PROTEIN-TYROSINE-PHOSPHATASE ACTIVITY AS A DIAGNOSTIC PARAMETER IN BREAST-CANCER

Cellular phosphotyrosine levels are regulated by the balance between p rotein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs ). It is supposed that this balance is disturbed in tumour cells, maki ng the increased or altered activity of PTKs and PTPs likely hallmarks of tumour tissues. Indeed it could be shown that the PTK activity was increased in breast cancer in correlation with prognosis (Hennipman e r al, Cancer Res. 49, 516-522, 1989). In the present report we measure d the PTP activities in breast cancer and normal breast tissues. An in crease of approximately three- to four-fold was measured in the cytoso lic tumour fractions compared to normal, whereas the solubilized membr ane fraction PTP activity showed an increase in tumours of approximate ly 1.5-fold. Remarkably, the membrane PTP activity correlated with the presence of tumour positive axillary lymph nodes (p = 0.004), whereas the cytosolic PTP activity correlated with the mitotic index, a highe r PTP activity occurring when the mitotic index was higher than 10 (p = 0.0004). These results indicate that membrane PTP activity may be co nsidered as an index of metastatic potential, whereas cytosolic PTP ac tivity may be a measure of the growth capacity of the tumour. The incr ease of PTP activity in breast cancers was confirmed by enzyme-histoch emical studies. In frozen sections of tumours a strong to moderate act ivity was found in both tumour cells and interstitial cells. In the in terstitium membrane activity was most pronounced, whereas in the tumou r cells diffuse staining of the cytoplasm together with a clear membra ne staining was demonstrated. Immunoblotting with anti-phosphotyrosine antibodies also reveals differences between the tumours and normal ti ssues, confirming the disturbance of the balance between protein tyros yl phosphorylation and dephosphorylation in the tumour cells.