TMEM (Tumor MicroEnvironment of Metastasis) in Human Breast Cancer: An Intravasation Microenvironment Unrelated to Intratumoral Lymphatics
Paula S Ginter, Brian D Robinson, Timothy M D'Alfonso, Maja H Oktay, Joan G Jones. WCMC, New York, NY; Albert Einstein Coll. of Med., Bronx, NY
Background: Metastasis is a major cause of mortality in patients with breast carcinoma; however the assessment of metastatic risk is imprecise. Previously, we identified and quantitated an intravasation microenvironment which we call TMEM (Tumor MicroEnvironment of Metastasis) (Wyckoff et al. Cancer Res. 2007). TMEM is defined as the direct apposition of a Mena-expressing invasive carcinoma cell, a perivascular macrophage, and an endothelial cell. In a case control study of 60 patients, with matched pairs differing only in their metastatic status, the density of TMEM was assessed and showed a significant association with development of systemic, hematogenous metastasis (p = 0.00006) (Robinson et al. Clin. Cancer Res. 2009). As lymph node status is considered an important prognostic factor in breast cancer, we aimed to 1) assess intratumoral lymphatic density in this same cohort, 2) determine if TMEM-like structures involving lymphatics exist, and 3) determine if TMEM-like structures are correlated with metastatic risk.
Design: All cases from the Robinson et al. cohort were stained in the same manner as the original study with the exception of using D2-40 (a lymphatic marker) instead of CD31 (a vascular marker). The marker for macrophages (CD68) and invasive tumor cells (Mena) remained the same. Two pathologists, blinded to outcome, evaluated the presence or absence of intratumoral lymphatics and quantitated the number of TMEM-like structures per 10 high power (400x) fields in areas of highest intratumoral lymphatic density. A TMEM-like structure was defined as the direct apposition of a lymphatic endothelial cell with a macrophage and invasive tumor cell.
Results: The majority of tumors in each of the 2 groups contained no intratumoral lymphatics (18 of 30 in the non-metastatic group, 16 of 30 in the metastatic group; p=0.6). TMEM-like structures were rare and were present in equal numbers in the 2 groups (3 metastatic and 3 non-metastatic cases). Using the Wilcoxon (paired) signed-rank test, we found no significant difference in the density of these structures between the two groups (p = 0.4). Furthermore, TMEM-like structures did not correlate with the presence of lymph node metastases (p=0.8).
Conclusions: Lymphatic vessels do not participate in the TMEM assembly that has been associated with hematogenous metastasis. TMEM density assessment reflects a hematogenous intravasation microenvironment and offers a novel approach to the assessment of metastatic risk.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 283, Wednesday Morning