Integrin genetic variants and stage-specific tumor recurrence in patients with stage II and III colon cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3604-3604
Author(s):  
Pierre Oliver Bohanes ◽  
Dongyun Yang ◽  
Fotios Loupakis ◽  
Melissa Janae Labonte ◽  
Armin Gerger ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Cancer Biology ◽  
Tumor Recurrence ◽  
Stage Ii ◽  
Stage Iii ◽  
Nucleotide Polymorphisms ◽  
Direct Dna Sequencing ◽  
Cancer Dormancy

3604 Background: Integrins are key elements in cancer biology regulating tumor growth, angiogenesis and lymphangiogenesis through interactions of the tumor cells with the microenvironment. Recent evidence showing that integrins are critical in cancer dormancy suggests that their differential expression or activity may be responsible for tumor recurrence. Moving from the hypothesis that integrins could have different effects in stage II and III colon cancer, we tested as a primary endpoint whether a comprehensive panel of germline single nucleotide polymorphisms (SNPs) in integrin genes could predict stage-specific time to tumor recurrence (TTR) in stage II and III colon cancer patients. Methods: A total of 234 patients, 105 high-risk stage II and 129 stage III, treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. The median follow-up time was 4.4 years. Whole blood samples were analyzed for 22 germline SNPs in integrin genes using PCR-RFLP or direct DNA-sequencing. Results: In the multivariate analysis,stage II colon cancer patients with at least one G allele for ITGB3 rs4642 had higher risk of recurrence (HR=4.027, 95%CI 1.556-10.421, p=0.004). This association was also significant in the combined stage II-III cohort (HR=1.975, HR 95%CI 1.194-3.269, p=0.008). The predominant role of ITGB3 rs4642 in stage II diseases was confirmed using recursive partitioning, showing that ITGB3 rs4642 was the most important factor in stage II diseases. In contrast, in stage III diseases, both ITGB1 rs2298141 (HR=1.909, 95%CI 1.054-3.459, p=0.033) and ITGA4 rs7562325 (HR=0.227, 95%CI 0.064-0.804, p=0.022) were associated with TTR. The latter showed a significant interaction between stages (p=0.048). Conclusions: This study identifies germline polymorphisms in integrin genes as independent stage-specific prognostic markers for stage II and III colon cancer. These data strengthen the role of tumor dormancy in early colon cancer and may help to select subgroups of patients who may benefit from integrin-targeted treatments.

VEGF and VEGF receptor-2 (VEGFR2) gene polymorphisms predict tumor recurrence in stage II and III colon cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4004-4004 ◽  
Author(s):  
G. Lurje ◽  
A. M. Schultheis ◽  
A. E. Hendifar ◽  
S. Ashouri ◽  
W. Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Tumor Recurrence ◽  
Stage Ii ◽  
Stage Iii ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Vegf Receptor ◽  
Stage Iii Colon Cancer ◽  
Increased Risk

4004 Background: Despite recent advances in the treatment of metastatic colorectal cancer, tailoring adjuvant treatment of stage II and III colon cancer patients remains controversial. Identifying a reliable panel of prognostic and predictive markers for tumor recurrence is critical in selecting an individualized and tailored chemotherapy. Tumor angiogenesis plays an important role in tumor development, progression and metastasis. In this retrospective study, we tested whether a specific pattern of 40 functionally significant polymorphisms in 37 genes involved in angiogenesis and tumor microenvironment will predict the risk of tumor recurrence in stage II and III colon cancer patients treated with adjuvant chemotherapy. Methods: Between 1999 and 2006 blood specimens from 140 patients (69 females and 71 males with a median age of 59 years; range=28–86) were obtained at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC). Sixty-three patients had stage II and 77 had stage III colon cancer. The median follow-up was 5.4 years (range=2.0–16.8). 51 of 140 patients (36.4%) developed tumor recurrence with a 5-year probability of 0.28 ± 0.06 for stage II and 0.40 ± 0.06 for stage III colon cancer patients. Genomic DNA was extracted from peripheral blood and genotypes were determined using PCR based RFLP. Results: Polymorphisms in VEGF (C936T; p=0.009, log-rank) and VEGFR2 (+4422 AC- repeat; p=0.04, log-rank and +1416 T/A; p=0.0009, log-rank) were associated with risk of tumor recurrence in stage III colon cancer patients (n=77). VEGFR2 AC-repeat polymorphisms were additionally associated with risk of recurrence in Stage II colon cancer patients (n=63, p=0.02, log-rank). Conclusion: VEGF C936T and VEGFR2 (+4422 AC-repeat and +1416 T/A) polymorphisms may help to identify Stage II and III colon cancer patients who are at increased risk for developing tumor recurrence. Angiogenesis seems to play a crucial role in tumor recurrence, thus targeting VEGF and VEGFR2 may be of clinical benefit for stage II and stage III colon cancer patients. Large prospective trials are needed to validate these preliminary data. No significant financial relationships to disclose.

Novel colon cancer tumor suppressor gene, β-defensin 1, to predict recurrence in patients with stage II and III colon cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3622-3622
Author(s):  
Melissa Janae Labonte ◽  
Pierre Oliver Bohanes ◽  
Dongyun Yang ◽  
Fotios Loupakis ◽  
Peter M.D. Wilson ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Suppressor ◽  
Membrane Permeability ◽  
Suppressor Gene ◽  
Stage Ii ◽  
Stage Iii ◽  
University Of Southern California ◽  
Nucleotide Polymorphisms ◽  
Direct Dna Sequencing ◽  
Cancer Tumor

3622 Background: Human β-defensin 1 (hBD-1) encoded by the DEFB1 gene is an antimicrobial peptide involved in the innate immune response and is expressed in epithelial cells, including the colon. hBD-1 has been shown to have tumor suppressor functions in urothelial cancer models. We tested whether 4 germline single nucleotide polymorphisms (SNPs) in DEFB1 could predict time to tumor recurrence (TTR) in stage II and III colon cancer (CC) patients. We then sought to demonstrate if hBD-1 has tumor suppressor functions in CC models. Methods: A total of 234 patients, 105 stage II and 129 stage III, treated with 5-FU-based chemotherapy at the University of Southern California were included. The median follow-up time was 4.4 yrs. SNPs were analyzed from whole blood samples using direct DNA-sequencing. To gain insight into hBD-1’s function, hBD-1 expression in CC cell lines was determined by qRT-PCR and Western blotting. hBD-1 expression was induced ectopically and CC cells and viability, membrane permeability, cell-cycle and apoptosis analyzed. Results: Stage III patients with rs1800972 DEFB1 -44G containing genotypes had longer TTR than patients with C/C genotype (11.3 mo vs 2.7 mo; p=.008). In contrast in stage II, patients with rs1799946 DEFB1 -52A containing genotypes, had significantly longer TTR than patients with G/G genotype (16.8 mo vs 5.9 mo; p=.017). In the multivariate analysis, both DEFB1 -44C/G and DEFB1 -52G/A SNPs remained significant, respectively in stage III (HR=.419; 95%CI .201-.87; p=.020) and in stage II (HR=.360; 95%CI .152-.853; p=.020). Haplotype of all four SNPs was significantly associated with stage-specific TTR (to be presented at the meeting). In CC cell line models, there was a loss of hBD-1 expression, and induction of hBD-1 expression resulted in a loss of cell viability, membrane permeability and the induction of apoptosis. Conclusions: The results demonstrate for the first time evidence of hBD-1’s potential influence on the microenvironment and its role as a tumor suppressor in CC. Further studies need to be conducted to better understand the role of hBD-1 in CC development and progression and evaluate the potential utility of hBD-1 as a therapeutic strategy.

Use of germ-line variants in the WNT/β-CATENIN pathway to predict tumor recurrence in adjuvant colon cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14034-e14034
Author(s):  
Peter M.D. Wilson ◽  
David Páez ◽  
Armin Gerger ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Tumor Recurrence ◽  
Cox Regression ◽  
Germ Line ◽  
Stage Ii ◽  
Cox Regression Analysis ◽  
Direct Dna Sequencing ◽  
Stage Ii Colon Cancer

e14034 Background: The Wnt/β-catenin signaling plays a central role in the development and progression of most colon cancers. Germline variants in Wnt/β-catenin pathway genes may result in altered gene function and/or activity, thereby causing inter-individual differences in relation to tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of Wnt/β-catenin pathway genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II colon cancer. Methods: A total of 234 patients treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. Whole blood samples were analyzed for putative functional germline polymorphisms in SFRP3, SFRP4, DKK2, DKK3, Axin2, APC, TCF7L2, WNT5B, CXXC4 genes by PCR-RFLP or direct DNA-sequencing. We also included NOTCH2 and GLI1 variants which belong to the Notch and Hedgehog pathways respectively. Results: The minor allele of WNT5B rs2010851 T>G was significantly associated with a shorter TTR (4.9vs10.7 years; HR: 2.48; 95%CI, (0.96, 6.38); p=0.044) in high-risk stage II colon cancer patients. This result remained significant in the multivariate Cox regression analysis. Conclusions: Despite the importance of Wnt/β-catenin pathway in the development of cancer, only the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for colon cancer patients after 5-fluorouracil-based adjuvant therapy.

Abstract CT263: Post-surgical liquid biopsy-guided treatment of stage III and high-risk stage II colon cancer patients: The PEGASUS trial

2020 ◽  
Author(s):  
Elena Elez ◽  
Filippo Pietrantonio ◽  
Andrea Sartore-Bianchi ◽  
Clara Montagut ◽  
Andres Cervantes ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Ii Colon Cancer

scholarly journals The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients

2010 ◽  
Vol 21 (12) ◽  
pp. 2396-2402 ◽  
Author(s):  
A. Fariña-Sarasqueta ◽  
G. van Lijnschoten ◽  
E. Moerland ◽  
G.-J. Creemers ◽  
V.E.P.P. Lemmens ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Braf V600e Mutation ◽  
Independent Prognostic Factor ◽  
Stage Ii ◽  
Braf V600e ◽  
Stage Iii ◽  
Stage Iii Colon Cancer

Adjuvant treatment in extreme elderly patients with colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 784-784
Author(s):  
Marta Llopis Cuquerella ◽  
Maria del Carmen Ors Castaño ◽  
María Ballester Espinosa ◽  
Alejandra Magdaleno Cremades ◽  
Vicente Boix Aracil ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Elderly Patients ◽  
Cancer Patients ◽  
Adjuvant Treatment ◽  
Stage Ii ◽  
Stage Iii ◽  
Complementary Treatment ◽  
Colorectal Cancer Patients

784 Background: Surgical and adjuvant treatment in extreme elderly ( > 80 years) patients with localized colorectal cancer is an unresolved issue. Owing to the lack of available neither clinical practice nor investigational data in this field we present our experience in this scenario. Methods: We retrospectively reviewed data regarding surgical and complementary treatment for colorectal cancer patients aged more than 80 consecutively attended by General Surgery Department in Vega Baja Hospital between 2008 and 2013. Results: A total number of 115 colorectal cancer patients were registered. 95 patients diagnosed of localized disease were selected for analysis. Colon vs rectal cancer ratio was 4:1. Median age was 83.6 years (80-94). Male sex was predominant (60 patients, 63.2%). Emergency surgery was performed in 15 patients (15.8%). Complementary treatment to surgery was advised, according to international guidelines, in 53 patients (55.8%). 10 patients (18.9%) with an advise of adjuvant treatment finally received it. More patients with rectal cancer received recommended treatment (41.7% rectal vs 12.2% colon cancer). Patients with stage III disease were more frequently finally treated according to guidelines (22.2 % stage III vs 11.8% stage II). More patients with stage II rectal cancer were advised and received treatment (recommendation: 66.7% rectal vs 36.1% colon cancer; administration: 25% rectal vs 7.7% colon cancer). Treatment was also more frequently administered to stage III rectal cancer (50% rectal vs 14.3% rectal cancer) (Table). Conclusions: Our experience in localized colorectal cancer in extreme elderly patients ( > 80 years) showed that, although advised according to guidelines, most of them did not receive adjuvant treatment to surgery. Complementary treatment administration was more common in rectal cancer patients and with more advanced disease. [Table: see text]

KRAS Mutation is Associated with Worse Prognosis in Stage III or High-risk Stage II Colon Cancer Patients Treated with Adjuvant FOLFOX

2014 ◽  
Vol 22 (1) ◽  
pp. 187-194 ◽  
Author(s):  
Dae-Won Lee ◽  
Kyung Ju Kim ◽  
Sae-Won Han ◽  
Hyun Jung Lee ◽  
Ye Young Rhee ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Ii Colon Cancer ◽  
Worse Prognosis

Association of HER2 expression with pathologic features and prognosis in stage II and III colon cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3524-3524
Author(s):  
Zehua Wu ◽  
Huabin Hu ◽  
Yanhong Deng
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Protein Expression ◽  
Cancer Patients ◽  
Stage Ii ◽  
Stage Iii ◽  
Prognostic Impact ◽  
Her2 Expression ◽  
Her2 Protein ◽  
Pathologic Features

3524 Background: We examined the frequency, tumor characteristics, and prognostic impact of HER2 protein expression in stage II and III colon cancer after curative resection. Methods: Paraffin-embedded tumors from consecutive primary stage II and III colon cancer patients were analyzed for HER2 protein expression by immunohistochemistry between April, 2013 and May, 2020. HER2 determination of immunohistochemistry scores (0/1+/2+/3+) was according to HERACLES diagnostic criteria. Results: A total of 2088 stage II and III colon cancer patients were included (53.8% stage II, 46.3% stage III). HER2 scored positive (3+) was detected in 48(2.3%) tumors, and was correlated with younger age (P < 0.001), well/moderate differentiation (P = 0.026), proficient mismatch repair (pMMR) (P = 0.045) and KRAS wild-type (P < 0.001). HER2 scored positive (3+) was not significantly associated with disease-free survival (DFS) compared with HER2 scored negative (0/1+), neither in stage III patients (multivariable HR, 0.86; 95CI, 0.38 to 1.94; P = 0.717), nor in stage II patients (multivariable HR, 1.68; 95CI, 0.74 to 3.84; P = 0.218). In a separate analysis involving stage II patients without any high-risk factor (n = 741), those with HER2 scored positive (3+) tumors (n = 16) showed significantly reduced DFS (multivariable HR, 2.91; 95CI, 1.04 to 8.81; P = 0.041) compared with patients with HER2 scored negative (0/1+) tumors, independent of sex, age and MMR status. Conclusions: HER2 scored positive (3+) was independently associated with poor DFS in stage II colon cancer patients without high-risk factors. HER2 expression determination may help to judge the prognosis of those patients and guide adjuvant chemotherapy.

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