Clinical impact of molecular positive lymph node status in colorectal cancer

Background: Genetic variations, localized in the 3′ untranslated region (UTR) in mitogen-activated protein kinase (MAPK) pathway-related genes, may alter the transcription and impact the pathogenesis of laryngeal squamous cell carcinoma (LSCC). The present study investigated the associations of single-nucleotide polymorphisms (SNP), localized in the 3′UTR) of the KRAS, NRAS, and MAPK1 genes with LSCC risk and clinicopathological features. Methods: Genomic DNA and clinical data were collected from 327 adult men with LSCC. The control group was formed from 333 healthy men. Genotyping of the SNPs was performed using TaqMan SNP genotyping assays. Five KRAS, NRAS, and MAPK1 polymorphisms were analyzed. All studied genotypes were in Hardy–Weinberg equilibrium and had the same allele distribution as the 1000 Genomes project Phase 3 dataset for the European population. Results: Significant associations of the studied SNPs with reduced LSCC risk were observed between NRAS rs14804 major genotype CC. Significant associations of the studied SNPs with clinicopathologic variables were also observed between NRAS rs14804 minor T allele and advanced tumor stage and positive lymph node status. SNP of MAPK1 rs9340 was associated with distant metastasis. Moreover, haplotype analysis of two KRAS SNPs rs712 and rs7973450 revealed that TG haplotype was associated with positive lymph node status in LSCC patients. Conclusions: According to the present study, 3′UTR SNP in the NRAS and MAPK1 genes may contribute to the identifications of patients at higher risk of LSCC lymph node and distant metastasis development.

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Effect of a National Cancer Institute Clinical Alert on breast cancer practice patterns.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.9.1783 ◽

1994 ◽

Vol 12 (9) ◽

pp. 1783-1788 ◽

Cited By ~ 16

Author(s):

T P Johnson ◽

L Ford ◽

R B Warnecke ◽

S G Nayfield ◽

A Kaluzny ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

National Cancer Institute ◽

Early Stage ◽

Primary Diagnosis ◽

Positive Lymph Node ◽

Lymph Node Status ◽

Node Status ◽

Positive Lymph Node Status ◽

Treatment Trends

PURPOSE This study evaluates the effect of the 1988 National Cancer Institute Clinical Alert regarding treatment of early-stage breast cancer on the patterns of treatment provided to patients. PATIENTS AND METHODS Data analyzed were collected from the hospital and outpatient records of 12,534 female patients with a primary diagnosis of breast cancer (stages I and II) initially diagnosed during the years 1983 through 1989. RESULTS Analyses revealed that the proportions of patients with a negative lymph node status diagnosed after the May 1988 Clinical Alert who received adjuvant treatment (tamoxifen and/or multidrug chemotherapy) were significantly greater than predicted from treatment trends established before the Alert's release. Proportions of patients with positive lymph node status receiving adjuvant therapy subsequent to the Alert's release, in contrast, did not fall outside the projected confidence intervals for that group. Additional analyses showed a significant effect of the Clinical Alert among several subgroups of node-negative patients. CONCLUSION Findings suggest that the Clinical Alert mechanism, followed by publication in the peer-reviewed scientific literature, is an effective way to communicate important research findings to practitioners in the community. However, the Alert mechanism is controversial and should be used judiciously to ensure its credibility.

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Expression of immunohistochemical markers in ampullary cancer (AC) and association with behavior.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15184 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15184-e15184

Author(s):

Milton Jose De Barros E. Silva ◽

Adriana Regina G. Ribeiro ◽

Maria D. Begnami ◽

Felipe D'Almeida Costa ◽

Wilson Luiz Costa ◽

...

Keyword(s):

Lymph Node ◽

Adjuvant Therapy ◽

Positive Lymph Node ◽

Lymph Node Status ◽

R0 Resection ◽

Histological Subtypes ◽

Curative Intent ◽

Immunohistochemical Markers ◽

Node Status ◽

Positive Lymph Node Status

e15184 Background: Curiously, the ampulla is formed by the union of two distinct types of mucosa: intestinal (GI) and pancreatobiliary(PB). Based on this fact, ACs could have different biologic behaviors. Methods: Between 1999 and 2012 we performed a retrospective analysis of patients with AC that underwent a pancreaticoduodenectomy (PD) with curative intent in our institution and the expressions of immunohistochemical markers related to GI origin (CK20 and CDX2) and to PB origin: (CK7 and MUC1) and its association with outcomes. Results: Twenty-seven patients underwent (PD), (M:F=15:12), median age was 62 (range33-83), 85.2% had R0 resection, 29.6% had positive lymph-nodes, 44.4% had perineural invasion, 22.2% had vascular invasion, 29.6% had lymphatic invasion, 59.2% had moderately differentiated tumors. AJCC stage pathologic grouping was: I=33.3%, II=37%, III= 29.6%; Median follow-up was 33.8 months. Relapse free survival was 43% in 3 years and overall survival was 53.7% in 5 years. The relapse rate was 59.2% and the majority of these relapses (69%) were distant metastasis without local relapse. Only positive lymph-node status (p=0,004, HR: 5.99) and R1 resection (R1: p=0.015, HR: 8.75) were independent prognostic factors for relapse on multivariate analysis. Among the patients, 21 were evaluated for the expression of immunohistochemical markers. Ten AC were classified into TGI type, 9 into PB type and 2 into unusual. An association between PB type and positive lymph node status (p=0.05) and more advanced stage (p=0.05) was found (Fisher’s exact test). There was no difference in relapse and survival between the histological subtypes, however, more PB patients had received adjuvant therapy. Conclusions: Histological subtypes of AC may have different behavior, but they are frequently neglected during decision of adjuvant therapy.

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Tumor necrosis factor-α is associated with positive lymph node status in patients with recurrence of colorectal cancer—indications for anti-TNF-α agents in cancer treatment

Cellular Oncology ◽

10.1007/s13402-011-0027-7 ◽

2011 ◽

Vol 34 (4) ◽

pp. 315-326 ◽

Cited By ~ 25

Author(s):

M. Grimm ◽

M. Lazariotou ◽

S. Kircher ◽

A. Höfelmayr ◽

C. T. Germer ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Positive Lymph Node ◽

Lymph Node Status ◽

Positive Lymph Node Status ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

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Negative to positive lymph node ratio is a superior predictor than traditional lymph node status in stage III colorectal cancer

Oncotarget ◽

10.18632/oncotarget.10806 ◽

2016 ◽

Vol 7 (44) ◽

pp. 72290-72299

Author(s):

Qingguo Li ◽

Lei Liang ◽

Huixun Jia ◽

Xinxiang Li ◽

Ye Xu ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Ratio ◽

Positive Lymph Node ◽

Stage Iii ◽

Lymph Node Status ◽

Node Status ◽

Node Ratio

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The Prognostic Factor of Lymph Node Status in Colorectal Cancer Patient Received Inadequate Lymph Node Evaluation

Annals of Oncology ◽

10.1093/annonc/mdt203.220 ◽

2013 ◽

Vol 24 ◽

pp. iv98

Author(s):

In Kyu Lee ◽

Hyung Jin Kim ◽

Taek Soo Kwon ◽

Youn Suk Lee ◽

Seong Taek Oh

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Prognostic Factor ◽

Cancer Patient ◽

Colorectal Cancer Patient ◽

Lymph Node Status ◽

Node Status ◽

Lymph Node Evaluation

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Vascular emboli as a prognostic factor in patients with stage III colorectal cancer undergoing radical surgery.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.570 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 570-570

Author(s):

Haiping Pei ◽

Qian Pei ◽

Hong Zhu ◽

Fengbo Tan

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

Lymph Node ◽

Adjuvant Chemotherapy ◽

Radical Surgery ◽

Disease Free Survival ◽

Stage Iii ◽

Lymph Node Status ◽

Node Status ◽

Therapy Strategy

570 Background: The significance of vascular emboli (VE) in stage III colorectal cancer (CRC), the mechanism of their formation and their therapy strategy remain obscure demanding enhanced research. Methods: Data from 323 consecutive patients (192 non-VE, 131 VE) receiving radical surgery and adjuvant chemotherapy in our institution between Jan. 2009 and Nov. 2014 were retrospectively collected. The follow-up deadline was Feb. 2016. Potential prognostic risk factors were tested using univariate and multivariate survival analyses. mRNAs differentially expressed between VE and non-VE stage III CRC were analyzed using Agilent Gene Expression oligo-microarrays (Version 6.5). Patient-derived xenograft (PDX) nude mouse models were constructed to evaluate the efficacy of adjuvant chemotherapy plus targeted drugs (cetuximab or bevacizumab) on VE and non-VE stage III CRC. Results: VE was significantly associated with gross tumor morphology (p = 0.001), histologic type (p < 0.001), lymph node status (p < 0.001), sub-class of stage III (p =0.001), and serum CA199 level (p = 0.022). VE and lymph node status were independent risk factors for overall survival (OS) (p < 0.001, p = 0.008) and disease-free survival (DFS) (p < 0.001, p = 0.007). The median OS and DFS in VE stage III CRC patients were 38 months and 24 months, respectively. Compared with pericarcinous tissue, 809 genes (396 up-, 413 down-regulated) were differently expressed in no-VE tissue, and 1513 genes (898 up-, 615 down-regulated) in VE tissue. The top ten up-regulated protein-coding genes in VE stage III CRC were ITGBL1 (p<0.001), PROCR (p<0.001), CENPW (p<0.001), ZNF485 (p<0.001), VEGFA (p<0.001), DSG3 (p<0.001), CYP24A1 (p=0.001), COL10A1 (p=0.001), HIST3H2A (p=0.001)and PSAT1 (p=0.002). Conclusions: VE appears to be an independent risk factor for the prognosis of stage III CRC patients treated with radical surgery and adjuvant chemotherapy. Differently regulated genes seem to be involved in the formation and progress of VE. The therapy scheme should be more individualized taking into account the VE status.

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