Background: Immunohistochemistry for estrogen receptor may be used to distinguish metastatic breast cancers from adenocarcinomas of other sites, including those of the lung. The estrogen receptor exists as 2 subtypes, alpha and beta. Estrogen receptor alpha is the predominant subtype expressed by more than two-thirds of human breast cancers. Adenocarcinomas of lung origin may also express estrogen receptor, primarily the beta subtype. Human estrogen receptor alpha is highly homologous to estrogen receptor beta and consequently, antibodies used to detect estrogen receptor alpha in breast carcinomas may detect estrogen receptor beta in pulmonary adenocarcinomas. We investigated the immunohistochemical expression of estrogen receptor in proven primary lung adenocarcinomas using 3 anti-estrogen receptor alpha antibodies: mouse monoclonal 1D5, 6F11, and rabbit monoclonal SP1.
Design: Ninety-two pulmonary adenocarcinomas (53 women and 39 men) confirmed by clinical presentation and positive immunohistochemistry for thyroid transcription factor-1 (TTF-1) were included in this study. There were 19 incisional biopsies and 73 excisional specimens. Immunohistochemistry for estrogen receptor using antibodies 1D5, 6F11, and SP1 was performed on formalin-fixed, paraffin-embedded tissue following antigen retrieval. Any nuclear reactivity for estrogen receptor was considered a positive result.
Result: Focal positive nuclear reaction for estrogen receptor was detected in 7 (7.6%) cases of primary pulmonary adenocarcinoma using antibody 1D5, 13 (14.1%) using 6F11, and 25 (27.2%) using SP1. The differences in reactivity for estrogen receptor in pulmonary adenocarcinomas between SP1 and 1D5, and between SP1 and 6F11 were statistically significant (P<0.001). Positive cases showed only a focal pattern of staining with each of the 3 antibodies. There was no significant difference in reactivity for estrogen receptor in pulmonary adenocarcinomas of men and women. Positive staining was highest in nonmucinous bronchioloalveolar adenocarcinomas for all of the antibodies, and for SP1, variation by histologic subtype was significant (P<0.001).
Conclusions: SP1 has a significantly higher detection rate for the expression of estrogen receptor in pulmonary adenocarcinomas when compared with either 1D5 or 6F11. Caution should therefore be exercised in the use of this antibody alone in distinguishing a metastatic breast from a primary pulmonary adenocarcinoma.