title: The zinc-finger transcription factor SALL4 is frequently expressed in human cancers: association with clinical outcome in squamous cell carcinoma but not in adenocarcinoma of the esophagus.
abstract: SALL4 is a transcription factor originally identified as a homeotic gene essential for organ development. Early studies suggested that SALL4 is a useful marker to identify testicular and ovarian germ cell tumors. The aim of the study was to evaluate the diagnostic potential of SALL4 immunohistochemistry. Immunohistochemical staining was performed on a tissue microarray (TMA) with 3966 samples from 94 different tumor types and on a further TMA with 492 esophagus carcinomas. SALL4 immunostaining was by far most prevalent and most intensive in testicular tumors with a positivity rate of 93.1% in seminomas, 80% in mixed germ cell tumors (embryonic carcinomas/yolk sac tumors), and 18.5% in teratomas, respectively. However, SALL4 expression is not specific to germ cell tumors. We observed SALL4 positivity in non-germ cell tumors as carcinomas of the kidney (28.9% of chromophobe, 34.4% of clear cell carcinoma), in intestinal type adenocarcinoma of the stomach (10.9%), in adenocarcinoma (10.5%) and squamous cell carcinoma (7.2%) of the esophagus, and in malignant melanoma (8.1%) and invasive urothelial bladder carcinoma (20%). SALL4 expression was not found in lymphomas, in soft tissue tumors or breast tumors. At analysis of esophagus carcinoma TMA, no significant association was seen between SALL4 expression and overall survival in adenocarcinoma. However, SALL4 expression was strongly associated with worse overall survival in squamous cell carcinoma. SALL4 expression can be found at relevant frequencies in various tumors of different primary sites. SALL4 expression in squamous cell carcinoma of the esophagus may constitute a sign of dedifferentiation leading to poor patient prognosis.
authors.affiliation: Institute for Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. ergin.kilic@charite.de.|Institute for Pathology, University Hospital Charité Berlin, Charitéplatz 1, 10117, Berlin, Germany. ergin.kilic@charite.de.
authors.forename: Ergin
authors.initials: E
authors.lastname: Kilic
authors.affiliation: Institute for Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Pierre
authors.initials: P
authors.lastname: Tennstedt
authors.affiliation: Institute for Vegetative Physiology, University Hospital Charité Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Anica
authors.initials: A
authors.lastname: Högner
authors.affiliation: Institute for Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lebok
authors.affiliation: Institute for Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumonology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.affiliation: Department of Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.affiliation: Institute for Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D009369:Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C472575:SALL4 protein, human; D014157:Transcription Factors
keywords: Adenocarcinoma; Immunohistochemistry; Prognosis in esophagus carcinoma; SALL4; Squamous cell; Tissue micro array
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