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.


OBJECTIVE
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.


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.
Cassaro
Mauro
M
Department of Diagnostic Medicine & Special Therapies, University of Padova, II Pathology Unit, Padova, Italy.
Rugge
Massimo
M
Tieppo
Chiara
C
Giacomelli
Luciano
L
Velo
Daniela
D
Nitti
Donato
D
Farinati
Fabio
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D008297:Male; D008679:Metaplasia / Q000378:metabolism / Q000382:microbiology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D015588:Observer Variation; D011230:Precancerous Conditions / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D019098:Telomerase / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases; D019098:Telomerase; D053148:Caspase 3