THE NEU-ONCOGENE PRODUCT IN SERUM AND TISSUE OF PATIENTS WITH BREAST-CARCINOMA

Background: A soluble 105 kD neu-related protein is detectable in conditioned medium from breast cancer cells expressing the neu-oncogene product and in serum of nude mice bearing tumors that overexpress neu-oncogene. Patients and methods: In 100 patients with primary (n = 33) relapse-free (n = 6) and metastatic (n = 61) breast carcinoma the serum levels of the soluble neu-related protein were investigated by ELISA techniques. Median age was 57 years, range 26-89 years. Results: The neu-protein serum levels were below 40 HNU/ml (human neu-antigen unit) in 72 patients and 40 or more HNU/ml in 28 patients. In 30 patients with primary breast carcinoma, tested before mastectomy, all serum-neu-protein samples were negative. However, 26 of 61 metastazised patients (43%) were serum-neu-protein-positive. In disseminated disease (n = 61), serum-neu-protein-positivity was more likely to be seen in patients with visceral metastases (18/33 = 54%), than in patients with nonvisceral metastases (8/28 = 28%). Furthermore, monitoring of the serum-neu-protein levels reflected clinical course. For 53 patients original paraffin-embedded tumor material was available for studying immunohistochemical neu-protein expression. In 39/53 (73%) patients immunohistochemical and ELISA data showed corresponding results. In 27/30 (90%) patients, from whom sera and tissue could be obtained at the same time at primary mastectomy, results of immunohistochemistry in primary tumor and serum ELISA were negative and mutually confirmatory. However, the other three patients were positive for immunohistochemical neu-protein expression in primary tumor but negative for serum-neu-protein expression. Conclusions: Our results suggest that patients with advanced breast cancer and an elevated serum-neu-protein level may have a poor clinical outcome. This test might be a useful tool for monitoring patients with advanced breast carcinoma, but not those with early disease. Further prospective studies are warranted to elucidate the question of whether this test can contribute to determining prognosis and treatment strategies.