title: Poorly Differentiated Medullary Phenotype Predicts Poor Survival in Early Lymph Node-Negative Gastro-Esophageal Adenocarcinomas.
abstract: BACKGROUND
  5-year survival rate in patients with early adenocarcinoma of the gastro-esophageal junction or stomach (AGE/S) in Caucasian patients is reported to be 60-80%. We aimed to identify prognostic markers for patients with UICC-I without lymph-node involvement (N0).
  
  
  METHODS
  Clinical data and tissue specimen from patients with AGE/S stage UICC-I-N0, treated by surgery only, were collected retrospectively. Tumor size, lymphatic vessel or vein invasion, grading, classification systems (WHO, Lauren, Ming), expression of BAX, BCL-2, CDX2, Cyclin E, E-cadherin, Ki-67, TP53, TP21, SHH, Survivin, HIF1A, TROP2 and mismatch repair deficiency were analyzed using tissue microarrays and correlated with overall and tumor related survival.
  
  
  RESULTS
  129 patients (48 female) with a mean follow-up of 129.1 months were identified. 5-year overall survival was 83.9%, 5-year tumor related survival was 95.1%. Poorly differentiated medullary cancer subtypes (p<0.001) and positive vein invasion (p<0.001) were identified as risk factors for decreased overall-and tumor related survival. Ki-67 (p = 0.012) and TP53 mutation (p = 0.044) were the only immunohistochemical markers associated with worse overall survival but did not reach significance for decreased tumor related survival.
  
  
  CONCLUSIONS
  In the presented study patients with AGE/S in stage UICC-I-N0 had a better prognosis as previously reported for Caucasian patients. Poorly differentiated medullary subtype was associated with reduced survival and should be considered when studying prognosis in these patients.
authors.affiliation: Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.|Berlin Institute of Health (BIH), Berlin, Germany.
authors.forename: Christoph
authors.identifier: http://orcid.org/0000-0001-9120-6773
authors.initials: C
authors.lastname: Treese
authors.affiliation: Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Pedro
authors.initials: P
authors.lastname: Sanchez
authors.affiliation: Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.|Department of Gastroenterology and Endocrinology, Zentralklinik Bad Berka GmbH, Bad Berka, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Grabowski
authors.affiliation: Institute for Pathology, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Erika
authors.initials: E
authors.lastname: Berg
authors.affiliation: Institute for Pathology, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bläker
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Städtisches Klinikum Solingen GmbH, Solingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kruschewski
authors.affiliation: Department of General, Visceral, Vascular and Thoracic Surgery, Charité University Medicine Berlin, Campus Mitte, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Haase
authors.affiliation: Institute for Pathology, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.affiliation: Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Severin
authors.initials: S
authors.lastname: Daum
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor