The correlation of microsatellite instability and tumor-infiltrating lymphocytes in hereditary non-polyposis colorectal cancer (HNPCC) and sporadic colorectal cancers: the significance of different types of lymphocyte infiltration.
BACKGROUND
Tumor-infiltrating lymphocytes (TIL) are strictly divided into two categories: those lymphocytes in stroma and those in between cancer cells. However, there has been no fully adequate comparison of these two categories, especially analysis in relation to microsatellite instability (MSI).


METHODS
The materials were derived from patients with colorectal cancer who underwent surgery in Jichi Medical School and Omiya Medical Center. There were 19 hereditary non-polyposis colorectal cancer (HNPCC) patients who were compatible with Japanese criteria A and 106 patients with sporadic colorectal cancer (sCRC) in either Dukes B or C stage. As microsatellite markers, the global standard five markers were selected. Immunohistochemical analysis was performed using the anti-CD3, -CD4, -CD8 and -S-100 antibodies and the results were evaluated according to the degree of infiltration, which was classified into three grades.


RESULTS
As for stroma-infiltrating lymphocytes (SIL) in sCRCs, severe infiltration was observed in 20% of high microsatellite instability (MSI-H) patients and 12.8% of low microsatellite instability (MSI-L)/stable microsatellite (MSS) patients without a statistically significant difference. In contrast, severe infiltration of intra-tumor cell-infiltrating lymphocytes (ITCIL) was observed in 41.7% of MSI-H sCRC patients and 4.3% of MSI-L/MSS patients. Thus, there was a close correlation between ITCIL severity and increased microsatellite instability (P < 0.001). In examination of ITCIL, patients with severe infiltration tended to show a better survival rate than those with moderate or mild infiltration.


CONCLUSIONS
The present study suggests that different factors are involved in the infiltration of SIL and ITCIL. Although there were no statistically significant differences, the cumulative survival rates tended to be higher in severe ITCIL cases than in those with moderate and poor ITCIL (P < 0.09). We suggest that there might be a possibility of ITCIL having a role for a better prognosis after colorectal cancer surgery, which is closely related to MSI.
Takemoto
Nobuyuki
N
Department of Surgery, Omiya Medical Center, Jichi Medical School, Saitama, Japan. ns-take@hh.iij4u.or.jp
Konishi
Fumio
F
Yamashita
Keisuke
K
Kojima
Masayuki
M
Furukawa
Taiji
T
Miyakura
Yasuyuki
Y
Shitoh
Kazuhisa
K
Nagai
Hideo
H
D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009418:S100 Proteins / Q000032:analysis; D015996:Survival Rate
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D009418:S100 Proteins