Up-regulation of stress inducible MICA on high-grade breast carcinomas

Z Madjd MD^a, SE Pinder MD^b, PhD Spendlove^a, R Moss BSc^a, S Bevin MSc^a, LG Durrant PhD^a

^aCRC Clinical Oncology, ^bDept. of Histopathology; University of Nottingham, City Hospital, Nottingham, United Kingdom

Aim: The aim of this study is to investigate the expression of MICA on a well characteristic series of breast tissue arrays and its association with prognostic factors. MICA , is a stress –induced antigen which identified as an activator of both natural killer and T cells via interaction with their receptor NKG2D. Methods: A large set of samples (530) from patients with primary operable breast cancer with 15 years follow up were included in the present study. Tumour specimen from these patients who diagnosed between 1987 and 1992 had previously been included in tissue microarrays. The prognostic significance of MICA was then investigated in these tumours employing a rabbit polyclonal anti -MICA that we raised against a synthetic peptide and a standard immunohistochemistry method. Results: 97% of breast tumours showed cytoplasmic expression of MICA in tumour cells which was contrasted by the absence of staining of stroma . Expression of MICA was significantly associated with histological grade (p<0.05), lymph node stage (p<0.05), Nottingham Prognostic Index (p<0.05), vascular invasion (p<0.05) and type of tumours (p<0.05).Upregulation of MICA was more often found in high grade (G3), poor prognosis (NPI>5.4) tumours compared to well differentiated tumours. Conclusion: Our results suggest that an induced expression of MICA may be an indicator of poor prognosis for breast carcinoma. Further analysis of HLA class I and NKG2D expression in these breast microarrays will complete the role of interaction of these molecules in tumour prognosis.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 893 (Molecular pathology).