Stromal myofibroblasts predict disease recurrence for colorectal cancer.
OBJECTIVE
Myofibroblasts, which are specifically differentiated fibroblasts, are thought to play a central role in the desmoplastic reaction, a dynamic stromal change closely associated with cancer development. Although fundamental studies suggest that myofibroblasts may either facilitate or inhibit cancer progression, cumulative evidence supports their role in promoting tumor progression. The aim of this study was to assess the value of myofibroblasts in the cancer stroma as an indicator of disease recurrence after colorectal cancer surgery.


METHODS
Using computer-assisted image analysis, we quantified myofibroblasts in the cancer-associated stroma of 192 colorectal cancers using alpha-smooth muscle actin as a marker.


RESULTS
The cancer-associated stroma contained various numbers of myofibroblasts (0.35-19.0%; mean, 5.55 +/- 3.85%). Tumors with abundant myofibroblasts were associated with shorter disease-free survival rate (P = 0.001) for stage II and III colorectal cancer. Multivariate analysis indicated that alpha-smooth muscle actin was a significant prognostic factor comparable with lymph node metastasis and superior to other tumor and stromal components, including histology of the tumor invasive front, peritumoral lymphocytic infiltration, and Crohn's-like lymphoid reaction. Moreover, colorectal cancers with synchronous liver metastasis generally displayed an active desmoplastic reaction, which was retained in the metastatic lesion to a similar extent.


CONCLUSIONS
The results suggest that the abundance of myofibroblasts in cancer-associated stroma may be a useful indicator of disease recurrence after curative colorectal cancer surgery.
Tsujino
Tadashi
T
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, School of Allied Health Science, Faculty of Medicine, Osaka University, Osaka, Japan.
Seshimo
Iwao
I
Yamamoto
Hirofumi
H
Ngan
Chew Yee
CY
Ezumi
Koji
K
Takemasa
Ichiro
I
Ikeda
Masataka
M
Sekimoto
Mitsugu
M
Matsuura
Nariaki
N
Monden
Morito
M
D000199:Actins / Q000378:metabolism; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism
D000199:Actins; D014408:Biomarkers, Tumor