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Indefinite for non-invasive neoplasia lesions in gastric intestinal metaplasia: the immunophenotype
  1. Mauro Cassaro1,
  2. Massimo Rugge1,2,
  3. Chiara Tieppo4,
  4. Luciano Giacomelli3,
  5. Daniela Velo4,
  6. Donato Nitti5,
  7. Fabio Farinati
  1. 1Department of Diagnostic Medicine & Special Therapies, University of Padova, II Pathology Unit, Padova, Italy
  2. 2Instituto Oncologico del Veneto, IOV-IRCCS, Pathology Unit, Padova, Italy
  3. 3Azienda Ospedaliera di Padova, Pathology Unit, Padova, Italy
  4. 4Department of Surgical & Gastroenterological Sciences, University of Padova, R Farini Gastroenterology Unit, Padova, Italy
  5. 5Department of Oncological & Surgical Sciences, University of Padova, General Surgery Unit, Padova, Italy
  1. Correspondence to:
 Dr M Rugge
 Cattedra di Anatomia Patologica, Università degli Studi di Padova, Istituto Oncologico del Veneto IOV-IRCCS, Via Aristide Gabelli, 61, 35121 –Padova, Italia; massimo.rugge{at}


Background: In the Padova International Classification, gastric precancerous lesions are labelled as “indefinite for non-invasive neoplasia” (Indef-NiN) cytohistological alterations mimicking non-invasive neoplasia (NiN), but lacking all the attributes required for a definite NiN categorisation.

Aim: To apply a panel of immunohistochemical (IHC) markers of cell proliferation (Mib1), intestinal differentiation (Cdx2), apoptosis (pro-caspase 3) and cell immortalisation (hTERT) to compare the IHC profiles of a series of precancerous lesions arising in gastric intestinalised (ie, IM-positive) glands.

Materials and methods: By applying the histological criteria consistently provided by both the Padova Classification and the World Health Organization International Agency, 112 consecutive cases were considered: intestinal metaplasia (IM; n = 54), Indef-NiN in IM-positive gastric glands (n = 28) and low-grade (LG) NiN (n = 30). In each histological category, the expression of the marker was separately scored in superficial, proliferative and coil compartments.

Results: In all glandular compartments, Mib1, Cdx2, hTERT and pro-caspase 3 were consistently more expressed in LG-NiN than in either IM or Indef-NiN lesions (analysis of variance: p<0.001). Significant ORs (calculated by ordinal logistic regression analysis for each glandular compartment) associated IM, Indef-NiN and LG-NiN with the expression of the considered markers.

Conclusions: A consistent overexpression (unrestricted to the proliferative zone) of IHC markers of cell proliferation, intestinal differentiation, decreased apoptosis and cell immortalisation differentiates LG-NiN from both (simple) IM and Indef-NiN (arising in IM). An increased proliferative activity in the proliferative zone discriminates Indef-NiN lesions (ie, hyperproliferative IM) from IM. Such divergent IHC profiles may provide a rationale for scheduling follow-up protocols more properly tailored on the patient’s risk for cancer.

  • ANOVA, analysis of variance
  • IHC, immunohistochemical
  • IM, intestinal metaplasia
  • Indef-NiN, indefinite for non-invasive neoplasia
  • LG, low grade
  • NiN, non-invasive neoplasia
  • NSAID, non-steroidal anti-inflammatory drug
  • PBS, phosphate-buffered saline

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  • Funding: This study was supported by the Oncology Institute of the Veneto Region (IOV-IRCCS), the Italian Association for Cancer Research (AIRC) and the Farini Association for Gastroenterological Research.

  • Competing interests: None declared.