Podoplanin - Related Lymphatic Micro Vessel Density Digital Analysis in Breast Adenocarcinoma

Neo-lymphangiogenesis induces lymphatic invasion of cancer cells, significantly increasing the metastatic potential of breast carcinomas (BCs). Among the molecules that are implicated in lymphangiogenesis, podoplanin (PDPN, gene locus: 1p36.21) - a transmembrane receptor glycoprotein - is expressed exclusively in lymphatic vessels. The current study explored the impact of PDPN-dependent mean lymphatic micro-vessel density (mLMVD) in invasive ductal (inDBC) and invasive lobular breast adenocarcinomas (inLBC).

A set of thirty (n=30) paraffin-embedded invasive BC tissue sections (22 inDBCs and 8 inLBCs, respectively) were analyzed by applying a combination of immunocytochemistry (IHC) and digital image analysis (DIA) assays.

High and moderate mLMVD rates (defined by the mean number of lymphatic domains with emboli in five optical fields under 400X magnification) were detected in 5/30 (16.6%) and 6/30 (20%) cases (total 11/30 (36.6%), respectively. In these cases, PDPN demonstrated strong cytoplasmic/membranous staining intensity. The remaining 19 cases (63.4%) demonstrated low levels of mLMVD. mLMVD was significantly correlated with the stage of the examined malignancies (p=0.019), whereas a marginal association with the grade of differentiation was identified (p=0.042). No significant correlation was observed with histological subtype (p=0.234) or tumor size (p=0.085).

Neo-lymphangiogenesis in BCs is a critical histological feature in the progression of the malignancy and is correlated with an aggressive phenotype (advanced stage). PDPN expression in lymphatic micro vessels is a reliable biomarker for evaluating lymphangiogenic activity in BCs, independently of their histotype, especially when assessed with precise DIA techniques.