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

Puła, Bartosz; Jethon, Aleksandra; Piotrowska, Aleksandra; Gomułkiewicz, Agnieszka; Owczarek, Tomasz B.; Calik, Jacek; Wojnar, Andrzej; Witkiewicz, Wojciech; Ryś, Janusz; Ugorski, Maciej; Dzięgiel, Piotr; Podhorska-Okołów, Marzena

doi:10.1111/j.1365-2559.2011.04060.x

Cited by 87 publications

(107 citation statements)

References 36 publications

(129 reference statements)

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“…Moreover, expression of this marker was noted in myoepithelial cells and in stromal cancer-associated fibroblasts, what is in accordance with other authors studies [2][3][4][5][6][7][8][9][12][13][14][15][16][17]. Selected vessels were double-stained with CD34 and podoplanin.…”

Section: Discussionsupporting

confidence: 76%

“…Other authors found similar relations between the above-mentioned parameter and grade, ER/PR/HER2 expression and tumour cells proliferation [16][17][18]. This result suggests the existence of a specific subpopulation of stroma cancer-associated fibroblasts with podoplanin expression that may stimulate (or may be associated with) aggressive behaviour of cancer cells.…”

Section: Discussionsupporting

confidence: 61%

“…In each field, vessels were marked manually and then counted automatically. Eventually, LVD and MVD were calculated as the mean number of vessels per mm 2 (modified Weidner method [10,11,16]). Finally, the LVD/MVD ratio was calculated.…”

Section: Ihc Evaluationmentioning

confidence: 99%

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Lymphangiogenesis assessed using three methods is related to tumour grade, breast cancer subtype and expression of basal marker

Niemiec¹,

Adamczyk²,

Ambicka³

et al. 2012

pjp

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Lymphangiogenesis is a potential indicator of cancer patients' survival. However, there is no standardisation of methodologies applied to the assessment of lymphatic vessel density. In 156 invasive ductal breast cancers (T ≥ 1/N+/M0), lymphatic and blood vessels were visualised using podoplanin and CD34, respectively. Based on these markers expression, four parameters were assessed: (i) distribution of podoplanin-stained vessels (DPV) -the percentage of fields with at least one lymphatic vessel (a simple method proposed by us), (ii) lymphatic vessel density (LVD), (iii) LVD to microvessel density ratio (LVD/MVD) and (iv) the expression of podoplanin in cancer-associated fibroblasts. Next, we estimated relations between the above-mentioned parameters and: (i) breast cancer subtype, (ii) tumour grade, and (iii) basal markers expression. We found that intensive lymphangiogenesis, assessed using all studied methods, is positively related to high tumour grade, triple negative or HER2 subtype and expression of basal markers. Whereas, the absence of podoplanin expression in fibroblasts of cancer stroma is related to luminal A subtype, low tumour grade or lack of basal markers expression. Distribution of podoplanin-stained vessels, assessed by a simple method proposed by us (indicating the percentage of fields with at least one lymphatic vessel), might be used instead of the "hot-spot" method.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionsupporting

confidence: 61%

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Lymphangiogenesis assessed using three methods is related to tumour grade, breast cancer subtype and expression of basal marker

Niemiec¹,

Adamczyk²,

Ambicka³

et al. 2012

pjp

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“…The above phenomena were confirmed by studies in which the following stroma-related parameters were found to be of prognostic significance: (i) tumor-tostroma ratio (5-7); (ii) the type of tumor stroma (fibroblastdominant vs. lymphatic-dominant vs. collagen-dominant) (8-10); (iii) the presence of podoplanin-positive CAFs (ppCAFs) (11)(12)(13)(14) . Furthermore, it was suggested that CAFs might contribute to: (i) tumor initiation; (ii) proliferation, migration and invasiveness of cancer cells; (iii) tumor angiogenesis/lymphangiogenesis; (iv) tumor-induced inflammation; (v) metabolic reprogramming of the tumor microenvironment; and (vi) therapeutic resistance (4).…”

supporting

confidence: 52%

Podoplanin-positive Cancer-associated Stromal Fibroblasts in Primary Tumor and Synchronous Lymph Node Metastases of HER2-overexpressing Breast Carcinomas

Niemiec

Adamczyk

Harazin-Lechowska

et al. 2018

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Numerous studies have shown that cancer development and metastasis formation are complex processes which involve not only cancer cells but also their interaction with selected components of tumor stroma. According to the seed and soil hypothesis, a permissive microenvironment (soil) facilitates growth of metastatic cancer cells (seed) in secondary sites. It was shown that stromal components (including cancerassociated fibroblasts, CAFs) can travel together with metastatic cells from the primary to secondary site. Moreover, co-traveling stromal cells can increase the viability of circulating metastatic cancer cells and provide them with an early growth advantage (1). It was also shown that CAFs promote tumor invasion by exerting a physical force on cancer cells, enabling them to escape from the primary site (2) . The identification of CAFs in peripheral blood from patients with metastatic breast cancer confirms the hypothesis suggesting co-travel of stromal and cancer cells during formation of metastases (3).In vitro studies and research based on animal models suggest a very important role of the cancer stroma in tumor progression (1, 4). The above phenomena were confirmed by studies in which the following stroma-related parameters were found to be of prognostic significance: (i) tumor-tostroma ratio (5-7); (ii) the type of tumor stroma (fibroblastdominant vs. lymphatic-dominant vs. collagen-dominant) (8-10); (iii) the presence of podoplanin-positive CAFs (ppCAFs) (11)(12)(13)(14) . Furthermore, it was suggested that CAFs might contribute to: (i) tumor initiation; (ii) proliferation, migration and invasiveness of cancer cells; (iii) tumor angiogenesis/lymphangiogenesis; (iv) tumor-induced inflammation; (v) metabolic reprogramming of the tumor microenvironment; and (vi) therapeutic resistance (4). Among many CAF-related proteins, podoplanin is one of the most intensively studied (8,9,(15)(16)(17) . Among breast cancer immunophenotypes, the human epidermal growth factor receptor 2 (HER2)-overexpressing subtype is the one in which ppCAFs were found to be relatively frequent (11).This prompted us to analyze: (i) the status of ppCAFs in primary tumor and paired synchronous lymph node metastases (LNMs); (ii) relation between ppCAFs in tumor

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“…Ovaries (2) Epidermis basal layer Honma et al (2012); Gandarillas et al (1997) (1), (2), (3), (4), (5), (6), (7), (8) Kawase et al (2008) Squamous lung carcinoma -(2), Kitano et al (2010) Breast cancer Poor (3) Pula et al (2011) Intrahepatic cholangiocarcinoma Poor…”

Section: Acknowledgementsmentioning

confidence: 99%

New Insights into the Role of Podoplanin in Epithelial–Mesenchymal Transition

Renart

Carrasco-Ramírez

Fernández‐Muñoz³

et al. 2015

International Review of Cell and Molecular Biology

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

Abstract: Our results suggest that podoplanin expression by CAFs could be an unfavourable prognostic marker for IDC.

Cited by 87 publications

References 36 publications

Lymphangiogenesis assessed using three methods is related to tumour grade, breast cancer subtype and expression of basal marker

Lymphangiogenesis assessed using three methods is related to tumour grade, breast cancer subtype and expression of basal marker

Podoplanin-positive Cancer-associated Stromal Fibroblasts in Primary Tumor and Synchronous Lymph Node Metastases of HER2-overexpressing Breast Carcinomas

New Insights into the Role of Podoplanin in Epithelial–Mesenchymal Transition

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