The prognostic impact of tumor cell expression of estrogen receptor‐α, progesterone receptor, and androgen receptor in patients irradiated for nonsmall cell lung cancer

Abstract

BACKGROUND:The current study was performed to investigate the potential impact of tumor cell expression of estrogen receptor-a (ER-a), progesterone receptor (PR), and androgen receptor (AR) on the outcomes of patients who received radiotherapy (RT) for nonsmall cell lung cancer (NSCLC). METHODS: Tumor cell expression of ER-a, PR, and AR as well as 9 additional potential prognostic factors were retrospectively evaluated in 64 patients who underwent RT for AJCC stage II/III NSCLC. The endpoints investigated were locoregional control, metastases-free survival, and overall survival. The additional potential prognostic factors were age, gender, Karnofsky performance score, histology, T classification, N classification, surgery, smoking during RT, and hemoglobin levels during RT. Subgroup analyses were performed for women and men. RESULTS: On univariate analysis, locoregional control was not found to be associated with expression of PR or AR. ER-a expression demonstrated a strong trend toward worse locoregional control. On multivariate analysis, ER-a expression was found to be significantly associated with worse locoregional control (risk ratio [RR], 3.12; P ¼ .035). On univariate analysis, metastases-free survival was not associated with expression of ER-a, PR, or AR. On univariate analysis, survival was found to be negatively associated with expression of ER-a (P ¼ .003) but not with PR or AR expression. On multivariate analysis, ER-a expression maintained significance (RR, 2.73; P ¼ .022). CONCLUSIONS: Tumor cell expression of ER-a was found to be a negative prognostic factor for treatment outcomes in both women and men. Expression of PR and AR was not associated with outcomes.

Estrogen receptors as the novel therapeutic biomarker in non-small cell lung cancer

“…Cytoplasmic and plasma membrane ER-α is mainly detected using clone HC-20 antibody, the epitope for which is in the C-terminus. The detection rate with this antibody is 70%-80%, much higher than with clone 1D5 [5][6][7][8][9][10][11][12][13][14]16,17,[19][20][21][22][23][24][25] ; indeed, we confirmed that ER-α detected using clone HC-20 is nearly always missed by clone 1D5. This suggests that ER-α detected by clone HC-20 may have an N-terminal deletion mutation that prevents its translocation to the nucleus [9,31] .…”

“…Kawai et al [9] α IHC Cytoplasm Worse β IHC Nucleus Better Wu et al [11] β IHC Nucleus Better Schwartz et al [10] β IHC Nucleus Better (male) Skov et al [14] β IHC Nucleus Better (male) Nose et al [16] α IHC Cytoplasm Worse Abe et al [18] β IHC Nucleus Better Mauro et al [20] β IHC Nucleus Better Olivo-Marston et al [30] α RT-PCR NS Worse Stabile et al [21] β IHC Cytoplasm Worse Rouquette et al [25] α IHC Nucleus Better Rades et al [23] α IHC NS Worse Karlsson et al [28] β IHC Nucleus Better (ADCA) Liu et al [29] β2,5 IHC Cytoplasm Better ER: Estrogen receptors; NS: Indicates not specified; ADCA: Adenocarcinoma; IHC: Immunohistochemistry; RT-PCR: Reverse transcription polymerase chain reaction.…”

“…Nuclear ER-α has also been detected using clone 6F11 antibody, which was raised against the full-length form of the receptor molecule [7,8,15,[17][18][19][20]25] . On the other hand, the rate of ER-α detection in NSCLC using clone 1D5 is very low, from 0%-7% [5][6][7][8]10,17,19,23,25] . Moreover, ER-α is reportedly located not only in the nucleus, but also in the cytoplasm and in the plasma membrane [9,[11][12][13][14]16,17,[20][21][22]24] .…”

“…Nucleus/cytoplasm 39%/54% Sun et al [22] HC-20 Cytoplasm 36% Rades et al [23] 1D5 NS 19% Shimizu et al [24] HC-20 Cytoplasm 47% Rouquette et al [25] 1D5 Nucleus 9% F10 Nucleus 8% NS: Indicates not specified.…”

Estrogen receptor alpha promotes smoking-carcinogen-induced lung carcinogenesis via cytochrome P450 1B1

“…Clinically, the over-expression of ERα in non-small-cell lung cancer (NCLSC) patients is predictive of poor outcome in both men and women [9][10][11][12]. ERα expression can also be an independent prognostic factor in metastatic NSCLC [13].…”