Different estrogen receptor β expression in distinct histologic subtypes of lung adenocarcinoma

SummaryAdenocarcinoma is becoming the most common histologic type of lung cancer in both sex. Although most cases are seen in smokers, it develops more frequently than other histologic types in individuals who have never smoked. This evidence suggests that other putative etiologic factors, such as sex hormones, need to be investigated. Several subtypes of lung adenocarcinoma have been recently described with distinct clinicopathologic features and prognostic implications. The purpose of this study is to investigate the role of estrogen receptor β in lung adenocarcinoma, with particular attention paid to its different histologic subtypes. Nuclear estrogen receptor β expression was evaluated by immunohistochemistry in 112 lung adenocarcinomas, including both “single subtype” and “mixed subtype” samples. Using a 2-level (high/low) score system, estrogen receptor β expression was high in most (75%) adenocarcinomas and turned out to be strongly related to the histologic subtypes. In fact, estrogen receptor β expression was low or negative in 68.2% of solid subtypes, whereas it was high in 76.5% of nonmucinous bronchioloalveolar, in 69.4% of acinar, and in 61.2% of papillary patterns (P = .00004). Furthermore, a strong association between estrogen receptor β expression and tumor histologic grade was observed: estrogen receptor β was highly expressed predominantly in well- and moderately differentiated tumors (P = .0014). In conclusion, estrogen receptor β expression has distinct patterns in lung adenocarcinoma, suggesting a specific role for estrogen receptor β in the pathogenesis of different histologic subtypes of this type of cancer. Moreover, loss of estrogen receptor β expression in poorly differentiated (G3) tumors could represent a crucial step in the dedifferentiation process of lung adenocarcinoma.