The proliferative potential of human pituitary tumors in situ

Abstract

At the start of transsphenoidal microsurgery for removal of various types of pituitary adenomas, 21 patients received a 1-hour intravenous infusion of 5-bromodeoxyuridine (BUdR, 200 mg/sq m) to label tumor cells in the deoxyribonucleic acid (DNA) synthesis phase (S-phase). Excised tumor specimens were fixed in 70% ethanol and stained by the indirect peroxidase method using anti-BUdR monoclonal antibody as the first antibody. The percentage of BUdR-labeled cells, or S-phase fraction, was calculated for each specimen. The S-phase fraction was less than 0.1% in nine cases, 0.1% to 0.5% in seven, and greater than 0.5% in five. Except in two cases of Nelson's syndrome, in which it was greater than 1%, the S-phase fraction did not correlate with any other variable, including patient age, tumor size, or the duration of signs and symptoms. The small S-phase fraction of most of the pituitary adenomas correlates well with the clinical behavior of these tumors, which grow much more slowly than other kinds of brain tumors such as gliomas. However, the S-phase fractions varied by as much as one order of magnitude. The higher S-phase fractions may reflect aggressive and invasive growth. These results indicate that immunohistochemical studies of cell kinetics using BUdR and anti-BUdR monoclonal antibodies may provide information about the biological characteristics of pituitary adenomas which could lead to the design of appropriate treatment regimens (including surgery, radiation therapy, and chemotherapy) for individual patients.

The correlation of Ki-67 staining indices with tumour doubling times in regrowing non-functioning pituitary adenomas

“…Although there have been several studies on cell kinetics of pituitary adenomas [12,15,16,18,28], there has been no report about the correlation between the staining indices of cell cycle markers and tumour doubling times, and the difference of the staining indices of cell cycle markers between the regrowing and the cured cases. Now, immunocytochemistry using anti-Ki-67 monoclonal antibody (MIB-1) on paraffin embedded sections is available, which is expected to provide us with a new tool for measuring the proliferative potentials of brain tumours.…”

“…Studies of cell kinetics have proved to be useful in evaluating tumour progression and prognosing long term outcome in several types of tumours of the central nervous system [4,[16][17][18] and of other organs [31]. Although there have been several studies on cell kinetics of pituitary adenomas [12,15,16,18,28], there has been no report about the correlation between the staining indices of cell cycle markers and tumour doubling times, and the difference of the staining indices of cell cycle markers between the regrowing and the cured cases.…”

Proliferative potential in pituitary adenomas: Measurement by monoclonal antibody MIB-1

“…Most pituitary adenomas grow slowly and are considered benign [5,8,10,18,22]. Some, however, show aggressive [1] or invasive growth [18,19,26] and even metastases [9,24].…”

Cell kinetics in leukaemia and solid tumours studied with in vivo bromodeoxyuridine and flow cytometry

“…There are other rapidly progressing clinical studies with in vivo BUDR which employ FCM or immunohistochemistry for detecting the BUDR-labelled cells. They include very large series of AL and chronic myelogenous leukaemia (Raza et al, 1987), malignant and benign brain tumours (Cho et al, 1986;Hoshino et al, 1985, b Danova et al, 1988aNagashima et al, 1986), gastric (Dionigi et al, 1988;Danova et al, 1988b) and ovarian cancers (Erba & Mangioni, unpublished data) as well as miscellaneous tumours (Riccardi et al, 1988;Wilson et al, 1989). For solid neoplasias a long-discussed possibility is that kinetic parameters change in different areas of the tumour, so that the proliferative characteristics obtained may not be representative of overall tumour kinetics..…”