31P-NMR spectroscopy and histological studies of the response of rat mammary tumours to endocrine therapy

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Abstract
We have shown by 31P-NMR spectroscopy that ovariectomy, in N-methyl-N-nitrosourea induced mammary adenocarcinomas, increases signals from phosphocreatine (PCr) relative to nucleoside triphosphate (NTP) before measurable regression (2 days) and for at least a further 13 days. The present study correlates the NMR changes with histological changes in the regressing tumour. Mammary tumours were examined by NMR before, and 2 and 14 days after, ovariectomy or sham-ovariectomy. Sections were taken from five tumours at each time point after operation for histology and for immunocytochemical staining of myoepithelial cells, luminal cells and basement membrane material. The histology showed typical cribriform papillary type mammary adenocarcinomas. The luminal cell population had a high mitotic activity and there was a prominent myoepithelial layer. At 2 days post-ovariectomy no significant change in mitotic activity was observed and no cytological characteristics attributable to ovariectomy could be seen. At 14 days postovariectomy the tumour was indistinguishable from a tubular adenoma, had significantly reduced mitotic activity, a relative increase in myoepithelial cells and basement membrane material. The changes detected by NMR must reflect early metabolic events, perhaps related to the histological changes observed at 14 days after ovariectomy. 31P-NMR spectroscopy may permit early monitoring of endocrine therapy for mammary cancer.