title: Maspin-related Orchestration of Aggressiveness of Gastric Cancer.
abstract: Although some hypotheses have been postulated on the genesis of gastric cancer (GC), the origin of this disease remains unclear. The aim of this study was to develop a hypothesis about gastric carcinogenesis based on our experience in the field of GC and on published reports on about 28 studies in the field of subcellular maspin expression in GC. In 180 cases of GC, the clinicopathologic features were correlated with the results obtained after paired immunohistochemical stains (tumor/normal mucosa) with 15 antibodies: E-cadherin, HER-2, VEGF, CD31, CD105, COX-2, maspin, bax, bcl-2, p53, Ki67, MLH-1, MSH-2, Mena protein, and vimentin.
  
  
  
  Cytoplasmic maspin was observed in foveolar cells with intestinal metaplasia, whereas mixed (combined nuclear-cytoplasmic) expressions were more characteristic of the intramucosal foci of signet-ring cells and dysplastic cells. The tumor cells that expressed cytoplasmic maspin were mostly intestinal type bax/COX-2/Mena/E-cadherin-positive differentiated adenocarcinomas with nodular growth and more superficial invasion. The nuclear shift of maspin was more frequent in HER-2/p53-positive intestinal type adenocarcinomas with diffuse architecture at the invasion front, as well as for node-positive poorly cohesive carcinomas. Loss of maspin expression induced a higher risk of distant metastases, without differences in the survival rate.
  
  
  
  In GC with associated metaplasia, cytoplasmic maspin is predominant; the nuclear shift induces local aggressiveness and risk of node metastases, whereas total loss can indicate a risk of distant metastases. In GC without associated metaplasia, nuclear expression of maspin is retained, indicating a more aggressive behavior.
authors.affiliation: Departments of *Pathology †Oncology ∥Surgery ¶Intensive Care Unit, University of Medicine and Pharmacy, Tirgu-Mures, Romania ‡Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan §Department of Pathology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.
authors.forename: Simona
authors.initials: S
authors.lastname: Gurzu
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kadar
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.forename: Janina
authors.initials: J
authors.lastname: Orlowska
authors.forename: Tivadar
authors.initials: T
authors.lastname: Bara
authors.forename: Tivadar
authors.initials: T
authors.lastname: Bara
authors.forename: Janos
authors.initials: J
authors.lastname: Szederjesi
authors.forename: Ioan
authors.initials: I
authors.lastname: Jung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005753:Gastric Mucosa / Q000033:anatomy & histology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D015843:Serpins / Q000235:genetics / Q000502:physiology*; D013274:Stomach Neoplasms / Q000473:pathology*; D015996:Survival Rate; D055815:Young Adult
chemical_list: C085344:SERPIN-B5; D015843:Serpins