title: Amplifications of EGFR gene and protein expression of EGFR, Her-2/neu, c-kit, and androgen receptor in phyllodes tumor of the prostate.
abstract: Phyllodes tumor of the prostate is a rare neoplasm with an unpredictable clinical behavior. It may undergo early recurrence with sarcomatous transformation or may even metastasize. Because targeted therapies have shown great success against several malignancies, there is hope that these same therapies may show similar promise in the treatment of other neoplasms. This study was undertaken to investigate both amplification of the epidermal growth factor receptor (EGFR) gene by fluorescence in situ hybridization and the overexpression of EGFR, Her-2/neu, CD117 (c-kit), and androgen receptor by immunohistochemical staining in a series of 11 phyllodes tumors of the prostate. In the stromal elements, EGFR gene amplification was present in four of 11 tumors and polysomy chromosome 7 was present in two of 11 tumors. No amplification was present in the epithelial components. Only one of 11 tumors had polysomy of chromosome 7 in the epithelial components. Immunohistochemically, in the stromal components, EGFR expression was demonstrable in four of 11 tumors and androgen receptor was demonstrated in six of 10 tumors. Neither Her-2/neu nor c-kit expression was seen in the stromal components of any of the 11 tumors. In the epithelial components, EGFR expression was present in all 11 tumors with strong staining in the basal cell layers and weak or no staining in luminal epithelium; androgen receptor expression was seen in seven of 10 tumors; Her-2/neu was weakly positive in four of 11 tumors; and c-kit expression was present focally and weakly in two of 11 cases with only 2-5% of cells staining. The highest staining intensity and the highest percentage of positively staining cells were seen with EGFR immunostaining in both the stromal and epithelial (mainly basal cells) components. Androgen receptor staining showed the next highest staining intensity and percentage of positive cells in both components. Her-2/neu and c-kit were only weakly or infrequently expressed in the epithelial components of prostatic phyllodes tumors. Our data indicate that EGFR and androgen receptor are frequently and strongly expressed in both epithelial and stromal components of prostatic phyllodes tumors. EGFR gene amplification is frequently present in prostatic phyllodes tumors and may account for one of the mechanisms leading to protein overexpression in some but not all cases. Anti-EGFR and/or antiandrogen agents may be potentially useful for management of patients with tumors expressing EGFR and/or androgen receptor.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Jones
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.forename: John N
authors.initials: JN
authors.lastname: Eble
authors.forename: David G
authors.initials: DG
authors.lastname: Bostwick
authors.forename: Junqi
authors.initials: J
authors.lastname: Qian
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: John J
authors.initials: JJ
authors.lastname: Harris
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D003557:Phyllodes Tumor / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen