The biology and prognostic value of lymphatic vessel density (LD) and lymphatic invasion (LI) in regression in melanoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9017-9017
Author(s):  
S. Yun ◽  
P. Gimotty ◽  
W. Hwang ◽  
P. Dawson ◽  
P. VanBelle ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Value ◽  
Lymphatic Vessels ◽  
Tumor Infiltrating Lymphocytes ◽  
Lymphocytic Infiltration ◽  
Melanoma Cells ◽  
Lymphatic Invasion ◽  
Complete Regression ◽  
Cox Models ◽  
Vertical Growth Phase

9017 Background: Regression in melanoma is characterized by increased vascularity, lymphocytic infiltrate and fibroplasia in the papillary dermis, accompanied by the absence (complete regression, CoR) or presence (partial regression, PaR) of melanoma cells in the epidermis. The prognostic value of regression is controversial. We noticed that LD and LI were increased in the areas of regression (AR) or areas with brisk lymphocytic infiltration (AB). Our goal was to clarify the prognostic value of regression in melanoma. Methods: Dual immunohistochemical staining was done using antibodies to podoplanin (lymphatic vessels) and S100 (melanoma cells) on paraffin tissues from 321 patients with vertical growth phase (VGP) primary melanomas who had 10 years or more of follow-up. LD in AR (both CoR and PaR) was compared with that of normal dermis adjacent and distant, as well as LD in the AB. LI in these areas was also scored. Unadjusted and adjusted hazard rates were obtained from univariate and multivariate Cox models for time to melanoma-specific death using established melanoma prognostic factors. Results: 116 patients (36%) had regression: 75 CoR (23%) and 41 PaR (13%). LD significantly decreased stepwise from CoR (mean ± se, 23.7 ± 2.7) to PaR (15.5 ± 1.1), adjacent normal dermis (7.3 ± 0.28) and distant normal dermis (5.4±0.31) and it was significantly elevated in the AB (18.5±0.78). Melanomas with CoR had the highest percentage of LI in both AR and AB. In addition, the percentage of LI in AB was highest for men and for those with VGP tumor infiltrating lymphocytes (TILs). Both high LD in AR and more LI in AB were associated with poor prognosis (p=0.004 and p=0.002, respectively). Six factors were significant in the final multivariate model: LI in AB (HR=2.3), LD in AR (HR=1.04), thickness (HR=1.44), axial (HR=7.7), ulceration (HR=2.5) and no VGP TILs (HR=2.8). Conclusions: AR and AB were associated with increased LD and higher incidence of LI in primary melanomas. LD and LI in AR or AB are independent prognostic factors. Our data suggest that the effects of regression on prognosis are mediated at least in part through lymphangiogenesis and LI. No significant financial relationships to disclose.

Protective effect of a brisk tumor infiltrating lymphocyte infiltrate in melanoma: An EORTC melanoma group study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8519-8519 ◽  
Author(s):  
A. Spatz ◽  
P. A. Gimotty ◽  
M. G. Cook ◽  
J. J. van den Oord ◽  
N. Desai ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Cox Model ◽  
Tumor Infiltrating Lymphocytes ◽  
Good Prognosis ◽  
Small Population ◽  
Independent Prognostic Factor ◽  
Anatomic Site ◽  
Chi Square ◽  
Cox Models ◽  
Vertical Growth Phase

8519 Background: Tumor-infiltrating lymphocytes (TILs) in melanoma are responsible for tumor killing and may induce spontaneous regression. Brisk TILs in the melanoma vertical growth phase (VGP) is a strong, albeit not independent, prognostic factor associated with superior survival. This study investigated whether more detailed classes of TIL patterns, based on topography and intensity, are independent prognostic factors and identify patients with good prognosis. Methods: The study included 1,171 patients with cutaneous VGP melanoma with at least 3 years of follow up for whom slides were available for review. TIL infiltrate was assessed for pattern (absent, non brisk, brisk), intensity (scanty, moderate, dense), and topography (peripheral, central, both). Pattern was assessed qualitatively: brisk TIL infiltrate was defined as a continuous band of lymphocytes at the base of the melanoma, or throughout the tumor. Other studied variables were: thickness, mitotic count (MC), ulceration, gender, age, anatomic site, melanoma-related death (MRD). Subsequently, Chi-square tests, Kaplan-Meier curves (KM), logrank tests, and Cox models were applied to examine the relation between MRD, TIL categories and interaction with other variables. Results: A brisk infiltrate was observed in 21.2% of the cases. Adjusted hazard ratio for MRD as compared to the absent category was 0.82 (95% CI=0.64–1.06) in the non-brisk category, and 0.43 (95% CI=0.28–0.68) in the brisk category. Based on the Cox model, brisk TIL was an independent prognostic factor for MRD (p<0.001) controlling for thickness, MC, ulceration, gender, age and site. Intensity was significantly associated with MRD for melanomas with peripheral and central brisk TILs (p=0.027) but not for other melanomas. Remarkably, no death was observed in the 5.5% of melanomas with dense, brisk TIL infiltrate at ten years. Conclusions: A brisk TIL pattern was shown to have prognostic value for MRD underscoring the importance of TILs in the outcome of VGP melanoma patients. Furthermore, we identified a small population of “super-responder” patients whose tumor was characterised by a continuous and dense TIL infiltrate and who did not display signs of tumor progression. No significant financial relationships to disclose.

On-treatment changes in tumor-infiltrating lymphocytes (TIL) during neoadjuvant HER2 therapy (NAT) and clinical outcome.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 574-574 ◽  
Author(s):  
Stephen James Luen ◽  
Gaia Griguolo ◽  
Paolo Nuciforo ◽  
Christine Campbell ◽  
Roberta Fasani ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Immune Cell ◽  
Early Stage ◽  
Tumor Infiltrating Lymphocytes ◽  
Ratio Test ◽  
Cox Models ◽  
Immune Cell Subsets ◽  
Rnaseq Data ◽  
Treatment Changes ◽  
Infiltrating Lymphocytes

574 Background: Higher quantity of pretreatment TIL (PT) is associated with improved pCR and EFS in HER2+ early breast cancer (BC). The value of on-treatment TIL is unknown. Methods: The NeoALTTO trial randomized 455 women with HER2+ BC to 12 weeks NAT with trastuzumab, lapatinib or combination with paclitaxel, followed by FEC after surgery. In the PAMELA trial 151 women received 18 weeks NAT with lapatinib and trastuzumab (±hormonal therapy). TIL were quantified on PT and on-treatment (W2) biopsies using the published method on H&E slides, and tested for associations with pCR (logistic regression), EFS and OS (Cox models) in univariate (UV) and multivariate (MV) analyses. The likelihood ratio test assessed added prognostic value to clinicopathological (CP) variables. pCR associations were validated in PAMELA. We investigated enrichment of immune cell subsets using previously published RNAseq data from NeoALTTO. Results: In NeoALTTO, PT and W2 TIL were evaluable in 277/455 (61%). We defined two groups: immune-poor (L+F) and immune-enriched (II+P), see Table. Immune-enriched (41%; 134) vs poor (59%; 164) patients had significantly higher pCR rates (40% vs 21%; UV OR 2.24; 95%CI 1.31-3.85; P = .003; MV P = .009), and added significant value to CP + PT TIL for prediction of pCR (P = .003). This was further confirmed in PAMELA (N = 94/151) (26% vs 6%; UV P = .021; MV P = .028). In NeoALTTO, the immune-enriched vs poor patients had significantly improved EFS (5 yr est 85% vs 60%; UV HR 0.31; 95%CI 0.18-0.54; P < .001; MV P < .001) and OS (5 yr est 91% vs 77%; UV HR 0.40; 95%CI 0.20-0.82; P = .012; MV P = 0.026), and provided significant added prognostic value beyond CP + pCR + PT TIL (EFS P < .001) In NeoALTTO PT samples, II vs F patients had enrichment of DCs, NKs and CD8+ including tissue resident memory cells (P = .009) suggesting requirement of key immune subsets. Further validation by IHC is ongoing. Conclusions: On-treatment TIL identifies patients more likely to achieve pCR and have improved EFS in early-stage HER2+ BC, beyond CP + PT TIL. This information could aid future trial design. Clinical trial information: NCT00553358, NCT01973660. [Table: see text]

FACT physical wellbeing to independently predict overall survival in patients with acute myeloid leukemia.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7532-7532
Author(s):  
John Peipert ◽  
Fabio Efficace ◽  
Renee F. Pierson ◽  
Susan Yount ◽  
Christina Loefgren ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Prognostic Value ◽  
Intensive Therapy ◽  
Care Practice ◽  
Solid Cancer ◽  
Cox Models ◽  
Patient Reported ◽  
Physical Wellbeing

7532 Background: Patient-reported outcomes (PROs) predict overall survival (OS) in solid cancer populations, but little evidence exists around the prognostic value of PROs in patients with hematologic malignancies. We investigated whether scales from the Functional Assessment of Cancer Therapy – Leukemia (FACT-Leu) predicted OS beyond established prognostic factors. Methods: Data were from 317 AML patients unfit for intensive therapy from a clinical trial comparing Dacogen (decitabine) plus Talacotuzumab versus Dacogen (decitabine) alone (AML2002; NCT02472145). We used ridge-penalized Cox models to determine whether baseline (1st cycle) FACT-Leu scales predicted OS. FACT-Leu scales significant in these models and factors from a validated prognostic model, the AML composite model (AML-CL; covariates listed in Table), were entered into Cox proportional hazard models. Lastly, model selection procedures were run with 1000 bootstrapped samples using all variables. The inclusion frequency of each FACT-Leu scale in the final models was examined to evaluate prognostic value for OS (i.e., higher the % of inclusion, higher importance of the variable). Results: In the ridge-penalized Cox models, the Physical Wellbeing Scale (PWB), Trial Outcome Index (TOI), and FACT-Leu Total scales were significant predictors of OS. After adjusting for the AML-CL factors, an important difference (2 pts) in PWB score was associated with a 9% decline in OS. (Table) Model validity was evidenced as the PWB scale appeared in a large majority of selected models (90%-97%), while the TOI (45%-73%) and FACT-Leu Total (41%-71%) appeared less often. Conclusions: FACT-Leu scales, especially the PWB, were significant prognostic factors for OS among AML patients not suitable for intensive therapy. These results may indicate PROs' value as stratification factors in trials with AML patients and underscore the need to more systematically collect PRO data in routine care practice with AML patients. Clinical trial information: NCT02472145 . [Table: see text]

Prognostic value of De Ritis ratio (aspartate transaminase/alanine transaminase) in patients with non-metastatic colorectal carcinoma [izmir oncology group(IZOG) study].

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16114-e16114
Author(s):  
Utku Oflazoglu ◽  
Temmuz Gurdal Insan ◽  
Yuksel Kucukzeybek ◽  
Umut Varol ◽  
Tarik Salman ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Lymph Node ◽  
Prognostic Value ◽  
Perineural Invasion ◽  
Surgical Margin ◽  
Lymph Node Involvement ◽  
Lymphatic Invasion ◽  
Tumor Localization ◽  
Node Involvement

e16114 Background: We aimed to assess the prognostic effect of preoperative De Ritis (aspartate aminotransaminase/Alanine aminotransaminase) ratio and pathological variables to find out whether it is an independent prognostic factor in patients with non-metastatic CRC. Methods: We retrospectively evaluated the patients who underwent curative surgery for non-metastatic CRC between 2006 and 2017. The potential prognostic value of De Ritis ratio was assessed by using a ROC curve analysis. The effect of the De Ritis ratio was analyzed by the Kaplan–Meier method and Cox regression hazard models for patients’ disease-free survival (DFS) and overall survival (OS). Results: We had 921 CRC patients in total. The univariate analysis demonstrated that low De-Ritis ratio and several well-established prognostic factors, including well-differentiated tumor,negative lymph node involvement, lymphatic invasion, perineural invasion and surgical margin, left tumor localization and early-stage tumor were good prognostic factors in terms of DFS and OS. On the multivariate analysis, De-Ritis ratio, lymph node involvement, perineural invasion status, surgical margin statusand tumor localization were independent prognostic factors for DFS [ De-Ritis ratio HR 0.468, 95% CI 0.358-0.613,p < 0.001]. We also found that De-Ritis ratio, degree of differentiation, lymphatic invasion status, perineural invasion statusand stage were independent prognostic factors for OS on multivariate analysis [ De-Ritis ratio HR 0.354, 95% CI 0.407-0.702, p < 0.001]. Conclusions: Our study first established a connection between the preoperative De-Ritis ratio and patients undergoing curative resection for non-metastatic colorectal cancer, suggesting that De-Ritis ratio was a simple, inexpensive, and easily measurable marker as a prognostic factor and may help to identify high-risk patients for treatment decisions.

scholarly journals Mechanisms and Clinical Significance of Tumor Lymphatic Invasion

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2585
Author(s):  
Noriki Fujimoto ◽  
Lothar C. Dieterich
Keyword(s):  
Tumor Cells ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Lymphatic Invasion ◽  
Malignant Cells ◽  
Single Tumor ◽  
Draining Lymph Nodes ◽  
Gain Access

Tumor-associated lymphatic vessels play an important role in tumor progression, mediating lymphatic dissemination of malignant cells to tumor-draining lymph nodes and regulating tumor immunity. An early, necessary step in the lymphatic metastasis cascade is the invasion of lymphatic vessels by tumor cell clusters or single tumor cells. In this review, we discuss our current understanding of the underlying cellular and molecular mechanisms, which include tumor-specific as well as normal, developmental and immunological processes “hijacked” by tumor cells to gain access to the lymphatic system. Furthermore, we summarize the prognostic value of lymphatic invasion, discuss its relationship with local recurrence, lymph node and distant metastasis, and highlight potential therapeutic options and challenges.

scholarly journals Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 486
Author(s):  
Juan P. Rodrigo ◽  
Mario Sánchez-Canteli ◽  
Fernando López ◽  
Gregory T. Wolf ◽  
Juan C. Hernández-Prera ◽  
...  
Keyword(s):  
Systematic Review ◽  
Squamous Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Value ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

The presence of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment has been demonstrated to be of prognostic value in various cancers. In this systematic review and meta-analysis, we investigated the prognostic value of TIL in laryngeal squamous cell carcinoma (LSCC). We performed a systematic search in PubMed for publications that investigated the prognostic value of TIL in LSCC. A meta-analysis was performed including all studies assessing the association between TIL counts in hematoxylin-eosin (HE)-stained sections, for CD8+ and/or CD3+/CD4+ TIL and overall survival (OS) or disease-free survival (DFS). The pooled meta-analysis showed a favorable prognostic role for stromal TIL in HE sections for OS (HR 0.57, 95% CI 0.36–0.91, p = 0.02), and for DFS (HR 0.56, 95% CI 0.34–0.94, p = 0.03). High CD8+ TIL were associated with a prolonged OS (HR 0.62, 95% CI 0.4–0.97, p = 0.04) and DFS (HR 0.73, 95% CI 0.34–0.94, p = 0.002). High CD3+/CD4+ TIL demonstrated improved OS (HR 0.32, 95% CI 0.16–0.9, p = 0.03) and DFS (HR 0.23, 95% CI 0.10–0.53, p = 0.0005). This meta-analysis confirmed the favorable prognostic significance of TIL in LSCC. High stromal TIL evaluated in HE sections and intra-tumoral and stromal CD3+, CD4+ and/or CD8+ TIL might predict a better clinical outcome.

scholarly journals The role of FoxP3+ regulatory T cells and IDO+ immune and tumor cells in malignant melanoma – an immunohistochemical study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Satu Salmi ◽  
Anton Lin ◽  
Benjamin Hirschovits-Gerz ◽  
Mari Valkonen ◽  
Niina Aaltonen ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Factors ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Positive Association ◽  
Tumor Stage ◽  
Melanoma Cells ◽  
Melanoma Progression

Abstract Background FoxP3+ Regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) participate in the formation of an immunosuppressive tumor microenvironment (TME) in malignant cutaneous melanoma (CM). Recent studies have reported that IDO expression correlates with poor prognosis and greater Breslow’s depth, but results concerning the role of FoxP3+ Tregs in CM have been controversial. Furthermore, the correlation between IDO and Tregs has not been substantially studied in CM, although IDO is known to be an important regulator of Tregs activity. Methods We investigated the associations of FoxP3+ Tregs, IDO+ tumor cells and IDO+ stromal immune cells with tumor stage, prognostic factors and survival in CM. FoxP3 and IDO were immunohistochemically stained from 29 benign and 29 dysplastic nevi, 18 in situ -melanomas, 48 superficial and 62 deep melanomas and 67 lymph node metastases (LNMs) of CM. The number of FoxP3+ Tregs and IDO+ stromal immune cells, and the coverage and intensity of IDO+ tumor cells were analysed. Results The number of FoxP3+ Tregs and IDO+ stromal immune cells were significantly higher in malignant melanomas compared with benign lesions. The increased expression of IDO in melanoma cells was associated with poor prognostic factors, such as recurrence, nodular growth pattern and increased mitotic count. Furthermore, the expression of IDO in melanoma cells was associated with reduced recurrence˗free survival. We further showed that there was a positive correlation between IDO+ tumor cells and FoxP3+ Tregs. Conclusions These results indicate that IDO is strongly involved in melanoma progression. FoxP3+ Tregs also seems to contribute to the immunosuppressive TME in CM, but their significance in melanoma progression remains unclear. The positive association of FoxP3+ Tregs with IDO+ melanoma cells, but not with IDO+ stromal immune cells, indicates a complex interaction between IDO and Tregs in CM, which demands further studies.

scholarly journals Prognostic value of CD8CD45RO tumor infiltrating lymphocytes in patients with extrahepatic cholangiocarcinoma

Oncotarget ◽  
2018 ◽  
Vol 9 (34) ◽  
pp. 23366-23372 ◽  
Author(s):  
Richard Kim ◽  
Domenico Coppola ◽  
Emilie Wang ◽  
Young Doo Chang ◽  
Yuhree Kim ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Tumor Infiltrating Lymphocytes ◽  
Extrahepatic Cholangiocarcinoma ◽  
Infiltrating Lymphocytes
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