Marked Prognostic Impact of Minimal Lymphatic Tumor Spread in Prostate Cancer

Wilczak, Waldemar; Wittmer, Corinna; Clauditz, Till S.; Minner, Sarah; Steurer, Stefan; Büscheck, Franziska; Krech, Till; Lennartz, Maximilian; Harms, Luisa; Leleu, Diane; Ahrens, Marc; Ingwerth, Sebastian; Günther, Christian T.; Koop, Christina; Simon, Ronald; Jacobsen, Frank; Tsourlakis, Maria Christina; Chirico, Viktoria; Höflmayer, Doris; Vettorazzi, Eik; Haese, Alexander; Steuber, Thomas; Salomon, Georg; Michl, Uwe; Budäus, Lars; Tilki, Derya; Thederan, Imke; Fraune, Christoph; Göbel, Cosima; Henrich, M.; Juhnke, Manuela; Möller, Katharina; Bawahab, Ahmed Abdulwahab; Uhlig, Ria; Adam, Meike; Weidemann, Sören; Becher, Burkhard; Huland, Hartwig; Graefen, Markus; Sauter, Guido; Schlomm, Thorsten

doi:10.1016/j.eururo.2018.05.034

Cited by 64 publications

(52 citation statements)

References 32 publications

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“…A recent study reported that the lymphovascular invasion of PCa cells has a significantly prognostic impact on disease progression. [40] Although we cannot provide the direct impact of SNP rs145204276 and the survival outcome, but considering the presence of lymph node metastasis after radical prostatectomy is a well-known poor prognostic factor with increased long-term risk of cancer specific mortality, estimated to range from 20% to 42% [41][42][43]. A worse cancer specific survival in patient with SNP rs145204276 might be a reasonable expectation, but further direct evidence to validate is still needed.…”

Section: Discussionmentioning

confidence: 91%

Impact of GAS5 genetic polymorphism on prostate cancer susceptibility and clinicopathologic characteristics

Lin¹,

Wang²,

Yang³

et al. 2019

Int. J. Med. Sci.

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Down-regulation of Growth arrest-specific 5 (GAS5) is correlated with enhanced cell proliferation and poorer prognosis of prostate cancer. We aimed to investigate the effect of variant rs145204276 of GAS5 on the prostate cancer susceptibility and clinicopathologic characteristics. In this study, 579 prostate cancer patients who underwent robot-assisted radical prostatectomy and 579 healthy controls were included. The frequency of the allele del of rs145204276 were compared between the patients and the controls to evaluate the impact of tumor susceptibility and the correlation of clinicopathological variables. The results shown that patients who carries genotype ins/del or del/del at SNP rs145204276 showed decreased risk of pathological lymph node metastasis disease (OR=0.545, p=0.043) and risk of seminal vesicle invasion (OR=0.632, p=0.022) comparing to with genotype ins/ins. In the subgroup analysis of age, more significant risk reduction effects were noted over lymph node metastasis disease (OR=0.426, p=0.032) and lymphovascular invasion (OR=0.521, p=0.025). In conclusion, the rs145204276 polymorphic genotype of GAS5 can predict the risk of lymph node metastasis. This is the first study to report the correlation between GAS5 gene polymorphism and prostate cancer prognosis.

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Section: Discussionmentioning

confidence: 91%

Impact of GAS5 genetic polymorphism on prostate cancer susceptibility and clinicopathologic characteristics

Lin¹,

Wang²,

Yang³

et al. 2019

Int. J. Med. Sci.

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show abstract

“…On the one hand, they promote tumor metastasis by providing malignant cells with an escape conduit for dissemination toward the lymph nodes and distal metastatic niches. Accordingly, the presence of lymphatic metastasis is correlated with poor patient prognosis and survival (Pasquali et al, 2013;Stacker et al, 2014;Wilczak et al, 2018). On the other side, the presence of functional lymphatics boosts anti-tumoral immune response and facilitates the delivery of chemotherapy agents enhancing their effect (Lund et al, 2016;Fankhauser et al, 2017;Song et al, 2020).…”

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confidence: 99%

Cellular Origins of the Lymphatic Endothelium: Implications for Cancer Lymphangiogenesis

Gutierrez-Miranda

Yaniv

2020

Front. Physiol.

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The lymphatic system plays important roles in physiological and pathological conditions. During cancer progression in particular, lymphangiogenesis can exert both positive and negative effects. While the formation of tumor associated lymphatic vessels correlates with metastatic dissemination, increased severity and poor patient prognosis, the presence of functional lymphatics is regarded as beneficial for anti-tumor immunity and cancer immunotherapy delivery. Therefore, a profound understanding of the cellular origins of tumor lymphatics and the molecular mechanisms controlling their formation is required in order to improve current strategies to control malignant spread. Data accumulated over the last decades have led to a controversy regarding the cellular sources of tumor-associated lymphatic vessels and the putative contribution of nonendothelial cells to this process. Although it is widely accepted that lymphatic endothelial cells (LECs) arise mainly from pre-existing lymphatic vessels, additional contribution from bone marrow-derived cells, myeloid precursors and terminally differentiated macrophages, has also been claimed. Here, we review recent findings describing new origins of LECs during embryonic development and discuss their relevance to cancer lymphangiogenesis.

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“…pN data are greatly influenced by the extent of surgery and the extent of pathological work-up of the removed materials. 62 The Gleason grading system suffers from marked interobserver variability reaching close to 40%. 63,64 This not only applies for nonspecialized pathologists but also for experts.…”

Section: Discussionmentioning

confidence: 99%

High B7‐H3 expression is linked to increased risk of prostate cancer progression

Bonk

Tasdelen

Kluth

et al. 2020

Pathology International

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B7-H3 is a member of the B7 superfamily of immune checkpoint molecules. B7-H3 up regulation has been linked to cancer development and progression in many tumors including prostate cancer. To clarify the potential utility of B7-H3 as a prognostic biomarker, B7-H3 expression was analyzed by immunohistochemistry in more than 17 000 prostate cancers. Normal prostatic glands were largely B7-H3 negative, while membranous B7-H3 immunostaining was seen in 47.0% of analyzed cancers. B7-H3 immunostaining was weak in 12.3%, moderate in 21.1% and strong in 13.5% of cases. High B7-H3 expression was associated with pT, Gleason score, lymph node metastasis, high Ki67 labeling index and early prostate-specific antigen recurrence (P < 0.0001 each). High B7-H3 expression was also linked to high androgen receptor expression and TMPRSS2:V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusions (P < 0.0001 each). Multivariate analyses showed a strong independent prognostic impact of high B7-H3 expression in all cancers and in the ERG negative subgroup. Comparison with previously analyzed frequent chromosomal deletions revealed a close association with Phosphatase and Tensin Homolog deletions. Analysis of B7-H3, alone or in combination with other markers, might be of clinical utility, especially in the subgroup of ERG negative prostate cancers.

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Marked Prognostic Impact of Minimal Lymphatic Tumor Spread in Prostate Cancer

Cited by 64 publications

References 32 publications

Impact of GAS5 genetic polymorphism on prostate cancer susceptibility and clinicopathologic characteristics

Impact of GAS5 genetic polymorphism on prostate cancer susceptibility and clinicopathologic characteristics

Cellular Origins of the Lymphatic Endothelium: Implications for Cancer Lymphangiogenesis

High B7‐H3 expression is linked to increased risk of prostate cancer progression

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