title: An analysis of potential surrogate markers of target-specific therapy in archival materials of adrenocortical carcinoma.
abstract: Adrenocortical carcinoma (ACC) is a rare neoplasm but some of the cases are highly malignant. Clinical outcome of the patients with advanced ACC still remained poor or dismal despite recent development of aggressive antitumor therapies. Target-specific therapies have been developed in a number of human malignancies and resulted in therapeutic benefits in some cancer patients. However, these therapies are only effective in the cases in which corresponding targets are expressed in tumor tissues. Therefore, we evaluated expression of potential surrogate markers using immunohistochemistry in archival materials of adrenocortical carcinoma in order to explore the potential application of target specific therapies in ACC in this study. We immunolocalized ten established or potential surrogate markers of target-specific therapies, located in the Ras/extracellular signal-regulated kinase and phosphatidylinositol-3 kinase/Akt pathways, in 41 ACC cases, 54 adrenocortical adenoma (ACA) cases, and five nonpathological adrenal glands and correlated the findings with clinicopathological factors of the patients. Among these markers examined, only epidermal growth factor receptor (EGFR) was significantly more abundant in ACC than in ACA (P < 0.01). These findings suggest that the agents which specifically inhibit signal transductions through EGFR such as monoclonal antibodies against EGFR are considered to be worthwhile to be attempted in future clinical studies.
authors.affiliation: Department of Pathology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Akahira
authors.forename: Ryo
authors.initials: R
authors.lastname: Morimoto
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Satoh
authors.forename: Shigeto
authors.initials: S
authors.lastname: Ishidoya
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D018246:Adrenocortical Adenoma; D018268:Adrenocortical Carcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases