Tumor lymphangiogenesis in transitional cell carcinoma of the upper urinary tract: association with clinicopathological features and prognosis.
OBJECTIVE
Lymph node metastasis is an important prognostic factor in many types of cancer. Recently several specific markers for lymphatic endothelium were developed that facilitate the quantification of lymphangiogenesis in human cancer tissues. We investigated the clinical and prognostic significance of lymphangiogenesis in patients with transitional cell carcinoma of the upper urinary tract.


METHODS
We measured lymph vessel density and relative lymphatic vascular area in 125 specimens by quantitative immunohistochemical staining for D2-40 antibody (DakoCytomation, Glostrup, Denmark). These parameters were examined in the intratumor and peritumor areas, and measured using image analysis software.


RESULTS
Peritumor lymph vessel density and peritumor lymphatic vascular area correlated with lymph node metastasis and tumor grade. In the intratumor area lymphatic vessels were detected in only 16.0% of specimens. However, the presence of intratumor lymphatic vessels was associated with lymph node metastasis (p = 0.002). Multivariate analysis identified high peritumor lymphatic vascular area and the presence of intratumor lymphatic vessels as significant and independent factors of metastasis-free survival after surgery (OR = 5.11, p = 0.020 and OR = 2.92, p = 0.025, respectively). Multivariate analysis also identified the presence of intratumor lymphatic vessels as the only independent predictive factor of cause specific survival (OR = 3.89, p = 0.049).


CONCLUSIONS
Lymphangiogenesis may have important roles in tumor metastasis and survival in patients with transitional cell carcinoma of the upper urinary tract. Quantification of lymphatic vessels, especially peritumor lymphatic vascular area and intratumor lymphatic vessels, was useful for predicting metastasis-free survival. In addition, the presence of intratumor lymphatic vessels was an independent predictor of cause specific survival.
Miyata
Yasuyoshi
Y
Department of Urology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan. int.doc.miya@m3.dion.ne.jp
Kanda
Shigeru
S
Ohba
Kojiro
K
Nomata
Koichiro
K
Eguchi
Jiro
J
Hayashida
Yasushi
Y
Kanetake
Hiroshi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology*; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D014516:Ureteral Neoplasms / Q000401:mortality / Q000473:pathology*