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Invited Critique
November 1, 2006

MKK4 Status Predicts Survival After Resection of Gastric Adenocarcinoma—Invited Critique

Arch Surg. 2006;141(11):1100. doi:10.1001/archsurg.141.11.1100

Cunningham et al have described the results of IHC staining for the MKK4 gene in a group of 124 patients who underwent resection of GA during a 12-year period. The authors have long-term follow-up data for 114 of these patients that represent the basis for the article. They have shown significantly worse survival in patients with MKK4-negative tumors. They believe that MKK4 acts as a tumor suppressor gene and that its mutation results in a more aggressive tumor with a negative effect on survival. MKK4 may prove to be an important predictor of survival in patients with GA, but serious limitations of this study render that conclusion premature. Only 9 of 114 patients had MKK4-negative tumors and form the basis for a broad conclusion backed by complicated statistical analysis on these few tumors. More of the patients with MKK4-positive tumors had more advanced disease (86% vs 63%) and a greater frequency of positive tumor margins (43% vs 29%). However, because of the small number of patients in the MKK4-negative group, these are statistically insignificant values. Because of the nature of the data, more complicated analysis is impossible, as opposed to the analysis provided about the significance of MKK4 on survival. In addition, no data are given about differences in postoperative therapy or operative mortality between the groups, both of which could contribute to long-term survival differences, given the few patients in 1 group. While I congratulate the authors on the publication of an important article about MKK4 and its role in GA, determining its prognostic value in this disease will require larger, multi-institutional studies.

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