title: The Proportion of Signet Ring Cell Component in Patients with Localized Gastric Adenocarcinoma Correlates with the Degree of Response to Pre-Operative Chemoradiation.
abstract: BACKGROUND
  Patients with localized gastric adenocarcinoma (LGAC), who get pre-operative therapy, have heterogeneous/unpredictable outcomes. Predictive clinical variables/biomarkers are not established.
  
  
  METHODS
  We analyzed 107 LGAC patients who had chemoradiation and surgery. LGACs were grouped for (1) presence/absence of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC was assessed (0, 1-10, 11-49, and 50-100%) and correlated with pathologic complete response (pathCR) or <pathCR in the resected specimens.
  
  
  RESULTS
  Most patients were men (60%), had stage cIII LGAC (50%), and received chemotherapy before chemoradiation (93%). Most had G3 tumors (78%) and SRC (58%). Presence of SRC was associated with a lower rate of pathCR (11 vs. 36%, p = 0.004), and the association remained significant even with a low percentage of SRC (1-10%; p = 0.014). The higher the fraction of SRC, the lower was the probability of pathCR (p = 0.03). G3 and SRC led to a shorter overall survival (OS) (p = 0.046 and p = 0.038, respectively). yp stage independently prognosticated OS and recurrence-free survival (p < 0.001).
  
  
  CONCLUSIONS
  Our novel findings suggest that LGACs with SRC are relatively chemoradiation resistant compared to LGACs without SRC. A higher fraction of SRC is associated with higher resistance. Upon validation/biomarker(s) evaluation, reporting of the fraction of SRC may be warranted.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Tex., USA.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Charalampakis
authors.forename: Graciela M
authors.initials: GM
authors.lastname: Nogueras González
authors.forename: Elena
authors.initials: E
authors.lastname: Elimova
authors.forename: Roopma
authors.initials: R
authors.lastname: Wadhwa
authors.forename: Hironori
authors.initials: H
authors.lastname: Shiozaki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shimodaira
authors.forename: Mariela A
authors.initials: MA
authors.lastname: Blum
authors.forename: Jane E
authors.initials: JE
authors.lastname: Rogers
authors.forename: Kazuto
authors.initials: K
authors.lastname: Harada
authors.forename: Aurelio
authors.initials: A
authors.lastname: Matamoros
authors.forename: Tara
authors.initials: T
authors.lastname: Sagebiel
authors.forename: Prajnan
authors.initials: P
authors.lastname: Das
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Minsky
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lee
authors.forename: Brian
authors.initials: B
authors.lastname: Weston
authors.forename: Manoop S
authors.initials: MS
authors.lastname: Bhutani
authors.forename: Jeannelyn S
authors.initials: JS
authors.lastname: Estrella
authors.forename: Brian D
authors.initials: BD
authors.lastname: Badgwell
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018279:Carcinoma, Signet Ring Cell / Q000628:therapy*; D059248:Chemoradiotherapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D057234:Preoperative Period; D011379:Prognosis; D013274:Stomach Neoplasms / Q000473:pathology* / Q000628:therapy*; D016896:Treatment Outcome