Lynn Schoenfield1, Sarah Janse2, David Kline2, Mary E Aronow3, Arun D Singh4, Caroline Craven5, Mohamed Abdel-Rahman5, Colleen M Cebulla5. 1. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. 2. Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. 3. Retina Service and Ocular Melanoma Center, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. 4. Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. 5. Department of Ophthalmology and Visual Sciences, Havener Eye Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Abstract
BACKGROUND: Metastatic uveal melanoma (UM) has no effective treatment. To date, no publications have reported immunohistochemical evidence of estrogen receptors (ERs) in UM; however, changes in pathologic reporting for ER in breast carcinoma prompted a re-examination of ER in UM, as it could represent a potential therapeutic target. OBJECTIVE: To determine if UM tumors express ER by immunohistochemistry (IHC) using current methodology for breast cancer and to evaluate ER gene expression using a publicly available UM database. METHODS: A retrospective IHC analysis with clinical correlation was performed on 2 cohorts: 57 cases from the Cleveland Clinic (CC) and 50 from the Ohio State University Wexner Medical Center (OSUWMC). Analysis of The Cancer Genome Atlas Project (TCGA) UM Dataset of 80 patients was also performed. RESULTS: Presence of ER was detected by IHC in 20 of 34 (59%) analyzable cases in the CC cohort. Of the 50 patients in the OSU cohort, 52 specimens from 47 patients were sufficient for analysis. Of these 47 cases, 29 (62%) had tumor that was ER positive in ≥1% nuclei. In the second cohort, positivity was classified as positive (≥10% nuclei, 34% cases) or low positive (1-9% nuclei, 28% cases). In 5 patients, there were paired samples, that is, primary tumor and subsequent recurrence or metastasis, with concordance for ER in 4 of 5 cases. In the TCGA database, elevated ESR1 and ESR2 gene expression was identified in a subset of UM tumors with poor genetic prognostic features. CONCLUSIONS AND RELEVANCE: Potentially actionable ER expression is present in greater than half of UM cases by IHC. Gene expression of ESR1 and ESR2 was elevated in a subset of UM tumors with poor prognostic features. These data provide a rationale to evaluate ER as a potential target for therapy in UM.
BACKGROUND: Metastatic uveal melanoma (UM) has no effective treatment. To date, no publications have reported immunohistochemical evidence of estrogen receptors (ERs) in UM; however, changes in pathologic reporting for ER in breast carcinoma prompted a re-examination of ER in UM, as it could represent a potential therapeutic target. OBJECTIVE: To determine if UM tumors express ER by immunohistochemistry (IHC) using current methodology for breast cancer and to evaluate ER gene expression using a publicly available UM database. METHODS: A retrospective IHC analysis with clinical correlation was performed on 2 cohorts: 57 cases from the Cleveland Clinic (CC) and 50 from the Ohio State University Wexner Medical Center (OSUWMC). Analysis of The Cancer Genome Atlas Project (TCGA) UM Dataset of 80 patients was also performed. RESULTS: Presence of ER was detected by IHC in 20 of 34 (59%) analyzable cases in the CC cohort. Of the 50 patients in the OSU cohort, 52 specimens from 47 patients were sufficient for analysis. Of these 47 cases, 29 (62%) had tumor that was ER positive in ≥1% nuclei. In the second cohort, positivity was classified as positive (≥10% nuclei, 34% cases) or low positive (1-9% nuclei, 28% cases). In 5 patients, there were paired samples, that is, primary tumor and subsequent recurrence or metastasis, with concordance for ER in 4 of 5 cases. In the TCGA database, elevated ESR1 and ESR2 gene expression was identified in a subset of UM tumors with poor genetic prognostic features. CONCLUSIONS AND RELEVANCE: Potentially actionable ER expression is present in greater than half of UM cases by IHC. Gene expression of ESR1 and ESR2 was elevated in a subset of UM tumors with poor prognostic features. These data provide a rationale to evaluate ER as a potential target for therapy in UM.
Authors: S Mallone; E De Vries; M Guzzo; E Midena; J Verne; J W Coebergh; R Marcos-Gragera; E Ardanaz; R Martinez; M D Chirlaque; C Navarro; G Virgili Journal: Eur J Cancer Date: 2011-11-25 Impact factor: 9.162
Authors: M Elizabeth H Hammond; Daniel F Hayes; Mitch Dowsett; D Craig Allred; Karen L Hagerty; Sunil Badve; Patrick L Fitzgibbons; Glenn Francis; Neil S Goldstein; Malcolm Hayes; David G Hicks; Susan Lester; Richard Love; Pamela B Mangu; Lisa McShane; Keith Miller; C Kent Osborne; Soonmyung Paik; Jane Perlmutter; Anthony Rhodes; Hironobu Sasano; Jared N Schwartz; Fred C G Sweep; Sheila Taube; Emina Emilia Torlakovic; Paul Valenstein; Giuseppe Viale; Daniel Visscher; Thomas Wheeler; R Bruce Williams; James L Wittliff; Antonio C Wolff Journal: Arch Pathol Lab Med Date: 2010-07 Impact factor: 5.534