DIFFERENTIAL IMMUNOHISTOCHEMICAL DETECTION OF TRANSFORMING GROWTH-FACTOR-ALPHA, AMPHIREGULIN AND CRIPTO IN HUMAN NORMAL AND MALIGNANT BREAST TISSUES

The expression of growth factors, such as transforming growth factor a lpha (TGF alpha), amphiregulin (AR) and CRIPTO, a type-1 tyrosine-kina se growth factor receptor (erbB-2), and a tumor-suppressor gene (P53), that have been implicated in the development and/or the progression o f breast cancer, was evaluated by immunohistochemistry in 100 human pr imary infiltrating breast carcinomas (IBC). AR and CRIPTO immunoreacti vity was also assessed in 55 human breast ductal carcinomas in site (D CIS). Within the 100 IBC, 80, 50, 73, 17, and 34 tumors expressed mode rate to high levels of TGF alpha, AR, CRIPTO, erbB-2, and p53 respecti vely. In addition, AR and CRIPTO immunoreactivity were found in 11 and in 26 out of 55 DCIS respectively. In contrast, only 4, 3, and 2 out of 10 normal mammary-gland samples were weakly positive for TGF alpha AR, and CRIPTO expression, respectively, whereas none was positive for erbB-2 or p53. Within the 100 IBC, expression of erbB-2 significantly correlated with high histologic and nuclear grading, with high growth fraction, and with estrogen-receptor(ER)- and progesterone-receptor(P gR)-negative tumors. A statistically significant correlation was also observed between p53 expression and high histologic grading, high grow th fraction, and PgR-negative tumors. In contrast, no significant corr elations were found between TGF alpha, AR, and CRIPTO immunoreactivity and various clinicopathological parameters, with the exception of a p ositive correlation between TGF alpha and ER expression. These data de monstrate that TGF alpha AR, and CRIPTO expression are significantly i ncreased in malignant mammary epithelium relative to normal epithelium . In particular, the differential expression of CRIPTO may serve as a potential tumor marker for breast carcinogenesis. (C) 1996 Wiley-Liss, Inc.