Overexpression of p73 as a tissue marker for high-risk gastritis.
OBJECTIVE
Histologic assessment of high-risk gastritis for the development of gastric cancer is not well defined. The identification of tissue markers together with the integration of histologic features will be required for this assessment.


METHODS
Matched tumor/nontumor adjacent mucosa (NTAM) of 91 early gastric cancer and 148 chronic gastritis cases were evaluated for histologic characteristics (atrophy, intestinal metaplasia, chronic inflammation, polymorphonuclear infiltration, and Helicobacter pylori) by the Sydney System. Atrophy risk assessment was also evaluated by the Operative Link on Gastritis Assessment (OLGA) staging system. Eight tissue markers (BRCA1, HSP90, STAT1, FHIT, EGFR, p73, p53, p16INK4a) and EBV were also evaluated by tissue microarray/immunohistochemistry/in situ hybridization platform. Data were analyzed by contingency tables (2 x 2) using Fisher's exact two-tailed test (P < 0.001) and integrated by Significance Analysis of Microarrays (SAM) and clustering analysis.


RESULTS
Histologically, NTAM have severe intestinal metaplasia/chronic inflammation and severe atrophy assessed by Sydney and OLGA staging systems. H. pylori infection was similar in both groups, and EBV was found only in 5.5% of the tumor samples. Overexpression of p73 was higher in NTAM (50.5%) than in chronic gastritis (10.8%; P < 0.0001). Integration of histologic features and tissue markers showed that overexpression of p73, severe atrophy, and OLGA stage 4 were the most relevant features in NTAM. Clustering analysis correctly assigned NTAM and control cases (P < 0.0001).


CONCLUSIONS
Overexpression of p73 should be considered for the assessment of high-risk chronic gastritis. SAM allows the integration of histology and tissue markers for this assessment.
Department of Anatomic Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile.
Gonzalo
G
Carrasco
Jose
J
Diaz
Jose R
JR
Valbuena
Paulina
P
Ibanez
Paz
P
Rodriguez
Gabriela
G
Araya
Carolina
C
Rodriguez
Javiera
J
Torres
Ignacio
I
Duarte
Edmundo
E
Aravena
Fernando
F
Mena
Carlos
C
Barrientos
Alejandro H
AH
Corvalan
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D015415:Biomarkers / Q000032:analysis*; D002908:Chronic Disease; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D005756:Gastritis / Q000378:metabolism* / Q000473:pathology*; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008679:Metaplasia / Q000473:pathology; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D011230:Precancerous Conditions / Q000473:pathology; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000473:pathology; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000032:analysis*
D015415:Biomarkers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins