Clinical significance of nuclear morphometry at the invasive front of T1 colorectal cancer and relation to expression of VEGF-A and VEGF-C.
OBJECTIVE
To better understand the metastatic potential of T1 colorectal cancer, we investigated variations in nuclear morphometry and expression of angiogenic factors in cancer cells at the invasive front. Sixty-five patients who had undergone curative resection were entered.


METHODS
Nuclear shape factor, area, width, and proportion of cells with large nucleoli in all cells were determined in two high-power magnification areas at the invasive front of the tumor. We then performed the Ward method for cluster analysis. A dendrogram revealed that cases fell into two clusters: cluster A with high atypical nuclei and cluster B with low atypical nuclei. Expression of vascular endothelial growth factor-A (VEGF-A) and -C were evaluated immunohistochemically at the invasive front of the tumor.


RESULTS
Nuclear atypia, and VEGF-C expression were associated significantly with lymph node metastasis by univariate analysis. Nuclear atypia was independently and significantly associated with lymph node metastasis by multivariate analysis. Whereas VEGF-A expression was associated with nuclear atypia, VEGF-C expression was not showed. Nuclear atypia, strong VEGF-A or -C expressions were not associated with the depth of invasion.


CONCLUSIONS
Nuclear morphometry and expression of angiogenic factors at the invasive front are useful prognostic markers of lymph node metastasis, even cases with slight invasion.
Kojima
Motohiro
M
First Department of Pathology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan. motohiro@med.showa-u.ac.jp
Shiokawa
Akira
A
Ohike
Nobuyuki
N
Ohta
Yoshiki
Y
Kato
Hirotaka
H
Iwaku
Kenji
K
Hayasi
Ryoji
R
Morohoshi
Toshio
T
D000328:Adult; D000368:Aged; D002467:Cell Nucleus / Q000737:chemistry / Q000473:pathology*; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis*
D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C