Expression of caspases 3, 6 and 8 is increased in parallel with apoptosis and histological aggressiveness of the breast lesion

The aim of this investigation was to study the expression of caspases 3, 6 and 8 and their association to apoptosis in preneoplastic and neoplastic le sions of the breast. The material consisted of nine benign breast epithelia l hyperplasias, 15 atypical hyperplasias, 74 in situ and 82 invasive carcin omas. The extent of apoptosis was assessed by the TUNEL method and caspase 3, 6 and 8 expression by immunohistochemistry with specific antibodies. Inc reased caspase 3 immunopositivity, as compared to staining of normal breast ductal epithelium, was seen in 22% of benign epithelial hyperplasias, 25% of atypical hyperplasias, 58% of in situ carcinomas and 90% of invasive car cinomas. The corresponding percentages for caspase 6 and 8 were 11%, 25%, 6 0%, 87% and 22%, 57%, 84%, 83% respectively. In high-grade in situ lesions there were significantly more cases with strong caspase 3, 6 and 8 immunore activity than in low- and intermediate-grade lesions (P = 0.0045, P = 0.049 and P = 0.0001 respectively). In invasive carcinomas, however, no associat ion between a high tumour grade and caspase 3, 6 or 8 expression was found (P = 0.27; P = 0.26 and P = 0.69 respectively). The mean apoptotic index wa s 0.14 +/-: 0.14% in benign epithelial hyperplasias, 0.17 +/- 0.12% in atyp ical hyperplasias, 0.61 +/- 0.88% in in situ carcinomas and 0.94 +/- 1.21% in invasive carcinomas. In all cases strong caspase 3, 6 and 8 positivity w as significantly associated with the extent of apoptosis (P < 0.001, P = 0. 015 and P = 0.050 respectively). The results show that synthesis of caspase s 3, 6 and 8 is up-regulated in neoplastic breast epithelial cells in paral lel to the increase in the apoptotic index and progression of the breast le sions. (C) 1999 Cancer Research Campaign.