Intratumoral α-SMA enhances the prognostic potency of CD34 associated with maintenance of microvessel integrity in hepatocellular carcinoma and pancreatic cancer.
Microvessel density (MVD) as an angiogenesis predictor is inefficient per se in cancer prognosis. We evaluated prognostic values of combining intratumoral alpha-smooth muscle actin (α-SMA)-positive stromal cell density and MVD after curative resection in hypervascular hepatocellular carcinoma (HCC) and hypovascular pancreatic cancer (PC). Tissue microarrays were constructed from tumors of 305 HCC and 57 PC patients who underwent curative resection and analyzed for α-SMA and CD34 expression by immunostaining. Prognostic values of these two proteins and other clinicopathological features were examined. Both low α-SMA density and high MVD-CD34 were associated in HCC with the presence of intrahepatic metastasis and microvascular invasion, and they were related to lymph node involvement and microvascular invasion in PC (p<0.05). Although CD34 alone, but not α-SMA, was an independent prognostic factor for overall survival and recurrence-free survival, the combination of low α-SMA and high CD34 was a predictor of worst prognosis for both types of tumors and had a better power to predict patient death and early recurrence (p<0.01). Furthermore, the results show that distribution of most of the α-SMA-positive cells and vascular endothelial cells overlap, showing major colocalization on vascular walls. Poor microvessel integrity, as indicated by high MVD, together with low perivascular α-SMA-positive cell coverage is associated with early recurrence, unfavorable metastasis, and short survival after tumor resection. This finding highlights the significance of vascular quality in tumor progression, which provides an optimized complement to vascular quantity in prognosis of postoperative patients.
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Wen-Quan
WQ
Wang
Liang
L
Liu
Hua-Xiang
HX
Xu
Guo-Pei
GP
Luo
Tao
T
Chen
Chun-Tao
CT
Wu
Yong-Feng
YF
Xu
Jin
J
Xu
Chen
C
Liu
Bo
B
Zhang
Jiang
J
Long
Zhao-You
ZY
Tang
Xian-Jun
XJ
Yu
D000199:Actins / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D002452:Cell Count; D015331:Cohort Studies; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D055806:Microvessels / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis
C541116:ACTA2 protein, human; D000199:Actins; D018952:Antigens, CD34; D014408:Biomarkers, Tumor