Lymphangiogenesis as a Prognostic Marker in Breast Cancer Using D2-40 as Lymphatic Endothelial Marker—A Preliminary Study
- 1 Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
- 2 Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
- 3 Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
- 4 Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
- 5 Department of Biostatistics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
- 6 Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Abstract
We studied tumour lymphangiogenesis and lymphatic invasion using D2-40 endothelial marker in 35 breast cancer patients treated by primary surgery and correlated it with various clinico-pathological prognostic parameters. Lymphangiogenesis was quantified using lymphatic micro vessel density (LMVD) by counting the immunostained lymphatic microvessels at 200X. The mean age was 45.97±12.09 years (range 30-80 years). LMVD ranged from 5/hpf to 56/hpf with a mean score of 13.4±10.8 and median of 9. The median value of 9 was taken to classify patients into a low or high LMVD. LMVD correlated significantly with tumour size (p=0.003), histological grade (p=0.046), lymph node status (p=0.030). There was no significant correlation of LMVD with stage, estrogen receptor, progesterone receptor or HER2/neu immunoreactivity. Lymphovascular invasion on D2-40 staining [LVI-D40] was found in 13 (37.1%) cases compared to 6 cases (17.1%) on H & E staining showing a poor agreement (k=0.244). LVI correlated significantly with lymph node status (p=0.011). There was a strong association between tumour size (p=0.142), histological grade (p=0.066) though the correlation was not statistically significant. No correlation was found with stage, estrogen receptor, progesterone receptor or HER2/neu immunoreactivity. The mean LMVD in LVI positive patients was higher (22.85±13.29) as compared to LVI negative patients (7.95±2.05) and this was statistically significant (p=0.001). Increased D2-40 detected LMVD and LVI correlated with poor prognostic parameters.
- E. R. Fisher, et al., “Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) Protocol B-17: Intraductal Carcinoma (Ductal Carcinoma in Situ),” Cancer, Vol. 75, No. 6, 1995, pp. 1310-1319. doi:10.1002/1097-0142(19950315)75:6 3.0.CO;2-G
- P. A. Kyzas, et al., “Evidence for Lymphangiogenesis and Its Prognostic Implications in Head and Neck Squamous Cell Carcinoma,” Journal of Pathology, Vol. 206, No. 2, 2005, pp. 170-177. doi:10.1002/path.1776
- K. Schmid, et al., “Prognostic Value of Lymphatic and Blood Vessel Invasion in Neuroendocrine Tumours of the Lung,” The American Journal of Surgical Pathology, Vol. 29, 2005, pp. 324-328. doi:10.1097/01.pas.0000149706.74216.b6
- P. Bono, et al., “High LYVE-1-Positive Lymphatic Vessel Numbers Are Associated with Poor Outcome in Breast Cancer,” Clinical Cancer Research, Vol. 10, No. 21, 2004, pp. 7144-7149. doi:10.1158/1078-0432.CCR-03-0826
- C. S. M. Williams, et al., “Absence of Lymphangiogenesis and Intratumoural Lymph Vessels in Human Metastatic Breast Cancer,” The Journal of Pathology, Vol. 200, 2003, pp. 195-206. doi:10.1002/path.1343
- H. J. Kahn, et al., “Monoclonal Antibody D2-40, a New Marker of Lymphatic Endothelium, Reacts with Kaposi’s Sarcoma and a Subset of Angiosarcomas,” Modern Pathology, Vol. 15, No. 4, 2002, pp. 434-440. doi:10.1038/modpathol.3880543
- N. Weidner, et al., “Tumour Angiogenesis and Metastasis—Correlation in Invasive Breast Carcinoma,” The New England Journal of Medicine, Vol. 324, No. 1, 1991, pp. 1-8. doi:10.1056/NEJM199101033240101
- R. G. C. Dumitrescu, “Understanding Breast Cancer Risk Where Do We Stand in 2005?” Journal of Cellular and Molecular Medicine, Vol. 9, No. 1, 2005, pp. 208-221. doi:10.1111/j.1582-4934.2005.tb00350.x
- A. J. Leu, et al., “Absence of Functional Lymphatics within a Murine Sarcoma: A Molecular and Functional Evaluation,” Cancer Research, Vol. 60, No. 16, 2000, pp. 4324-4327.
- M. Skobe, et al., “Induction of Tumour Lymphangiogenesis by VEGF-C Promotes Breast Cancer Metastasis,” Nature Medicine, Vol. 7, No. 16, 2001, pp. 192-198. doi:10.1038/84643
- S. J. Mandriota, et al., “Vascular Endothelial Growth Factor-C Mediated Lymphangiogenesis Promotes Tumour Metastasis,” The EMBO Journal, Vol. 72, No. 20, 2001, pp. 672-682. doi:10.1093/emboj/20.4.672
- Y. He, et al., “Suppression of Tumour Lymphangiogenesis and Lymph Node Metastasis by Blocking Vascular Endothelial Growth Factor Receptor 3 Signaling,” Journal of the National Cancer Institute, Vol. 94, No. 11, 2002, pp. 819-825. doi:10.1093/jnci/94.11.819