ESTROGEN-REGULATED GENES IN BREAST-CANCER - ASSOCIATION OF PLIV1 WITH LYMPH-NODE INVOLVEMENT

In order to isolate markers of oestrogen responsiveness in breast cancer, we have cloned a number of oestrogen-regulated genes. Two of these, pLIV1 and pLIV2 (pS2), have been shown to be predominantly expressed in oestrogen receptor (ER) + tumours. In this study, we examined their expression in relation to various clinical and histopathological features of breast cancer, and showed that pLIV1, but not pS2, is significantly associated with lymph node involvement (P < 0.01), while pS2 is more frequently observed in prememopausal patients (P < 0.05). Subdivision of the pLIV1 data by ER and nodal status of the tumour identified a highly significant association between pLIV1 expression and lymph node involvement in ER-positive disease, with 15/24 (63%) ER+ pLIV1+ tumours showing nodal involvement. Conversely, 20/23 (87%) ER+ pLIV1- patients were lymph node-negative (P < 0.001). Subdivision of the pS2 data by ER status did not reach significance. The application of pLIV1 as a marker of lymph node involvement was further exemplified in small tumours (much less than 2 cm), where 11/12 (92%) lymph node-positive patients expressed pLIV1, while 17/22 (77%) node-negative patients were pLIV1 negative (P < 0.001). Similarly, pLIV1 expression identified lymph node involvement in moderately differentiated tumours (P < 0.01), but was independent of vascular invasion. pLIV1 may, therefore, represent a candidate gene for metastatic spread in ER+ breast cancer.