Evaluation of malignancy using Ki-67, p53, EGFR and COX-2 expressions in gastrointestinal stromal tumors.
OBJECTIVE
To investigate the role of expressions of Ki-67, p53, epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in gastrointestinal stromal tumor (GIST) grading and prognosis.


METHODS
Tumor tissue was collected retrospectively from 96 patients with GIST. Antibodies against Ki-67, p53, EGFR and COX-2 were used for immunohistochemical staining. Tumor grading was designated according to a consensus system and the staining was quantified in 3 categories for each antibody in the statistical analysis.


RESULTS
The Ki-67 expression in GISTs was significantly associated with the size of the tumors, mitotic rate and the risk of malignancy (χ(2) = 15.51, P = 0.02; χ(2) = 22.27, P < 0.001; χ(2) = 20.05; P < 0.001). The p53 expression was also significantly correlated with mitotic rate and the risk of malignancy (χ(2) = 9.92, P = 0.04; χ(2) = 9.97; P = 0.04). Over-expression of Ki-67 was strongly correlated with poor survival (χ(2) = 10.44, P = 0.006), but no correlation was found between the expression of p53, EGFR or COX-2 and survival. Multivariate analysis further demonstrated that Ki-67 expression (relative risk = 15.78, 95% CI: 4.25-59.37) could be used as an independent prognostic value for GIST patients. Adjuvant imatinib therapy could improve clinical outcomes in the patients with high risk and intermediate risk of recurrence after complete tumor resections (median survival time: 52 mo vs 37 mo, χ(2) = 7.618, P = 0.006).


CONCLUSIONS
Our results indicated that the expression of Ki-67 could be used as an independent prognostic factor for GIST patients.
Division of Clinical Epidemiology, Jilin University First Hospital, Changchun 130021, Jilin Province, China.
Jing
J
Jiang
Mei-Shan
MS
Jin
Jian
J
Suo
Yin-Ping
YP
Wang
Liang
L
He
Xue-Yuan
XY
Cao
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D060787:Neoplasm Grading; D010879:Piperazines / Q000627:therapeutic use; D011379:Prognosis; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D010879:Piperazines; D011743:Pyrimidines; D016159:Tumor Suppressor Protein p53; D000068877:Imatinib Mesylate; D051546:Cyclooxygenase 2; D066246:ErbB Receptors