RAPID AND PROGNOSTICALLY VALID QUANTIFICATION OF IMMUNOHISTOCHEMICAL REACTIONS BY IMMUNOHISTOMETRY OF THE MOST POSITIVE TUMOR FOCUS - A PROSPECTIVE FOLLOW-UP-STUDY ON BREAST-CANCER USING ANTIBODIES AGAINST MIB-1, PCNA, ER, AND PR

The prognostic significance of immunohistochemical markers for cell pr oliferation [MIB-1, proliferating cell nuclear antigen (PCNA)I and hor mone receptor analysis [oestrogen receptor (ER), progesterone receptor (PR)] was tested by means of immunohistometry in a series of 103 brea st cancer patients in comparison with the lymph node status N, the tum our size T, histomorphological grading and the biochemical ER and PR s tatus. Immunohistochemical reactions mere performed on 2 mu m sections from paraffin-embedded tissue, using an indirect peroxidase method. T he proportion of immunostained tumour cell nuclei mas determined using a TV-image analysis system. Measurements were performed using a 20 x objective on 40 viewing fields (1.94 mm(2), MIB-1 and PCNA) or 20 view ing fields (0.97 mm(2), ER and PR). The mean immunopositivity of all v iewing fields and the value of the most immunopositive viewing field ( MIB-1(max), PCNA(max), PRmax, ERmax) mere calculated. The mean values and the maximal values mere highly correlated (r=0.903, P<0.001). Afte r 1:2:1 quantilization, 84.2 per cent of the 412 single measurements r evealed mean and maximal values in the same category (P<0.0001). For e ach of the four immunohistochemical markers, the prognostic significan ce of the maximal values was higher than that of the mean values. The highest prognostic significance mas found for MIC-1(max) (P=0.0002), f ollowed by PRmax (P=0.0046), ERmax (P=0.0154), and PCNA(max) (P=0.0161 ). From the results of a Cox model, a 'prognostic index (PI)' mas deve loped, ranging from -1 to 8: PI=2 x N+T+MIB-1(max)-PRmax. The four gro ups of patients with PI values of <2, 2-3, 4-5, and >5 revealed signif icantly different 7.5-year survival probabilities (P<0.0001). The simp licity of the PI makes it a clinically useful, routinely applicable, a nd understandable parameter in the surgical pathology of breast carcin oma. (C) 1998 John Wiley & Sons, Ltd.