Potential role and chronology of abnormal expression of the Deleted in Colon Cancer (DCC) and the p53 proteins in the development of gastric cancer.
BACKGROUND
Loss of activity of tumor suppressor genes is considered a fundamental step in a genetic model of carcinogenesis. Altered expression of the p53 and the Deleted in Colon Cancer (DCC) proteins has been described in gastric cancer and this event may have a role in the development of the disease. According to this hypothesis, we investigated the p53 and the DCC proteins expression in different stages of gastric carcinomas.


METHODS
An immunohistochemical analysis for detection of p53 and DCC proteins expression was performed in tumor tissue samples of patients with UICC stage I and II gastric cancer. For the purpose of the analysis, the staining results were related to the pathologic data and compared between stage categories.


RESULTS
Ninety-four cases of gastric cancer were analyzed. Disease stage categories were pT1N0 in 23 cases, pT2N0 in 20 cases, pT3N0 in 20 cases and pT1-3 with nodal involvement in 31 cases. Stage pT1-2N0 tumors maintained a positive DCC expression while it was abolished in pT3N0 tumors (p <.001). A significant higher proportion of patients with N2 nodal involvement showed DCC negative tumors. In muscular-invading tumors (pT2-3N0) the majority of cases showed p53 overexpression, whereas a significantly higher proportion of cases confined into the mucosa (pT1N0) showed p53 negative tumors. Also, a higher frequency of p53 overexpression was detected in cases with N1 and N2 metastatic lymph nodal involvement.


CONCLUSIONS
Altered expression of both DCC and p53 proteins is detectable in gastric carcinomas. It seems that loss of wild-type p53 gene function and consequent p53 overexpression may be involved in early stages of tumor progression while DCC abnormalities are a late event.
Graziano
F
F
Medical Oncology Unit, Hospital of Urbino, Italy. frada@tin.it
Cascinu
S
S
Staccioli
M P
MP
Catalano
V
V
Rossi
M C
MC
Baldelli
A M
AM
Giordani
P
P
Muretto
P
P
Catalano
G
G
D000368:Aged; D000369:Aged, 80 and over; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000503:physiopathology; D000075389:DCC Receptor; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016163:Genes, DCC / Q000235:genetics / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology; D011956:Receptors, Cell Surface; D013274:Stomach Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D011956:Receptors, Cell Surface; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins