Fig 1: Histologic expression in patients harboring CTNNB1 and KCNJ5 mutations and in WT patients.(A) H&E stain of investigated adenoma. The WT was from adrenal cortex. (B) CYP11B2 expressed diffusely on adenoma harboring CTNNB1 mutation and mottled expression on adenoma harboring KCNJ5 mutation. (C) However, CYP11B1 stating showed strong expression at there with low CYP11B2 expression. (D) Adenomas displayed weak nuclear and cytoplasmic active ß-catenin expression, especially in female patients harboring CTNNB1 mutation. Bar, 50 mm (X40) and (E) in a high magnification view (X400). (F) LHGHR was diffusely expressed in the adrenal tissue and was also prominent in adenomas harboring CTNNB1 mutation. (G) GnRHR showed diffuse cytoplasmic, membranous and nuclear expression in adenomas, and was most enhanced in adenomas harboring CTNNB1 mutation or wild type. (H) The tissue expression of GATA4 in adrenal tissue was not significant. Abbreviations ABC, active ß–catenin; GnRHR, gonadotropin-releasing hormone receptor, HE, hematoxyline and eosin. LHGHR, luteinizing hormone-chorionic gonadotropin receptor.
Fig 2: Waterfall plot showing absolute change in ER (A), PR (B), AR (C), FSHR (D), LHR (E), and GnRHR (F). Quantitative hormone receptor change was calculated as quantitative expression in the recurrent specimen minus that in the primary specimen in each case. For ER, PR, AR and GnRHR, this change was the difference in positive staining proportion. For FSHR and LHR, the change was IRS difference. Plots on the horizontal line represent unchanged status. Plots over and under the horizontal line represent increased and decreased positive staining proportion or IRS, respectively.
Fig 3: GnRHR expression in EOC cells and the pro-apoptotic effect by different concentrations of goserelin at different time-points. (A) Western blot analysis of GnRHR expression in SKOV3, SKOV3-ip and A2780 cells. Flow cytometric analysis of total apoptosis rate of SKOV3-ip cells after treatment with goserelin for 48 (B) and 72 h (C). *P<0.05, one-way ANOVA was performed for comparisons between goserelin and PBS group.
Fig 4: GnRHa-ICG localizes to GnRHR expression in peritoneal ovarian cancer. Representative images of the (A) peritoneal cavity and (B) mesentery 2 h after the injection of GnRHa-ICG and ICG. Yellow dotted lines indicate the tumor location. (C) Histopathological analysis of a tumor slice showing the colocalization of tumor cells, GnRHR expression, and GnRHa-ICG fluorescence. (D) Comparison of fluorescence intensities between the tumor, muscle, and intestine.
Fig 5: Gonadotropin-releasing hormone receptor is overexpressed in human ovarian cancer. Scatter plot of the GnRHR mRNA expression level in (A) serous ovarian cancer, (B) breast cancer, endometrial cancer, and prostate cancer from the TCGA dataset. (C) Relative GnRHR mRNA expression in human normal tissues. (D) Representative IHC staining for GnRHR in high-grade serous ovarian cancer. (E) Western blot showing GnRHR expression in different cell lines.
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