Simultaneous immunohistochemical and biochemical hormone receptor assessment in breast cancer provides complementary prognostic information.

The prognostic value of the biochemical and the immunohistochemical assessment of estrogen- and progesterone receptor (ER, PR) status was tested in 111 breast cancer patients, mostly focusing on whether the results reveal complementary prognostic information. The biochemical receptor analysis was performed on snap-frozen tumor tissue using a standard protocol (ER-DCC, PR-DCC). The immunohistochemical staining was done on 4 microns thick paraffin sections and was evaluated semiquantitatively (ER-IHC, PR-IHC) and immunohistometrically by means of image analysis (ERMEAN, PRMEAN). 74% of the ER-DCC and 50% of the PR-DCC assays were interpreted as positive. The positivity rates of the immunohistochemical reactions ranged between 78% and 81% for ER and between 66% and 82% for PR, depending on the interpretation mode. The concordance rate for the DCC method was 68%, and ranged between 77% and 85% for the immunohistochemical results on paraffin sections. ER-DCC and PR-DCC showed a better survival for receptor-positive patients; however, this tendency was only statistically significant for the PR-DCC (p = 0.0294). Patients with immunohistochemically determined ER- or PR-positivity revealed a significantly better survival than receptor-negative patients, the effect being stronger for the progesterone receptor (ER: p = 0.0253, PR: p = 0.0005). Combining the different methods and receptors in a multivariate analysis, we observed that a) ER and PR reveal complementary prognostic information to each other after immunohistochemical determination (p < or = 0.0018) and that, b) complementary prognostic information was also obtainable by comparing the biochemical and the immunohistochemical PR-analysis (p < or = 0.0084); slightly more significant results were obtained for ERMEAN and PRMEAN compared to ER-IHC and PR-IHC. Considering the lymph node status and a combined receptor analysis (PR-DCC, ERMEAN, PRMEAN) as the two strongest prognosticators in multivariate Cox models, the combined receptor analysis was able to discover for each of the three groups of NO- and N1-patients different survival probabilities (p < 0.0001). In conclusion, the ER-DCC appears to be dispensable in all patients. In lymph node-negative patients, the PR-DCC has no outstanding merit, indicating that the neccessity of this method is also controversial. In priamry tumors of lymph node-positive patients, however, all three remaining types of receptor analysis should be evaluated for their therapeutic implications.

Interobserver reproducibility of immunocytochemical estrogen- and progesterone receptor status assessment in breast cancer.

The interobserver reproducibility in the immunocyto-chemical assessment of estrogen- and progesterone receptor status was investigated in a series of 102 cases of primary breast carcinomas. Immunostaining was performed on 4 microns cryostat sections using estrogen- and progesterone immunocytochemical assays (ER-ICA and PR-ICA) with methylgreen counterstaining. The slides were evaluated independently by two observers. The proportion and staining intensity of ER- or PR-positive tumor cells in areas of invasive tumor growth was subjectively assessed based on the examination of the entire slide. Scoring was performed according to the proposals of Remmele and Reiner. Additionally, the cytosol estrogen- and progesterone receptor content was determined by a standard dextran-coated charcoal (DCC-) assay. Observer 1 interpreted 60 (59%) of the ER-stained specimens and 50 (49%) of the PR-stained specimens as receptor-positive; for observer 2 the respective values were 59 (58%) for ER-stained specimens and 51 (50%) for PR-stained specimens. Positive biochemical receptor status was found in 68 cases with the ER-DCC (67%) and in 47 with the PR-DCC (46%). The interobserver agreement between the two observers on the immunocytochemical receptor status was 89% for the estrogen receptor and 93% for the progesterone receptor 8.8% of the specimens were interpreted differently. Using the Remmele score, the concordance within the group of cases, which had been interpreted as receptor-positive by both observers, was 54% for the estrogen receptor and 57% for the progesterone receptor. The Reiner score showed concordant scorings of 72% for the estrogen receptor and 79% for the progesterone receptor. The present study indicates that complete agreement between scorings of different observers may not be expected, mainly due to differences in the interpretation of the specificity of staining and of the histological structures after immunostaining. The concordance of positive results using the three-graded Reiner score is comparable to that of the three-graded Bloom and Richardson grading system of breast cancer and reflects the limitation of subjective evaluation of morphology in general.