Significance of PGP9.5 expression in cancer-associated fibroblasts for prognosis of colorectal carcinoma.
To assess the expression of a cancer-associated fibroblasts (CAFs) marker as an indicator of prognosis, we raised anti-protein gene product 9.5 (PGP9.5) monoclonal antibody against cultured fibroblasts. PGP9.5 expression in cultured normal fibroblasts was increased by transforming growth factor beta stimulation, indicating the phenotypic alteration to activated fibroblast. We immunohistochemically evaluated PGP9.5 expression with the CAFs of 110 colorectal cancer cases under T3 stage. PGP9.5 immunoreactivity in 30% or more of CAFs was defined as high PGP9.5 expression, and the other cases were considered as having low PGP9.5 expression. Patients with high PGP9.5 expression (42.7%) had significantly shorter survival and a higher incidence of recurrence than the low PGP9.5 expression group (P = .002 and P < .001, respectively). Multivariate analysis indicated PGP9.5 expression as an independent prognostic factor for overall and recurrence-free survival partly as well as lymph node metastasis. These results indicate that PGP9.5 expression in CAFs is a helpful finding to represent the overall biologic behavior of advanced colorectal cancer.
Akishima-Fukasawa
Yuri
Y
National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Ino
Yoshinori
Y
Nakanishi
Yukihiro
Y
Miura
Ayaka
A
Moriya
Yoshihiro
Y
Kondo
Tadashi
T
Kanai
Yae
Y
Hirohashi
Setsuo
S
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007564:Japan / Q000453:epidemiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D043222:Ubiquitin Thiolesterase / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D016212:Transforming Growth Factor beta; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase