Chemosensitivity and survival in gastric cancer patients with microsatellite instability.
BACKGROUND
Conflicting data exist regarding the relevance of high-frequency microsatellite instability (MSI-H) for predicting the prognosis and benefits of 5-fluorouracil (5-FU)-based chemotherapy. This study investigated the usefulness of MSI as either a prognostic indicator or predictor of distinct clinical attributes regarding the use of adjuvant chemotherapy with 5-FU and its analogues in gastric cancer.


METHODS
Data and tumor specimens were collected from 240 gastric cancer patients from 1993 to 2002. Five microsatellite loci were analyzed using a high-intensity microsatellite analysis reported previously. A Cox proportional hazard model was used to compare the clinical data and survival as well as any associations between MSI and 5-FU treatment status of patients with MSI or microsatellite stability (MSS) gastric cancers. A 3-(4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted in 168 cases to investigate chemosensitivity to 5-FU.


RESULTS
This analysis identified 22 MSI-H (9.4%), 25 MSI-L (10.7%), and 193 MSS (79.9%) tumors. Gastric cancer with MSI-H tended to have increased likelihood to show higher age, antral location of the tumor, and lymph vessel involvement (P < 0.05). Univariate analyses failed to show any difference between the MSI-H and MSS/MSI-L groups with respect to overall survival. Furthermore, survival after the administration of 5-FU did not correlate with MSI status, and MSI was not associated with 5-FU sensitivity by MTT assay.


CONCLUSIONS
The results of this study indicate that MSI status has no clear influence on overall survival or response to 5-FU in gastric cancer.
Oki
Eiji
E
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. okieiji@surg2.med.kyushu-u.ac.jp
Kakeji
Yoshihiro
Y
Zhao
Yan
Y
Yoshida
Rintaro
R
Ando
Koji
K
Masuda
Takanobu
T
Ohgaki
Kippei
K
Morita
Masaru
M
Maehara
Yoshihiko
Y
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D015996:Survival Rate
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil