MKK4 status predicts survival after resection of gastric adenocarcinoma.
OBJECTIVE
Lack of expression of the tumor-suppressor gene MKK4 is significantly correlated with poor survival after resection of gastric adenocarcinoma.


METHODS
Retrospective review of medical records after construction and immunolabeling of tissue microarrays for clinical correlation.


METHODS
The Johns Hopkins Hospital, Baltimore, Md.


METHODS
Patients operated on because of gastric adenocarcinoma between 1983 and 1995. Main Outcome Measure Long-term survival and MKK4 status.


RESULTS
Primary tumors (N = 124) were scored as 0 (no labeling), 1+ (weak labeling), or 2+ (strong labeling) in 9 (7%), 80 (65%), and 35 (28%) patients, and 5-year survival in these patients was 0%, 21%, and 28%, respectively. Given the small size (7%) of the MKK4-negative group (as expected, given the 5%-10% incidence of genetic loss in carcinomas), a Cox proportional hazards analysis was performed, adjusting for age, sex, and tumor stage. This multivariate analysis revealed a 5-fold increased risk of death (P<.001) in patients whose primary tumors were MKK4-negative. Furthermore, the addition of MKK4 status significantly improved the Cox model, changing log likelihood from -1410 to -369, confirming that MKK4 status was truly the effector of the survival difference and not a bystander.


CONCLUSIONS
The lack of expression of the tumor-suppressor gene MKK4 in resected gastric adenocarcinoma is robustly associated with poor survival. This finding may provide a useful prognostic tool in patients with gastric adenocarcinoma.
Cunningham
Steven C
SC
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231-1000, USA.
Kamangar
Farin
F
Kim
Min P
MP
Hammoud
Sommer
S
Haque
Raqeeb
R
Iacobuzio-Donahue
Christine
C
Ashfaq
Raheela
R
Kern
Scott E
SE
Maitra
Anirban
A
Heitmiller
Richard E
RE
Choti
Michael A
MA
Lillemoe
Keith D
KD
Cameron
John L
JL
Yeo
Charles J
CJ
Montgomery
Elizabeth
E
Schulick
Richard D
RD
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D000368:Aged; D016009:Chi-Square Distribution; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D048670:MAP Kinase Kinase 4 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D015996:Survival Rate
D048670:MAP Kinase Kinase 4