Apoptotic cell death and its relationship to gastric carcinogenesis.
OBJECTIVE
To investigate the apoptotic process of cells within the intestinal metaplasia areas co-localizing with chronic gastritis and gastric carcinomas and to analyze the involvement of proteins regulating apoptosis in the process of intestinal metaplasia related gastric carcinogenesis.


METHODS
Forty-two gastric carcinoma and seventeen chronic gastritis cases were included in this study. All cases were examined for the existence of intestinal metaplasia. Ten cases randomly selected from each group were processed for TUNEL assay. TUNEL positive cells within the intestinal metaplasia areas, co-localizing either to gastric carcinoma or chronic gastritis, were counted and converted to apoptotic indices. In addition, p53, bcl-2 and bax expression patterns within these tissues were analyzed on the basis of immunohistochemistry.


RESULTS
Twenty-eight of the cases were intestinal and 14 of the cases were diffuse type adenocarcinomas. 64% (27/42) of the gastric carcinoma cases had intestinal metaplasia. Intestinal metaplasia co-localized more with intestinal type carcinomas compared with diffuse type carcinomas [75% (21/28) vs 42% (6/14), respectively; P<or=0.05]. The mean apoptotic index in tumor cells was 0.70+/-0.08. The mean apoptotic index in intestinal metaplasias co-localizing to tumors was significantly higher than that of intestinal metaplasias co-localizing to chronic gastritis (0.70+/-0.03 vs 0.09+/-0.01, respectively; P<or=0.05). p53 positivity was not observed in areas of intestinal metaplasia adjacent to tumors or chronic gastritis. Intestinal metaplasia areas adjacent to tumors showed lower cytoplasmic bcl-2 positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [55.5% (15/27) vs 70.5% (12/17), respectively]. On the other hand, intestinal metaplasia areas adjacent to tumors showed significantly higher cytoplasmic bax positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [44.4% (12/27) vs 11.7% (2/17), respectively; P<or=0.05].


CONCLUSIONS
Existence of apoptotic cells on the basis of TUNEL positivity is shown in intestinal metaplasias co-localizing to both diffuse and intestinal type gastric cancers in this study. Our results also suggested bax expression dependent induction of apoptosis especially in intestinal metaplasia areas adjacent to tumors. These findings strongly support the involvement of apoptotic mechanisms in the process of gastric carcinogenesis especially in the transition from intestinal metaplasia to gastric cancer. It may be suggested that induction of apoptosis in intestinal metaplasia areas adjacent to tumors may involve different mechanisms than induction by chronic inflammation.
Bir
Ferda
F
Pamukkale Universitesi Tip Fakultesi, Patoloji ABD, Morfoloji, Kinikli 20070, Denizli, Turkey. fbir@pamukkale.edu.tr
Calli-Demirkan
Nese
N
Tufan
A Cevik
AC
Akbulut
Metin
M
Satiroglu-Tufan
N Lale
NL
D000328:Adult; D000368:Aged; D017209:Apoptosis; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013274:Stomach Neoplasms / Q000737:chemistry / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000032:analysis
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein