John Pearson

Prospective assessment of the role of five tumour markers in breast cancer

SummaryRetrospective analysis previously identified significant elevation of five tumour markers, carcinoembryonic antigen (CEA), ferritin, orosomucoid,C-reactive protein and erythrocyte sedimentation rate (ESR), in patients with systemic breast cancer and showed that changes in each of these markers individually correlated significantly with therapeutic response. In this study we have prospectively tested these findings. None of the five markers was significantly elevated in primary breast cancer compared to normal control or benign breast disease groups. They therefore appear to have no role either in screening or in the differential diagnosis of breast cancer. There was a significant elevation of all five markers in patients with systemic breast cancer (P <0.0001; analysis of variance) but sequential changes in CEA and ESR only correlated significantly with the UICC-assessed response. Prospective confirmation of the correlation between changes in serum CEA and ESR provides the basis for using these markers in the assessment of response to therapy in patients with systemic breast cancer.

Assessment of four monoclonal antibodies as serum markers in breast cancer

Four monoclonal-antibody-defined serum markers (CA15-3, HMFG1, HMFG2 and NCRC-11) were examined in five groups of subjects: controls, benign breast disease and stage I/II, stage III and metastatic breast cancer. None of the markers were significantly elevated in primary breast cancer (i.e. stage I/II or stage III) compared with controls or patients with benign breast disease. These markers therefore have no role in screening or in the diagnosis of primary breast cancer. CA15-3, HMFG2 and NCRC-11 were significantly increased in the patients with metastatic breast cancer (P less than 0.001), indicating a potential use in the diagnosis of symptomatic metastases. In patients with metastases, sequential changes in CA15-3 correlated significantly with clinical response to therapy. Thus CA15-3 is a powerful marker of response and in combination with other markers, may provide an objective measurement of response to therapy in patients with advanced breast cancer.

Noncytolytic extraction of soluble antigens from leukemic blast cells (L2C-EN)

SummaryLithium 3,5 diiodosalicylate (LIS), a chemical utilized for the noncytolytic extraction of cell surface antigens, was used in this study to extract glycoproteins from the cell membranes of L2C-EN leukemic blast cells. The crude soluble antigen (LIS-L2C) preparation was found to confer immunoprotection in syngeneic guinea pigs against a lethal challenge of L2C-EN. Titration of the crude LIS-L2C soluble antigen extract revealed that 1 mg antigen gave 100% protection against a 2×105 viable tumor cell challenge 2 weeks after immunization and that immunizing doses of 0.1 mg, 0.25 mg, and 0.5 mg soluble antigen afforded 17%, 66%, and 83% protection, respectively. The specificity of this immune response was demonstrated by the failure of guinea pigs immunized with 1 mg LIS extract prepared from another guinea pig tumor (line 10 hepatoma) to be refractory to a similar L2C tumor cell challenge. A cell-mediated immune response to the LIS-L2C soluble antigen was observed in animals, based on a positive delayed hypersensitivity response to the soluble antigen 5 weeks after immunization. Similarly, in vitro testing revealed a specific blastogenic recognition of the soluble antigen by immune leukocytes.