scholarly journals Combination of GP88 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Is an Independent Prognostic Factor for Bladder Cancer Patients

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1796
Author(s):  
Markus Eckstein ◽  
Verena Lieb ◽  
Rudolf Jung ◽  
Danijel Sikic ◽  
Katrin Weigelt ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Immune Cells ◽  
Potential Candidate ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Increased Risk ◽  
Muscle Invasive ◽  
Disease Specific

Urothelial bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide and accounts for approximately 3% of global cancer diagnoses. We are interested in prognostic markers that may characterize tumor cells (TCs) and immune cells (ICs) and their relationship in BCa. A potential candidate marker that meets these criteria is progranulin (GP88), which is expressed separately in TCs and ICs. We analyzed GP88 expression by immunohistochemistry (IHC) in 196 muscle-invasive BCa samples using a tissue microarray. The immunoreactive score for GP88 staining in TCs and the percentage of GP88-positive ICs was determined. An easy cutoff for the staining status of TCs (positive vs. negative) and ICs (0% vs. >0%) and, more generally, negative vs. positive GP88 staining could be applied. We detected 93 patients (47.4%) and 92 patients (46.9%) with GP88-positive TCs or ICs, respectively. The IHC results were correlated with clinicopathological and survival data. Positive GP88 staining in TCs appeared to be an independent poor prognostic factor for disease-specific survival (DSS) (RR (relative risk) = 1.74; p = 0.009) and recurrence-free survival (RFS) (RR = 1.92; p = 0.002). In contrast, negative GP88 staining in ICs was an independent negative predictor for overall survival (OS) (RR = 2.18; p < 0.001), DSS (RR = 2.84; p < 0.001) and RFS (RR = 2.91; p < 0.001) in multivariate Cox’s regression analysis. When combining GP88 staining in TCs and ICs, a specific combination of GP88-positive TCs and GP88-negative ICs was associated with a 2.54-fold increased risk of death, a 4.21-fold increased risk of disease-specific death and a 4.81-fold increased risk of recurrence compared to GP88-negative TCs and GP88-positive ICs. In summary, GP88 positivity in TCs is a negative prognostic factor for DSS and RFS. In addition, GP88 positivity can mark ICs that are associated with a good prognosis (OS, DSS and RFS). The combination of GP88 staining in TCs and ICs appears to be a significant independent prognostic biomarker in muscle-invasive BCa.

Prognostic impact of chemoradiation-related lymphopenia in patients with gastric and gastroesophageal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 249-249
Author(s):  
Daniel W Kim ◽  
Grace Lee ◽  
Theodore S. Hong ◽  
Guichao Li ◽  
Eric Roeland ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Cox Model ◽  
Gastroesophageal Junction ◽  
Concurrent Chemotherapy ◽  
Rank Test ◽  
Prognostic Impact ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Increased Risk ◽  
Ecog Ps

249 Background: Limited data exists on how chemoradiation (CRT)-induced lymphopenia affects survival outcomes in patients with gastric and gastroesophageal junction (GEJ) cancer. We evaluated the association between severe lymphopenia and its association with survival in gastric and GEJ cancer patients treated with CRT. We hypothesized that severe lymphopenia would be a poor prognostic factor. Methods: We performed a retrospective analysis of 154 patients with stage 1-3 gastric or GEJ cancer who underwent CRT at our institution. Patients underwent photon-based radiation therapy (RT) with a median dose of 50.4 Gy (IQR 45.0-50.4 Gy) over 28 fractions and concurrent chemotherapy (CTX) with carboplatin/paclitaxel, 5-fluorouracil based regimen, or capecitabine. 49% received CTX prior to RT. 84% underwent surgical resection, 57% pre-CRT and 26% post-CRT. Absolute lymphocyte count (ALC) at baseline and at 2 months since initiating RT were analyzed. Severe lymphopenia, defined as Grade 3 or worse lymphopenia (ALC < 0.5 k/μl), was analyzed for any association with overall survival (OS). Results: Median time of follow up was 48 months. Median age was 65. 77% were male and 86% were Caucasian. ECOG PS was 0 or 1 in 90% and 2 in 10%. Tumor location was stomach in 38% and GEJ in 62%. Timing of CRT was preoperative among 68% and postoperative among 32%. The median ALC at baseline for the entire cohort was 1.6 k/ul (range 0.3-7.0 k/ul). At 2 months post-CRT, 49 (32%) patients had severe lymphopenia. Patients with severe lymphopenia post-CRT had a slightly lower baseline TLC compared to patients without severe lymphopenia (median TLC 1.4 k/ul vs. 1.6 k/ul; p = 0.005). There were no differences in disease and treatment characteristics between the two groups. On the multivariable Cox model, severe lymphopenia post-CRT was significantly associated with increased risk of death (HR = 3.99 [95% CI 1.55-10.28], p = 0.004). ECOG PS 2 (HR = 34.97 [95% CI 2.08-587.73], p = 0.014) and postoperative CRT (HR = 5.55 [95% CI 1.29-23.86], p = 0.021) also predicted worse OS. The 4-year OS among patients with severe lymphopenia was 41% vs. 61% among patients with vs. without severe lymphopenia (log-rank test p = 0.041). Conclusions: Severe lymphopenia significantly correlated with poorer OS in patients with gastric or GEJ cancer treated with CRT. CRT-induced lymphopenia may be an important prognostic factor for survival in this patient population. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating CRT-induced lymphopenia.

scholarly journals CCL2 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Shows Divergent Prognostic Potential for Bladder Cancer Patients Depending on Lymph Node Stage

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1253 ◽  
Author(s):  
Markus Eckstein ◽  
Elena Epple ◽  
Rudolf Jung ◽  
Katrin Weigelt ◽  
Verena Lieb ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Regression Analysis ◽  
Lymph Node ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Immune Cells ◽  
Independent Prognostic Factor ◽  
Rank Test ◽  
Log Rank Test ◽  
Cox's Regression

Bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications, markers for tumor cells and immune cells that are associated with prognosis are still needed. The chemokine CC motif ligand 2 (CCL2) could be such a marker. We analyzed the expression of CCL2 by immunohistochemistry (IHC) in 168 muscle invasive BCa samples using a tissue microarray. Application of a single cut-off for the staining status of tumor cells (TCs; positive vs. negative) and immune cells (ICs; ≤6% of ICs vs. >6% of ICs) revealed 57 cases (33.9%) and 70 cases (41.7%) with CCL2-positive TCs or ICs, respectively. IHC results were correlated with clinicopathological and survival data. Positive CCL2 staining in TCs was associated with shorter overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) (p = 0.004, p = 0.036, and p = 0.047; log rank test) and appeared to be an independent prognostic factor for OS (RR = 1.70; p = 0.007; multivariate Cox’s regression analysis). In contrast, positive CCL2 staining in the ICs was associated with longer OS, DSS, and RFS (p = 0.032, p = 0.001, and p = 0.001; log rank test) and appeared to be an independent prognostic factor for DSS (RR = 1.77; p = 0.031; multivariate Cox’s regression analysis). Most interestingly, after separating the patients according to their lymph node status (N0 vs. N1+2), CCL2 staining in the ICs was differentially associated with prognosis. In the N0 group, CCL2 positivity in the ICs was a positive independent prognostic factor for OS (RR = 1.99; p = 0.014), DSS (RR = 3.17; p = 0.002), and RFS (RR = 3.10; p = 0.002), whereas in the N1+2 group, CCL2 positivity was a negative independent factor for OS (RR = 3.44; p = 0.019)) and RFS (RR = 4.47; p = 0.010; all multivariate Cox’s regression analyses). In summary, CCL2 positivity in TCs is a negative prognostic factor for OS, and CCL2 can mark ICs that are differentially associated with prognosis depending on the nodal stage of BCa patients. Therefore, CCL2 staining of TCs and ICs is suggested as a prognostic biomarker for BCa patients.

Triple negative breast cancer: An institutional review

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22214-e22214
Author(s):  
M. Dioca ◽  
M. Savignano ◽  
L. Gimenez ◽  
L. Marino ◽  
C. Delfino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Menopausal Status ◽  
Stage I ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Increased Risk

e22214 Background: Triple negative breast cancer (BC) is a distinct group of tumors that show common but heterogeneous morphologic, genetic, and immunophenotypic features. Despite differences in the definition and prevalence, it comprises 8% to 20% of all breast cancers and is associated with an aggressive clinical course with significant risk of either local or systemic relapse and subsequent increased risk of death on short term follow up (particularly in the first 5 years).We study the pathological characteristics and the clinical outcome of a cohort of 77 triple negative BC patients (pts) diagnosed at our Institution. Methods: Between January 1999 and September 2008, 77 (stage I to III) triple negative BC pts. were retrospectively analyzed. All pts had their receptor status, Her neu, ck-5, ck-6 and staining for EGFR by the same pathologist. Pathological parameters (Pp) analyzed were: status of axilary lymph nodes (LN), nuclear grade, histologic grade, mitotic index and vascular invasion and the use of antraciclins in the adjuvant setting. Univariate and multivariate analysis (proporcional hazard regression Cox model) for the Pp associated with relapse, and the log rank test to compare two curves of each Pp for disease free survival (DFS), and overall survival (OS) were performed. Results: The median age was 57.8 years (range 30–86 years).The median follow up time was 57.7 months (range, 4- 241). From 77 Pts. analized, 65 (84.4%) were basal-like and 43 (64.6%) of those were GH3. Stage at the time of presentation was: 16 (20,7%) stage I; 40 (51,9%) stage II; 21 (27,7%) stage III. Pre-menopausal status was 29,48% (23 pts.), and 61% (47 pts) were LN negative. Overall, relapse rate was 38.5 % (n= 30), 63 Pts (81.8%) are still alive. Median DFS was not reached. Global DFS and OS were 59% and 79% respectively, and status of LN was the only prognostic factor. LN- vs LN+ DFS (p< 00.02) and OS p (< 0.02).All others Pp analyzed were not statistically significative. Conclusions: Despite previous studies have demonstrated that triple negative is an independent marker of poor prognosis in BC as a whole, in the LN-negative, and LN-positive groups, in this basal like population only positive LN was an independent poor prognostic factor for DFS and OS. No significant financial relationships to disclose.

A pooled analysis of 1,546 patients with AIDS-related lymphoma (ARL): An assessment of prognostic factors by treatment era.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8524-8524
Author(s):  
Stefan K. Barta ◽  
Michael Samuel ◽  
Xiaonan Xue ◽  
Jeanette Y. Lee ◽  
Nicolas Mounier ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Factor ◽  
Prognostic Significance ◽  
Pooled Analysis ◽  
Cd4 Count ◽  
Significant Prognostic Factor ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Time Period ◽  
Increased Risk

8524 Background: Management of ARL evolved in the last 2 decades. We previously reported prognostic factors in a pooled analysis of 1,546 patients with ARL, and here present analysis of these factors over time to determine if their prognostic significance has changed. Methods: Following a systematic review, we assembled individual patient data from 19 prospective phase 2/3 clinical trials (published 1993-2010) for ARL (n=1,546). Factors analyzed include age, sex, histology, CD4 count, prior history of (h/o) AIDS, & age-adjusted (aa) IPI. The endpoint was overall survival (OS) expressed as the hazard ratio (HR) for death. We used separate Cox proportional hazard models adjusted for the other covariates to determine the significance of each variable in the following time periods: pre-cART [combination antiretroviral therapy] (<1996; n=388), early cART (‘96-‘00; n=694), modern cART (‘01-‘04; n=282) & current era (‘05-‘10; n=182). We also combined all enrollments in one Cox model to test for difference in association with OS over enrollment periods. Results: Rituximab use was limited in the early cART (20%) compared with the modern cART (83%) and current (93%) eras. Histology & sex were not significantly associated with OS in any time period. Increasing age was associated with worse OS in the pre-cART (HR 1.02; p<0.01) and current (HR 1.05, p=0.04) eras. A prior h/o AIDS increased risk of death during early cART (HR 1.31, p=0.047) but was not significant after 2000. Meanwhile, baseline CD4 count <50 was a poor prognostic factor during early (HR 1.78, p<0.01) and modern cART (HR 2.76, p=0.001) eras, but not in the current era. The aaIPI predicted worse OS in each time period (pre-cART: HR 1.54, p<0.0001; early cART: HR 1.49, p<0.0001; modern cART: HR 1.52, p<0.01; current era: HR 2.34, p<0.0001). No significant interaction between each prognostic factor with enrollment was found. Conclusions: In this pooled analysis of 1,546 patients with ARL, aaIPI was the only consistently significant prognostic factor and its effect was magnified in the current era. HIV-related factors gained prognostic relevance in the early and modern cART era but may not be as relevant with current treatment strategies.

968 PROGNOSTIC FACTOR OF CIRCULATING TUMOR CELLS IN HIGH RISK NON-MUSCLE INVASIVE BLADDER CANCER

2010 ◽  
Vol 183 (4S) ◽  
Author(s):  
Ettore De Berardinis ◽  
Gian Maria Busetto ◽  
Alessandro Sciarra ◽  
Cristiano Cristini ◽  
Francesco Minisola ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

901 Non-muscle invasive bladder cancer and circulating tumor cells: Individuation and prognostic value

2012 ◽  
Vol 11 (1) ◽  
pp. e901-e901a
Author(s):  
G.M. Busetto ◽  
R. Giovannone ◽  
G. Antonini ◽  
M. Di Placido ◽  
A. Petracca ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prognostic Value ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Primary signet ring cell histology does not portend worse survival for early stage lung cancer following lobectomy

2021 ◽  
pp. 021849232110459
Author(s):  
Terrance Peng ◽  
Anita Yau ◽  
Li Ding ◽  
Elizabeth A. David ◽  
Sean C. Wightman ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Early Stage ◽  
Signet Ring Cell ◽  
Rank Test ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Increased Risk ◽  
Signet Ring ◽  
Ring Cell ◽  
The Impact

Introduction Signet ring cell (SRC) histology is considered a poor prognostic factor in various cancers. However, primary SRC lung adenocarcinoma is rare and poorly understood. Methods The National Cancer Database was queried to identify treatment-naïve patients who received lobectomy for primary SRC or non-SRC pT1-2N0 lung adenocarcinoma <4 cm within four months of diagnosis. SRC lung adenocarcinoma was defined by ICD-O-3 code 8490, while non-SRC lung adenocarcinoma was defined by ICD-O-3 codes 8140, 8141, 8143, 8147, 8255, 8260, 8310, 8481, 8560, and 8570–8574. The Kaplan-Meier curve and log-rank test was used to compare five-year OS between SRC versus non-SRC lung adenocarcinoma cohorts. The impact of SRC histology on risk of death was assessed using the Cox proportional hazards regression model. Results 48,399 patients were included in this study: 62 with primary SRC lung adenocarcinoma and 48,337 with non-SRC lung adenocarcinoma. The mean age of the overall cohort was 67.0 ± 9.6 years. Five-year OS following lobectomy did not differ significantly between SRC lung adenocarcinoma and non-SRC lung adenocarcinoma cohorts (SRC 73.9% vs. non-SRC 69.3%, p = 0.64). SRC histology did not significantly impact risk of death within five years after lobectomy (HR 0.89, p = 0.66). Conclusions Following lobectomy for pT1-2N0 tumors <4 cm, patients with primary SRC lung adenocarcinoma do not experience worse five-year OS or increased risk of death within five years relative to those with non-SRC lung adenocarcinoma. Additional study, including exploration of emerging molecular profiling data, may serve to better define optimal treatment for this histopathologic group of lung adenocarcinomas.

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