Microsatellite instability and clinicopathological features in esophageal squamous cell cancer.
Since multiple genetic alterations are involved in the molecular pathogenesis of esophageal squamous cell cancer (ESCC), the role of microsatellite instability (MSI) in its carcinogenesis is not well defined. The reported frequency of MSI in ESCC ranges from 2 to 66.7% but the majority of the results are derived from relatively small studies. Therefore, we carried out a precise MSI analysis on a large number of ESCC samples to clarify the significance of MSI in the ESCC tumorigenesis. The MSI status of the DNA extracted from 62 ESCC samples and 62 counterpart-normal esophageal epitheliums were studied with five NCI panel markers and ten microsatellite markers located in 17q24-25. Forty-four paraffin-embedded samples and 18 frozen samples from the ESCC patients who underwent surgery were studied. The MSI status was classified as MSS (microsatellite stable), MSI-L (low-level MSI; <30% of markers examined showed instability) and MSI-H (high-level MSI; >30% of markers reported instability). Among the 62 ESCC cases analyzed by the 15 microsatellite markers, 38 out of 62 cases (61.3%) showed MSS, 19 out of 62 cases (30.6%) showed MSI-L and 5 out of 62 cases (8.1%) showed MSI-H. Although the MSI status was not associated with the status of lymph node metastasis or a histological type of cancer, the depth of cancer invasion was significantly associated with the frequency of MSS status and the levels of MSI-L were inversely correlated with the depth of invasion (T1/T2 vs. T3/4; P=0.0007). However, MSI status was not associated with the prognosis of the ESCC patients. This is the first large scale MSI analysis of the ESCC in comparison with the clinicopathological features. Relatively high frequency of MSI-L was observed in ESCC and the frequency of MSI-L was inversely correlated with the depth of invasion.
Matsumoto
Yusuke
Y
Department of Gastroenterological Surgery and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Nagasaka
Takeshi
T
Kambara
Takeshi
T
Hoshizima
Naoko
N
Murakami
Jun
J
Sasamoto
Hiromi
H
Hosokawa
Masao
M
Naomoto
Yoshio
Y
Isozaki
Hiroshi
H
Shimizu
Kenji
K
Tanaka
Noriaki
N
Matsubara
Nagahide
N
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D011379:Prognosis; D015996:Survival Rate