INTESTINAL TREFOIL FACTOR (TFF-3) AND PS2 (TFF-1), BUT NOT SPASMOLYTIC POLYPEPTIDE (TFF-2) MESSENGER-RNAS ARE COEXPRESSED IN NORMAL, HYPERPLASTIC, AND NEOPLASTIC HUMAN BREAST EPITHELIUM

pS2-TFF 1 is expressed in breast cancers and has been investigated as a potential prognostic factor reflecting oestrogen dependence. The rel ationship to the expression of other trefoil peptides, human spasmolyt ic polypeptide (hSP-TFF 2) and intestinal trefoil factor (hITF/hPI.B-T FF 3) is documented here, Fifty-seven breast specimens were selected f rom surgical pathology archives and included five normal breasts (two lactating), seven benign proliferative lesions, 11 ductal carcinomas i n situ (DCIS), three lobular carcinomas in situ (LCIS), 24 invasive du ctal carcinomas (IDC), and seven invasive lobular carcinomas (ILC), Th e comparative distribution of trefoil mRNAs was assessed by in situ hy bridization using S-35-labelled riboprobes and immunohistochemical sta ining for pS2-TFF 1 and hSP-TFF 2. pS2-TFF 1 and hITF/hPI.B-TFF 3 mRNA were focally present at low signal intensity in normal and benign bre ast. Both pS2-TFF 1 and hITF/hPI.B-TFF 3 were expressed in all DCIS, L CIS and ILC, and 21/24 IDC, Overall, expression patterns of pS2-TFF 1 and hITF/hPI.B-TFF 3 coincided, but hITF/hPI.B-TFF 3 mRNA was usually found in a greater proportion of cells. Expression of hSP-TFF 2 peptid e or mRNA was not detected in any of these cases. MCF 7 breast carcino ma cells also expressed hITF/hPI.B-TFF 3 and pS2-TFF 1 mRNAs but not h SP-TFF 2. hITF/hPI.B-TFF 3 co-expression with pS2-TFF 1 may act as a p rognostic factor, but also raises questions about the regulatory pathw ay for pS2-TFF 1 hITF/hPI.B-TFF 3. Trefoil factors have effects on cel l motility and spreading in vitro, and co-expression of hITF/hPI.B-TFF 3 with pS2-TFF 1 could be functionally significant if they form a het erodimer or compete for receptor binding. Absence of hSP-TFF 2 express ion may be of equal relevance to tumour cell biology. (C) 1997 by John Wiley & Sons, Ltd.