Proliferation Activity in Pituitary Adenomas: Measurement by Monoclonal Antibody Ki-67

Neurosurgery ◽  
1989 ◽  
Vol 25 (6) ◽  
pp. 927-930 ◽  
Author(s):  
Engelbert Knosp ◽  
Klaus Kitz ◽  
Axel Perneczky
Keyword(s):  
Monoclonal Antibody ◽  
Pituitary Adenomas ◽  
Direct Determination ◽  
Nuclear Antigen ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Histological Techniques ◽  
Cytological Smear ◽  
Significant Difference ◽  
Proliferation Activity

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.

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 ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Pituitary Adenomas ◽  
Apoptotic Index ◽  
Antiproliferative Effect ◽  
Nuclear Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Growth Fraction ◽  
Ki 67 ◽  
Significant Difference ◽  
Octreotide Treatment

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.

Ki-67 Labeling Index in Breast Cancer

1989 ◽  
Vol 75 (6) ◽  
pp. 557-562 ◽  
Author(s):  
Sergio Crispino ◽  
Ambrogio Brenna ◽  
Daniela Colombo ◽  
Bajardo Flores ◽  
Silvestro D'Amico ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Monoclonal Antibody ◽  
Menopausal Status ◽  
Mitotic Rate ◽  
Labeling Index ◽  
Nuclear Antigen ◽  
Proliferating Cells ◽  
Cell Cycle Kinetics ◽  
Ki 67

Measurements of cell cycle kinetics have been found to correlate with the clinical course of patients with breast cancer. However, the thymidine labeling index and more rapid methods like flow cytometry remain complicated and costly. We assessed cell proliferation of 67 breast carcinomas by an immunoperoxidase procedure using a monoclonal antibody, Ki-67, which reacts with a nuclear antigen in proliferating cells. The percentage of Ki-67 positive cells ranged from 2% to 70 %. Tumors with high mitotic rate, high nuclear grade, high histologic grade, and negative estrogen receptors had statistically higher Ki-67 labeling rates. We found no significant differences between the Ki-67 labeling rate and other clinical (age at diagnosis, menopausal status) or pathologic (necrosis, fibrosis, vascular invasion, lymphatic invasion, cellular reaction, tumor size, lymph node metastases) features assessed. These results parallel previously reported data, and confirm that this immunohistochemical staining of breast carcinoma by Ki-67 monoclonal antibody can be considered a rapid and convenient method for assessing cell cycle kinetics. However, further studies, evaluating the correlation between Ki-67 labeling rate and prognosis are needed to better define the real usefulness of this analysis in clinical practice.

Growth rate of human pituitary adenomas

1987 ◽  
Vol 67 (6) ◽  
pp. 803-806 ◽  
Author(s):  
Alex M. Landolt ◽  
Taichiro Shibata ◽  
Paul Kleihues
Keyword(s):  
Pituitary Adenomas ◽  
Growth Characteristics ◽  
Nuclear Antigen ◽  
Growth Fraction ◽  
Proliferating Cells ◽  
Human Pituitary ◽  
Ki 67 ◽  
Content Type ◽  
Biopsy Specimens

✓ 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.

scholarly journals Evolutionary conservation in various mammalian species of the human proliferation-associated epitope recognized by the Ki-67 monoclonal antibody.

1989 ◽  
Vol 37 (10) ◽  
pp. 1471-1478 ◽  
Author(s):  
B Falini ◽  
L Flenghi ◽  
M Fagioli ◽  
H Stein ◽  
R Schwarting ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cell Proliferation ◽  
Mammalian Species ◽  
Calf Serum ◽  
Evolutionary Conservation ◽  
Resting Cells ◽  
Nuclear Staining ◽  
Proliferating Cells ◽  
Ki 67

The human proliferation-associated epitope recognized by the Ki-67 monoclonal antibody (MAb) was detected in proliferating normal and neoplastic cells of many mammalian species (lamb, calf, dog, rabbit, rat) besides human. In contrast, Ki-67 stained proliferating cells from other species weakly (mouse) or not at all (swine, cat, chicken, pigeon). The immunostaining pattern of Ki-67 in animal tissues was identical to that previously described in human: Ki-67 reacted only with cells known to proliferate (e.g., germinal center cells, cortical thymocytes) but not with resting cells (e.g., hepatocytes, brain cells, renal cells); this MAb produced a characteristic nuclear staining pattern (e.g., stronger labeling of nucleoli than of the rest of the nuclei and staining of chromosomes in mitotic figures); and Ki-67 crossreacted with the squamous epithelium in both animal and human tissues. In vitro studies showed that when quiescent (Ki-67-negative) NIH 3T3 fibroblasts or bovine peripheral blood lymphocytes were induced to proliferate, the appearance of Ki-67-positive cells paralleled the induction of cell proliferation caused by addition of fetal calf serum or PHA, respectively, to the cultures, and in both human and rat proliferating cells the Ki-67 expression closely paralleled the incorporation of [3H]-thymidine. These findings indicate that the epitope recognized by the Ki-67 MAb in human and animal species is the same. The widespread evolutionary conservation of the human proliferation-associated epitope recognized by the Ki-67 MAb suggests that it and/or its carrier molecule may play an important role in regulation of cell proliferation.

Residual nonfunctioning pituitary adenomas: prognostic value of MIB-1 labeling index for tumor progression

2009 ◽  
Vol 111 (3) ◽  
pp. 563-571 ◽  
Author(s):  
Georg Widhalm ◽  
Stefan Wolfsberger ◽  
Matthias Preusser ◽  
Ingeborg Fischer ◽  
Adelheid Woehrer ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Pituitary Adenomas ◽  
Residual Tumor ◽  
Labeling Index ◽  
Ki 67 ◽  
Nonfunctioning Pituitary Adenomas ◽  
Time Period ◽  
Tumor Group ◽  
Significant Difference ◽  
Mib 1

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).

The monoclonal antibody Ki-67 as a marker for proliferating cells in stereotactic biopsies of brain tumours

1987 ◽  
Vol 89 (3-4) ◽  
pp. 117-121 ◽  
Author(s):  
C. B. Ostertag ◽  
B. Volk ◽  
T. Shibata ◽  
P. Burger ◽  
P. Kleihues
Keyword(s):  
Monoclonal Antibody ◽  
Brain Tumours ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Stereotactic Biopsies

scholarly journals Proliferating cell nuclear antigen (PCNA) expressed in human leptomeninges.

1996 ◽  
Vol 44 (11) ◽  
pp. 1261-1265 ◽  
Author(s):  
H Funato ◽  
M Yoshimura ◽  
Y Ito ◽  
R Okeda ◽  
Y Ihara
Keyword(s):  
Monoclonal Antibody ◽  
Cell Proliferation ◽  
Smooth Muscle ◽  
Proliferating Cell Nuclear Antigen ◽  
Normal Subjects ◽  
Nuclear Antigen ◽  
Ependymal Cells ◽  
Ki 67 ◽  
Proliferating Cell ◽  
Strong Immunoreactivity

Here we report on the presence of proliferating cell nuclear antigen (PCNA) in human leptomeninges from 35 normal subjects with ages ranging from 57 to 94 years. Strong immunoreactivity with PC10 (a monoclonal antibody to PCNA) was detected in the nuclei of meningothelial cells, smooth muscle cells of leptomeningeal vessels, and ependymal cells. An immunoblot of leptomeningeal homogenate with PC10 showed the presence of a single band at 35 KD, the expected molecular mass of PCNA. Ki-67, another marker for cell proliferation, was undetectable in human leptomeninges. These observations point to isolated PCNA expression in tissue in which cells are not actively proliferating.

Expression of Ki-67 antigen in nonfunctioning pituitary adenomas: correlation with growth velocity and invasiveness

2003 ◽  
Vol 99 (4) ◽  
pp. 674-679 ◽  
Author(s):  
Jürgen Honegger ◽  
Carsten Prettin ◽  
Friedrich Feuerhake ◽  
Manfred Petrick ◽  
Jürgen Schulte-Mönting ◽  
...  
Keyword(s):  
Growth Rate ◽  
Growth Velocity ◽  
Pituitary Adenomas ◽  
Growth Potential ◽  
Nuclear Antigen ◽  
Ki 67 ◽  
Content Type ◽  
Nonfunctioning Pituitary Adenomas ◽  
Invasive Behavior ◽  
Fine Print

Object. The cell cycle—dependent nuclear antigen Ki-67 is related to growth potential in a variety of tumors. Elevated expression of Ki-67 was previously shown in recurrent pituitary adenomas; however, it has remained unclear whether this expression is related to the growth velocity or invasive behavior of these tumors. The aim of this study was to determine the correlation of Ki-67 antigen expression, growth velocity, and invasiveness in nonfunctioning pituitary adenomas. Methods. Between April 1998 and April 2002, 23 patients with nonfunctioning pituitary adenomas who had participated in an observation period in which multiple computerized tomography and magnetic resonance imaging studies had been performed were surgically treated in our department. Tumor volumes were assessed using a stereological method based on the Cavalieri principle. The growth rate was calculated for each patient. Expression of Ki-67 antigen was examined using the monoclonal antibody MIB-1. The assessed growth velocity of the adenomas was best described by a linear growth model. The correlation between Ki-67 expression and growth rate was highly significant. Rapidly growing adenomas (>0.07% daily increase in size) were found to have a Ki-67 labeling index (LI) exceeding 1.5%, whereas all five adenomas with a very slow growth rate (< 0.02% daily increase in size) had a Ki-67 LI lower than 1.5%. No correlation was found between the growth rate and the invasive character of the adenomas. Conclusions. Expression of Ki-67 antigen is significantly correlated to the growth velocity of pituitary adenomas. Invasive behavior is a feature independent of proliferative activity. The extent of Ki-67 expression is helpful for clinical decision making and routine assessment of Ki-67 is recommended during the histopathological workup of pituitary adenomas.

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