Podoplanin expression by cancer-associated fibroblasts predicts poor outcome in invasive ductal breast carcinoma

• Published in: Histopathology 2011-12, Vol.59 (6), p.1249-1260
• Main Authors: Pula, Bartosz, Jethon, Aleksandra, Piotrowska, Aleksandra, Gomulkiewicz, Agnieszka, Owczarek, Tomasz, Calik, Jacek, Wojnar, Andrzej, Witkiewicz, Wojciech, Rys, Janusz, Ugorski, Maciej, Dziegiel, Piotr, Podhorska-Okolow, Marzena
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Biomarkers, Tumor - analysis; breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; cancer-associated fibroblasts; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - mortality; Carcinoma, Ductal, Breast - pathology; Female; Fibroblasts - metabolism; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Kaplan-Meier Estimate; Mammary gland diseases; Medical sciences; Membrane Glycoproteins - analysis; Membrane Glycoproteins - biosynthesis; Middle Aged; Neoplasm Grading; Neoplasm Staging; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; podoplanin; Prognosis; Proportional Hazards Models; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Tumors
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2011.04060.x

Pula B, Jethon A, Piotrowska A, Gomulkiewicz A, Owczarek T, Calik J, Wojnar A, Witkiewicz W, Rys J, Ugorski M, Dziegiel P & Podhorska‐Okolow M 
(2011) Histopathology 59, 1249–1260 
Podoplanin expression by cancer‐associated fibroblasts predicts poor outcome in invasive ductal breast carcinoma Aims:  It has recently been shown that podoplanin, a mucin‐type glycoprotein, is expressed by cancer cells and cancer‐associated fibroblasts (CAFs), and promotes cancer cell migration and invasiveness. The biological role of podoplanin expression in tumour stroma of invasive ductal carcinoma of the breast (IDC) has not been determined. Methods and results:  Podoplanin expression was analysed in 117 cases of IDC and 27 cases of fibrocystic change, as well as in breast cancer cell lines, with the use of immunohistochemistry and real‐time polymerase chain reaction. In 82.1% of analysed tumours, podoplanin was found only in CAFs. Only two of 117 IDC cases (1.7%) were characterized by expression of this glycoprotein in cancer cells. None of the fibrocystic changes or stroma surrounding normal ducts showed podoplanin expression. Podoplanin‐positive CAFs correlated with tumour size (P = 0.0125), grade of malignancy (P = 0.0058), lymph node metastasis (P = 0.0149), lymphovascular invasion (LVI) (P = 0.0486) and Ki67 expression in cancer cells (P = 0.0128). High‐level podoplanin expression (>50% of positive stroma) in the tumour stroma was significantly associated with a negative oestrogen status (P = 0.0201). Univariate, but not multivariate, analysis showed that podoplanin expression by CAFs was associated with poor patient outcome (P = 0.0202). Conclusions:  Our results suggest that podoplanin expression by CAFs could be an unfavourable prognostic marker for IDC.