Absence of smooth muscle actin-positive pericyte coverage of tumor vessels correlates with hematogenous metastasis and prognosis of colorectal cancer patients.
OBJECTIVE
Immature microvessels, which are not covered by pericytes, are irregular and leaky. We hypothesized that tumor cells can penetrate immature microvessels more easily than mature microvessels. In this study, we investigated the maturation of angiogenesis by the immunohistochemical staining of colorectal cancer specimens and determined the correlation between the microvessel count or the maturity of microvessels and clinicopathological variables.


METHODS
Ninety-two surgical specimens from our department were used. Double immunostaining of endothelial cells with anti-CD34 antibody and pericytes with anti-alpha-smooth muscle actin antibody was performed. The microvessel density (MVD) and microvessel pericyte coverage index (MPI) as an index of microvessel maturation were evaluated.


RESULTS
The MVD showed a significant positive correlation with tumor size, depth of invasion and Dukes' stage. The MPI showed a significant positive correlation with the histological differentiation of the tumor tissues and distant metastasis at the time of operation. The high MVD group (> or =26.0, n = 50) tended to have a poorer prognosis than the low MVD group (<26.0, n = 42) (p = 0.097). Next, the 50 patients in the high MVD group were classified into two subgroups of high MPI (> or =78.1%, n = 25) and low MPI (<78.1%, n = 25). MPI showed a significant negative correlation with hematogenous metastasis, and the low MPI group demonstrated a significantly poorer survival than the high MPI group (p = 0.040).


CONCLUSIONS
These findings demonstrate that immature neovascularization was observed in poorly differentiated tumors and was correlated with metastasis, resulting in a poorer prognosis. Taken together, not only microvessel density but also vascular maturation were crucial factors for colorectal cancer patients.
Yonenaga
Yoshikuni
Y
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan. yoney@kuhp.kyoto-u.ac.jp
Mori
Akira
A
Onodera
Hisashi
H
Yasuda
Seiichi
S
Oe
Hideaki
H
Fujimoto
Akihisa
A
Tachibana
Tsuyoshi
T
Imamura
Masayuki
M
D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000276:immunology; D002199:Capillary Permeability; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009360:Neoplastic Cells, Circulating; D009389:Neovascularization, Pathologic; D020286:Pericytes / Q000737:chemistry / Q000502:physiology; D011379:Prognosis; D016019:Survival Analysis
D000199:Actins; D018952:Antigens, CD34