Indefinite for non-invasive neoplasia lesions in gastric intestinal metaplasia: the immunophenotype

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.