Microsatellite instability in gastric cancer is associated with better prognosis in only stage II cancers

被引:146
作者
Beghelli, S
de Manzoni, G
Barbi, S
Tomezzoli, A
Roviello, F
Di Gregorio, C
Vindigni, C
Bortesi, L
Parisi, A
Saragoni, L
Scarpa, A
Moore, PS
机构
[1] Univ Verona, Dipartimento Patol, I-37134 Verona, Italy
[2] Univ Verona, Sect Anat Pathol, I-37134 Verona, Italy
[3] Univ Verona, Surg Div 1, Borgo Trento Hosp, I-37134 Verona, Italy
[4] Borgo Trento Hos, Div Pathol, I-37134 Verona, Italy
[5] Univ Siena, Hosp Le Scotte, Div Surg Oncol, I-53100 Siena, Italy
[6] Carpi Hosp, Sect Anat Pathol, I-53100 Siena, Italy
[7] Univ Siena, Div Pathol, Dept Pathol & Oncol, I-53100 Siena, Italy
[8] Pierantoni Morgagni Hosp, Div Pathol, Forlz, Italy
关键词
D O I
10.1016/j.surg.2005.08.021
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. The assessment of microsatellite instability (MSI) is not included yet in the routine evaluation of patients with gastric cancer, as controversial data exist regarding its prognostic value. Methods. We determined the clinical significance of MSI in 510 sporadic gastric cancers, using the mononucleotide markers BAT25 and BAT26. The results were compared with the immunohistochemical expression, of the mismatch repair proteins Mlh1 and Msh2. Results. MSI was present in 83 (16%) cancers and correlated with better survival (P < .001). Multivariate analysis showed that the MSI phenotype was an independent factor (P = .005) and added prognostic information to TNM stage, location, and age. The relative risk of death for MSI cancer patients was 0.6 (95% confidence interval [CI], 0.4-0.8). Moreover, when grouped according to stage, only stage II cancers showed a significant effect of MSI status on survival (P = .011; hazard ratio = 0.3; 95% CI, 0.1-0.8). MSI also correlated with older age (P = .002), female gender (P < .001), intestinal histotype (P = .011), lower T stage (P = .018), and less lymph node involvement (P < .001). Finally, comparison of the results of immunohistochemical expression of the mismatch repair proteins Mlh1 and Msh2 with microsatellite analysis showed concordant results in 95% of neoplasms, with a sensitivity of 82% and specificity of 98%. Conclusions. Microsatellite analysis of gastric cancer has clinical utility in determination of prognosis, but should be determined in only stage H neoplasms in a routine clinical setting. Immunohistochemistry may be considered sufficient, although microsatellite analysis is preferable.
引用
收藏
页码:347 / 356
页数:10
相关论文
共 44 条
[11]   Allelic imbalance of 8p indicates poor survival in gastric cancer [J].
French, AJ ;
Petroni, G ;
Thibideau, SN ;
Smolkin, M ;
Bissonette, E ;
Roviello, F ;
Harper, JC ;
Koch, BR ;
Anderson, SA ;
Hebbring, SJ ;
Powell, SM .
JOURNAL OF MOLECULAR DIAGNOSTICS, 2004, 6 (03) :243-252
[12]   Origin of microsatellite instability in gastric cancer [J].
Halling, KC ;
Harper, J ;
Moskaluk, CA ;
Thibodeau, SN ;
Petroni, GR ;
Yustein, AS ;
Tosi, P ;
Minacci, C ;
Roviello, F ;
Piva, P ;
Hamilton, SR ;
Jackson, CE ;
Powell, SM .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (01) :205-211
[13]   The role of microsatellite instability in gastric carcinoma [J].
Hayden, JD ;
Martin, IG ;
Cawkwell, L ;
Quirke, P .
GUT, 1998, 42 (02) :300-303
[14]  
Hermanek P, 1992, CLASSIFICATION MALIG
[15]   Preoperative genetic diagnosis of gastric carcinoma based on chromosomal loss and Microsatellite instability [J].
Hong, SJ ;
Choi, SW ;
Lee, KH ;
Lee, S ;
Min, KO ;
Rhyu, MG .
INTERNATIONAL JOURNAL OF CANCER, 2005, 113 (02) :249-258
[16]   Cancer statistics, 2002 [J].
Jemal, A ;
Thomas, A ;
Murray, T ;
Thun, M .
CA-A CANCER JOURNAL FOR CLINICIANS, 2002, 52 (01) :23-47
[17]   Frequency of loss of hMLH1 expression in colorectal carcinoma increases with advancing age [J].
Kakar, S ;
Burgart, LJ ;
Thibodeau, SN ;
Rabe, KG ;
Petersen, GM ;
Goldberg, RM ;
Lindor, NM .
CANCER, 2003, 97 (06) :1421-1427
[18]  
KELLER G, 1995, AM J PATHOL, V147, P593
[19]  
Keller G, 1998, AM J PATHOL, V152, P1281
[20]   Surgical approaches and outcomes in the treatment of gastric cancer [J].
Kim, HJ ;
Karpeh, MS .
SEMINARS IN RADIATION ONCOLOGY, 2002, 12 (02) :162-169