Robert D. E. Battersby

Cytogenetic studies in 50 meningiomas

In a series of 50 meningiomas, cytogenetic studies showed that almost half had a normal diploid karyotype. The remainder had monosomy 22, some with a normal diploid line also present. The initial monosomy was often followed by further chromosome loss, and occasionally by structural abnormalities, some with distinctive characteristics. Chromosomes most often involved in structural rearrangements were 1, 14, 10, and 19, and those most often lost were 17 and Y. The type of chromosome abnormalities seen were similar to those described for senescent human cell cultures, which suggests that common chromosomal mechanisms may be operative in benign tumors and senescent cells. Although meningiomas occur more commonly in females, the chromosomally abnormal tumors are distributed evenly between males and females. Within the group of tumors with structural chromosomal abnormality, there seems to be a bias toward meningotheliomatous histology, but otherwise the karyotype changes seen independent of the histologic type of tumor.

Long-term treatment of acromegaly with the somatostatin analogue SR-lanreotide

Objective: To assess the efficacy and tolerability of SR-lanreotide in the treatment of active acromegaly. Patients and design: 30 patients (17 men and 13 women) were treated in whom active acromegaly was confirmed by clinical features, a mean GH level of >5 mlU/l and failure to suppress GH to <2 mIU/l after a 75 g glucose load. Patients were treated for a median period of 60 weeks (range 12-168) with im injections of SR-lanreotide 30 mg given every 7-14 days. Measurements: Mean GH and IGF-I levels were measured at baseline and every 12-weeks together with symptom score assessment. MRI of the pituitary gland was performed at baseline and if an adenoma was identified at yearly intervals. Gall bladder ultrasound scans were performed at baseline and then every 24-weeks. Results: Twenty-three patients were treated for at least 48-weeks and, in these, GH levels fell from 10.5 mlU/l (7.6-17.6) (median and interquartile range) at baseline to 3.2 mIU/l (2.4-3.9) (p<0.0001) and IGF-I levels ftom 88.9 nmol/L (71.4-137.1) to 56.8 nmol/l (39.3-75.4) (p=0.0002). GH response to treatment was better in elderly patients (age≥65 years) compared to younger patients but neither sex, pre-treatment GH levels, previous surgery nor previous radiotherapy influenced the response. Treatment resulted in a significant improvement in the symptoms of active acromegaly in the majority of patients. A significant reduction in the size of the pituitary adenoma was documented in 6 of 10 patients who had a repeat MRI scan after one year. Treatment was well-tolerated by the majority of patients; side effects were mainly transient gastrointestinal symptoms. These were severe in only 2 patients necessitating discontinuation of the drug. Two patients developed new gall stones and 4 female patients had temporal hair loss necessitating stopping treatment in one of them. There were minor effects on glucose tolerance which were not of clinical importance. Conclusion: Long-term treatment of acromegaly with SR-lanreotide is effective in controlling GH and IGF-l levels and symptoms and is well tolerated in the majority of patients.

Mdm2 and the p53 pathway in human pituitary adenomas.

Studies on pituitary tumours have failed to identify mutations in the tumour suppressor gene p53 suggesting that the protein identified is wild type. p21WAF−1 is a downstream effector of p53 which promotes growth arrest. Mdm2 (mouse double minute) is a protein induced by wild type p53 and forms an autoregulatory feedback loop suppressing wild type p53 activity. The purpose of this study was to examine a group of pituitary tumours for expression of p53 and its two downstream effector proteins p21WAF−1 and mdm2 and to compare this with their radiological invasive status and proliferative potential as assessed by Ki‐67 expression.

Inherited multiple meningiomas: a clinical, pathological and cytogenetic study of an affected family.

The clinical features of a family with inherited multiple meningiomas as the major manifestation of neurofibromatosis are presented. The value of noninvasive radiological screening investigations is emphasised. The results of cytogenetic and pathological studies on the family are presented and discussed with a review of the relevant literature.

Cryostat section assay of oestrogen and progesterone receptors in meningiomas: a clinicopathological study.

Oestrogen receptors and progesterone receptors were measured in the cytosols from cryostat sections of 45 meningiomas from 40 patients (12 men, 28 women) using an isoelectric focusing technique. Near fascimile adjacent sections from the same tissue blocks were stained and examined to determine the histological subtype of the neoplasms. Appreciable levels of progesterone receptor (greater than 10 fmol/mg cytosol protein) were present in 24 (53.3%) of of the neoplasms, but no clinically important oestrogen receptor was detected in any of the tumours. Competitive binding studies on control tissue confirmed the specificity of the assay procedures. No correlation was found between progesterone receptor state and the age, sex, or menopausal state of the patients, or the histological subtype and site of the neoplasms. Four of the patients studied had multiple intracranial neoplasms, which in two were of differing progesterone receptor state. The presence of specific progesterone receptor in meningioma cytosols raises the possibility of hormonal manipulation in the treatment of this group of neoplasms.

Progesterone receptors in meningiomas: morphometric assessment of vascularity and cellularity on near facsimile cryostat sections.

Recently, there has been much interest in progesterone receptors (PR) in meningiomas,1 but although in breast cancer steroid hormone receptor status has been related to the cellularity of the neoplasm,2 no comparable study has been performed on meningiomas. Cryostat sections adjacent to sections assayed for PR from 45 meningiomas3 were stained with haematoxylin and eosin. Using a MOP-Videoplan (Kontron Electronic Group) image analysis system with digitising tablet, images of the sections were projected at a standard magnification on a television monitor and analysed for cellularity with respect to the neoplastic cell content (expressed as a percentage of the section area occupied by neoplastic cells) and vascularity (expressed as the percentage area of the section occupied by blood vessel profiles). No significant differences were found with respect to cellularity (Fig. I a) and vascularity (Fig. lb) between PR negative and PR positive neoplasms (p > 0 05, unpaired t test), although the neoplasms with the greatest vascularity (one haemangioblastic and two angiomatous meningiomas) were all found to be PR negative. According to the method of Underwood et al4 PR values were adjusted to compensate for differences in cellularity: