycle. In contrast to conventional histological techniques, the use of MAb Ki-67 on frozen sections or cytological smear preparations allows direct determination of the growth rate of tumors routinely. Sixty-two pituitary adenomas were investigated by use of the MAb Ki-67 in a two-step avidin-biotin-peroxidase complex technique. The proliferation activity ranged from 0.1 to 2.8%. There was no significant difference between the proliferation and hormonal state of the adenomas. Adenomas for which there was histological evidence of dural infiltration, however, showed a statistically significant higher proliferation activity (P> 0.05) compared to noninvasive adenomas.


1987 ◽  
Vol 67 (6) ◽  
pp. 803-806 ◽  
Author(s):  
Alex M. Landolt ◽  
Taichiro Shibata ◽  
Paul Kleihues

✓ The immunohistological detection of a proliferation-associated nuclear antigen by the monoclonal antibody Ki-67 allows the determination of the growth fraction in human cell populations. In this study, biopsy specimens of 31 pituitary adenomas representing all major endocrine types were examined. All adenomas contained proliferating cells and the percentage of nuclei that were immunoreactive to Ki-67 ranged from 0.1% to 3.7%. Low values (0.1% to 1.0%) were present in 11 endocrine-inactive adenomas and higher values (1.1% to 1.5%) were found in six acromegalic patients. The percentages of Ki-67-positive cells in 12 prolactinomas and two adenomas from patients with Cushing's disease covered the entire range (0.1% to 3.7%). Preoperative bromocriptine treatment of prolactinomas did not influence Ki-67 expression. Invasive adenomas, as determined by preoperative computerized tomography, surgical observation, and histological examination of the sella dura demonstrated significantly higher Ki-67 values (average 1.15%) than noninvasive adenomas (average 0.60%). Determination of the incidence of proliferating cells by Ki-67 immunoreactivity represents a new tool for intraoperative quantitative assessment of tumor growth characteristics and may aid in the planning of adjuvant therapy and estimation of prognosis.


2009 ◽  
Vol 111 (3) ◽  
pp. 563-571 ◽  
Author(s):  
Georg Widhalm ◽  
Stefan Wolfsberger ◽  
Matthias Preusser ◽  
Ingeborg Fischer ◽  
Adelheid Woehrer ◽  
...  

Object In residual nonfunctioning pituitary adenomas, reliable prognostic parameters indicating probability of tumor progression are needed. The Ki 67 expression/MIB-1 labeling index (LI) is considered to be a promising candidate factor. The aim in the present study was to analyze the clinical usefulness of MIB-1 LI for prognosis of tumor progression. Methods The authors studied a cohort of 92 patients with nonfunctioning pituitary adenomas. Based on sequential postoperative MR images, patients were classified as tumor free (51 patients) or as harboring residual tumor (41 individuals). The residual tumor group was further subdivided in groups with stable residual tumors (14 patients) or progressive residual tumors (27 patients). The MIB-1 LI was assessed in tumor specimens obtained in all patients, and statistical comparisons of MIB-1 LI of the various subgroups were performed. Results . The authors found no significant difference of MIB-1 LI in the residual tumor group compared with the tumor-free group. However, MIB-1 LI was significantly higher in the progressive residual tumor group, compared with the stable residual tumor group. Additionally, the time period to second surgery was significantly shorter in residual adenomas showing an MIB-1 LI > 3%. Conclusions The data indicate that MIB-1 LI in nonfunctioning pituitary adenomas is a clinically useful prognostic parameter indicating probability of progression of postoperative tumor remnants. The MIB-1 LI may be helpful in decisions of postoperative disease management (for example, frequency of radiographic intervals, planning for reoperation, radiotherapy, and/or radiosurgery).


1995 ◽  
Vol 12 (3) ◽  
pp. 234-238 ◽  
Author(s):  
James Linder ◽  
Lambert Skoog ◽  
Edneia Tani ◽  
Erik Svedmyr ◽  
Bo Johansson

Skull Base ◽  
1991 ◽  
Vol 1 (01) ◽  
pp. 11-15 ◽  
Author(s):  
T. H. J. Lesser ◽  
R. C. Janzer ◽  
P. Kleihues ◽  
U. Fisch

2008 ◽  
Vol 31 (1) ◽  
pp. 8 ◽  
Author(s):  
WeiDe Zhong ◽  
Jinyu Peng ◽  
HuiChan He ◽  
Dinglan Wu ◽  
ZhaoDong Han ◽  
...  

Objective: Ki-67 is a proliferation-associated nuclear antigen and is expressed in all cycling cells except for resting cells in the G0-phase. PCNA is an acidic nuclear protein and has been recognized as a histologic marker for the G1/S phase in the cell cycle. Ki-67and PCNA labeling indices are considered to reflect cell proliferation, particularly, growth fraction. The purpose of this study is to investigate the expression levels of Ki-67 and PCNA in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their potential on the early diagnosis of PCa. Methods: Human prostate cancer cell lines LNCaP and PC-3, human normal prostate epithelial cell line HuPEC, tissues from patients with PCa (121 cases) and BPH (45) and 36 normal cases were examined for the expression of Ki-67 and PCNA by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Then, the association of Ki-67 and PCNA expression with clinical grading of PCa was analyzed by immunohistochemistry staining. Results: The ratios of PCNA and Ki-67 expression levels in LNCaP and PC-3 were higher (P < 0.05, P < 0.001) than that in HuPEC. The two markers were differentially expressed in three tissues and showed increased expression in PCa (P < 0.05) and BPH (P < 0.05), relative to human normal prostate tissues. Compared with BPH, the ratio of Ki-67 and PCNA expressed in tumour tissue was increased (P < 0.05). The increase of Ki-67 was greater than that of PCNA. Expression of the two markers increased after different grading of PCa cases. The values of Ki-67/PCNA were: 0.073 in grade I PCa tissues, 0.119 in grade IIa PCa tissues, 0.141 in grade IIa PCa tissues, 0.234 in grade III PCa tissues. Conclusion: The combination of Ki-67 and PCNA, specific proliferative markers of PCa, may improve the accuracy of early diagnosis of prostatic cancer.


Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 1157-1160 ◽  
Author(s):  
TM Grogan ◽  
SM Lippman ◽  
CM Spier ◽  
DJ Slymen ◽  
JA Rybski ◽  
...  

Abstract To assess the prognostic significance of the growth fraction in diffuse large cell lymphoma (DLCL), we studied 105 DLCL patients with the monoclonal antibody Ki-67 applied to frozen tissue sections. Ki-67 detects a nuclear antigen associated with cell proliferation not found in resting cells. Ki-67 findings and other clinical prognostic factors were correlated with outcome using univariate and multivariate analyses in the proportional hazards model. High proliferative activity, defined as nuclear Ki-67 expression in greater than 60% of malignant cells (Ki- 67 greater than 60), was found to be a strong predictor of poor survival among these patients (P = .003, log-rank). The 19 patients with Ki-67 greater than 60% had a median survival of 8 months compared with a median survival of 39 months for the 86 patients with Ki-67 less than or equal to 60%. Examination of pretreatment clinical variables indicated the patient groups were similar with regard to age, sex, stage, B symptoms, tumor bulk, and lactate dehydrogenase (LDH). Both patient groups received comparable curative intent therapy and showed comparable complete response rate precluding treatment differences as modifying outcome. Multivariate analysis indicated Ki-67 is an independent predictor of survival (multivariate P = .006). Further statistical analysis using only B-cell DLCL patients treated with CHOP (63 patients) indicated that Ki-67 greater than 60 retained strong prediction of poor outcome (P = .002, log-rank) among this homogeneous group. We conclude that high proliferative activity (Ki-67 greater than 60) is an independent factor allowing laboratory prediction of probable poor outcome of DLCL.


1992 ◽  
Vol 7 (2) ◽  
pp. 93-96 ◽  
Author(s):  
A. Benetti ◽  
A. Berenzi ◽  
P. Grigolato

We studied the growth fraction of55 resected colorectal adenocarcinomas by means of a three-step immunoperoxidase technique (avidin-biotin-peroxidase) using the monoclonal antibody Ki67 directed against a cell proliferation-associated nuclear antigen. The percentage of Ki67-positive cells was evaluated independently by two observers, and a Ki67 score was obtained for each case. No correlation was observed between Ki67 staining and patient's age and sex, tumor size and localization or grading and staging according to Dukes’ method (modified by Astler-Coller and Turnbull). The growth fraction showed extreme heterogeneity in the cases examined, within each grade of differentiation.


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