Prolaction As A Local Growth Promoter In Patients With Breast Cancer

The purpose of this study was to find out the clinical utility of PRL in patients with early and advanced breast cancer. Patients with stage II and stage III disease were followed for a period of 5 and 3 years, respectively or until death within the stipulated time. Circulating PRL was assayed preoperatively and sequentially threrafter from III patients with breast cancer. Immunohistochemical localisation of PRL and PRLR was performed on formal in fixed, paraffin embedded tissue sections. Tumoral PRLR was estimated by ligand binding assay, and expression of PRL mRNA and PRLR mRNA was carried out by RTPCR. Further, the RTPCR PRL amplimer was sequenced. Expression of PRL isoforms in serum and cytosol samples was studied. Hyperprolactinemia (PRL>20.0 ng/ml serum) was observed in 58% of the breast cancer patients. Univariate analysis showed that patients with hyperprolactinemia had a significantly shorter overall survival than patients with PRL <20.0 ng/ml serum (P = 0.0001). Similar results were observed when patients were grouped according to disease stage. Changes in serial PRL levels showed excellent correlation with response to therapy and progression of disease, and accurately indicated the response and development of resistance to TAM in these patients. Seventy eight percent of the tumors showed positive immunoreactivity with PRL antibody. PRL mRNA expression was seen in 52% of the tumors. Sequence analysis of the 234 bp PRL amplimer revealed that the sequence was homologous to the sequence of exon 5CR PRL transcript in breast tumors. mRNA. Western hybridization showed the presence of three isoforms of PRL protein in serum and tumor cytosols of breast cancer patients. The action of PRL is mediated by PRLR and it was observed that the PRLR positivity by ligand binding assay was 23% where as with immunohistochemistry the positivity was 80%. The expression of PRLR mRNA by RT-PCR showed two forms of PRLR mRNA i.e. the long form (800-900 bp), seen in 22% of the tumors and the intermediate forms of (500-600 bp), seen in 54% of the tumors. This multifaceted study of PRL suggests that breast cancer cells produce PRL and this ectopically produced PRL might be acting as a major local growth promoter via autocrine and paracrine mechanisms. It may provide new insights into endocrine treatment of breast cancer.