Biochemical correlates of morphologic differentiation in human breast cancer.

: In 115 breast carcinoma tissues, histologica grade and cell cytosol concentrations of estrogen receptor (ER) and progesterone receptor (PR) and two breast cyst fluid proteins (gross cystic disease fluid protein [GCDFP-15] and nonreceptor progesterone-binding protein [PBP]) were deterMined. Higher levels (expressed as femtomoles per milligram of protein) of ER (128 +/- 28 versus 11 +/- 1, P less than 0.001) and PR (82 +/- 16 versus 3 +/- 1, P less than 0.001) were found in grade 1 (well-differentiated) carcinomas as compared with grade 3 (poorly differentiated) carcinomas. Similarly, higher concentrations (expressed as nanograms per milligram of cytosol protein) of GCDFP-15 (2110 +/- 840 versus 210 +/- 40, p less than 0.001) and PBP (4920 +/- 1200 versus 370 +/- 60, P less than 0.001) were found in grade 1 as compared with grade 3 carcinomas. Tumor cytosols that contained low levels of both cyst proteins (less than 225 ng/mg GCDFP-15 and less than 750 ng/mg PBP) had a high incidence of grade 3 (35 of 46, 78%) or grade 2 (15 of 46, 33%) histologic findings and had a high incidence of receptor-negative specimens (27 of 52, 52%). Based on these cutoff levels, grade 2 lesions were subdivided into a "high" cyst protein group, which had ER and PR levels similar to grade 1 tumors (93.1 +/- 26.7 for ER and 84.7 +/- 32.4 for PR, P greater than 0.3), and a "low" group, which had receptor values similar to grade 3 carcinomas (14.1 +/- 5.3 for ER and 9.1 +/- 5.2 for PR, P less than 0.3). Although the mean cytosol content of carcinoembryonic antigen (CEA) was significantly higher in malignant tissues (125 +/- 27 ng/mg cytosol protein) than in benign tissues (4.8 +/- 1 ng/mg cytosol protein), the CEA content was not significantly different between grades 1 and 3 tumors.