Messenger RNA determination of estrogen receptor, progesterone receptor, pS2, and plasminogen activator inhibitor-1 by competitive reverse transcription-polymerase chain reaction in human breast cancer.

Estrogen receptor (ER), progesterone receptor (PR), the estrogen-inducible protein pS2, and plasminogen activator inhibitor-1 (PAI-1) are important prognostic factors in primary breast cancer. The protein concentrations of these factors in breast tumors have been well documented. However, few data about the mRNA expression of ER, PR, pS2, and PAI-1 in breast cancer are available, which is mostly due to the limitations of conventional techniques for mRNA analysis. We have described a competitive reverse transcription-PCR system for the simultaneous quantification of ER, PR, pS2, and PAI-1 mRNA in tumor samples. Here, we evaluated 100 tumor biopsies from breast cancer patients for the mRNA expression of ER, PR, pS2, and PAI-1. The results were analyzed for correlations with protein status and with clinical data. Significant correlations between mRNA expression levels and protein concentrations of all tested markers were found. In only a few cases was there an obvious discordance between the measurable amounts of mRNA and protein, especially for ER and PR. In addition, ER, PR, and pS2 mRNA levels correlated significantly with each other. No correlation between PAI-1 mRNA amount and the expression of the other markers was found. With respect to clinical data, ER and PR mRNA levels were found to be inversely correlated to tumor size and histological grade but not to the lymph node status. pS2 and PAI-1 mRNA expression were not correlated with tumor size, grade, or lymph node involvement. In conclusion, competitive reverse transcription-PCR may be used as an alternative for the study of prognostic factors in human breast cancer and other malignancies. However, before mRNA expression is measured for diagnostics, a presumed concordance of mRNA and protein expression must be evaluated very carefully for every gene.