KRAS mutations and relation to prognosis in patients operated for localized pancreatic cancer and other periampullary cancers

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15618-e15618
Author(s):  
N. A. Schultz ◽  
A. Roslind ◽  
I. J. Christensen ◽  
M. Gaustadnes ◽  
J. S. Johansen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Ampullary Cancer ◽  
Duodenal Cancer ◽  
Cancer Tissue ◽  
Kras Mutations ◽  
T Stage ◽  
Kras Status ◽  
Exon 1 ◽  
N Stage ◽  
Cox Analysis

e15618 Background: Prognostic biomarkers in patients with pancreatic cancer might direct patients to optimal treatment. We studied the prognostic value of KRAS mutations in patients operated for pancreatic and other periampullary cancers. Methods: Retrospective study of 328 patients who were operated with a Whipples procedure at a single HBP-center during the period August 1976 to May 2008. For the present pilot study cancer tissue blocks were collected from 58 patients (31 men, 27 women, median age 64, range 33–81 years, ASA 1–3). All had localized pancreatic (n=26), ampullary (n=26) or duodenal cancer (n=6) and were operated during the period June 2001 to May 2008. 32 patients died (3 within the first month after operation and were excluded). Median follow-up time was 41 months (range 7–90). KRAS mutations in exon 1 and 2 were determined by LightScanner analysis (Idaho Technology). Results: KRAS mutations were found in 32 (55%) of the patients; 16 (62%) patients with pancreatic cancer, 13 (50%) with ampullary cancer and in 3 (50%) with duodenal cancer. KRAS status was neither associated with type of cancer (p=0.68), TNM stage (T stage p=0.64, N stage p=0.31). The median survival time for all patients was 22 months (KRAS mutation: 21, 95% CI: 10–40; Wildtype: not reached yet). Univariate Cox analysis showed that T stage (TNM) (1: HR=0.09, 95% CI: 0.02–0.48 p=0.004; 2: HR=0.18, 0.06- 0.51, p=0.0013; 3: HR=0.26, 0.09–0.71, p=0.0089) was a prognostic factor of OS. KRAS status (HR=0.70, 0.33–1.49, p=0.36) and N stage (TNM) (HR=0.53, 0.25–1.11, p=0.09) were not significant factors of OS, but there is a strong tendency for both factors. Conclusions: KRAS mutations are frequent in patients with localized pancreatic, ampullary and duodenal cancers. Preliminary analysis of 58 patients out of our cohort of 328 patients indicate that KRAS mutations may be a marker of overall survival and time to progression. No significant financial relationships to disclose.

scholarly journals No Correlation between KRAS Status and Advanced Pancreatic Adenocarcinoma Survival

2017 ◽  
Vol 6 (2) ◽  
pp. 45 ◽  
Author(s):  
Misato Ogata ◽  
Hironaga Satake ◽  
Takatsugu Ogata ◽  
Yukihiro Imai ◽  
Yukimasa Hatachi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Predictive Biomarker ◽  
First Line ◽  
Kras Mutations ◽  
Kras Status ◽  
The Impact

Erlotinib plus gemcitabine is one of the standard chemotherapies for unresectable pancreatic cancer. Pancreatic cancer has the highest frequency of KRAS gene mutations among human cancers, and some studies suggest that KRAS status might be a predictive biomarker for anti-epidermal growth factor receptor treatment. However, the reliability of this biomarker has not been confirmed. Here, we evaluated the impact of KRAS mutations in pancreatic cancer patients treated with first line gemcitabine-based chemotherapy. 23 patients treated with gemcitabine-based chemotherapy whose KRAS status could be examined from primary or metastatic lesions were enrolled. KRAS mutations were analyzed by sequencing codons 12 and 13. We retrospectively evaluated the correlation between KRAS status, and prognosis and treatment efficacy. Patient characteristics were as follows: median age 68 years, male/female=6/17, PS 0/1=9/14, TNM stage III/IV=1/22, and gemcitabine alone/erlotinib plus gemcitabine=13/10. Among the 23 patients, KRAS codon 12 was mutated in 15, one of whom also had mutation on codon 13. Median progression-free survival (PFS) and overall survival (OS) of all patients were 4.3 months (95% confidence interval (CI): 3.1 to 5.4) and 8.1 months (95% CI: 5.9 to 10.0; events in 96%), respectively. KRAS status showed no association with PFS (p=0.310), OS (p=0.934), or the efficacy of treatment with (p=0.833) or without erlotinib (p=0.478). Thus, in this study, there was no correlation between KRAS status and the efficacy of first line chemotherapy with gemcitabine with or without erlotinib. Identification of a rationale for personalized medicine in pancreatic cancer will require further exploratory prospective studies.

scholarly journals Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue

Pancreatology ◽  
2017 ◽  
Vol 17 (2) ◽  
pp. 285-290 ◽  
Author(s):  
Soichiro Ako ◽  
Kazuhiro Nouso ◽  
Hideaki Kinugasa ◽  
Chihiro Dohi ◽  
Hiroshi Matushita ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Tissue ◽  
Pancreatic Cancer Tissue ◽  
Kras Mutations ◽  
Serum Dna

scholarly journals Neoadjuvant chemotherapy for pancreatic cancer: Effects on cancer tissue and novel perspectives

2017 ◽  
Vol 13 (6) ◽  
pp. 3975-3981 ◽  
Author(s):  
Hidehiro Tajima ◽  
Isamu Makino ◽  
Yoshinao Ohbatake ◽  
Shinichi Nakanuma ◽  
Hironori Hayashi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Tissue

scholarly journals Poly (ADP-Ribose) Polymerase 1 Protein Expression in Normal Pancreas and Pancreatic Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Roberto Castiglione ◽  
Aldo E. Calogero ◽  
Enzo Vicari ◽  
Giovanna Calabrini ◽  
Anna Cosentino ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pancreatic Cancer ◽  
Cell Death ◽  
Pancreatic Adenocarcinoma ◽  
Cancer Tissue ◽  
Normal Pancreas ◽  
Normal Prostate ◽  
Cytoplasmic Staining ◽  
Cancer Of The Pancreas ◽  
Parp 1

Pancreatic cancer is a most frequent cancer in Europe, and the majority of cases of cancer of the pancreas are diagnosed above the age of 65. Radical surgery is the first curative treatment of pancreatic cancer, and alternative or combined therapeutic options, in particular, consist of adjuvant or neoadjuvant chemotherapy, with or without radiotherapy. Many factors, including diet and genetics, have been implicated in the development of cancer of the pancreas. Poly (ADP-ribose) polymerase 1 (PARP-1) protein is required for translocation of the apoptosis-inducing factor (AIF) from the mitochondria to the nucleus. It is involved in programmed cell death processes. Different PARP-1 gene expression proteins have been observed in various tumors such as lung, ovarian, endometrial, skin, and glioblastoma. We evaluated the expression of PARP-1 protein in pancreatic adenocarcinoma and normal pancreas tissues by immunohistochemistry. Protein PARP-1 in the nucleus was found in all samples (normal pancreas and pancreatic adenocarcinoma tissues). No cytoplasmic staining was observed in any sample. PARP-1-positive cells resulted higher in the normal pancreas compared with the pancreas with adenocarcinoma. PARP-1 overexpression in prostate cancer tissue compared with normal prostate suggests a greater activity of PARP-1 in these tumors. These findings suggest that PARP-1 expression in prostate cancer is an attempt to trigger apoptosis in this type of tumor, similarl to that reported in other cancers. This finding suggests that PARP-1-mediated cell death pathways are inhibited in this cancer.

scholarly journals A Circulating Exosome RNA Signature Is a Potential Diagnostic Marker for Pancreatic Cancer, a Systematic Study

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2565
Author(s):  
Yixing Wu ◽  
Hongmei Zeng ◽  
Qing Yu ◽  
Huatian Huang ◽  
Beatrice Fervers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Validation Dataset ◽  
Healthy Controls ◽  
Rna Seq ◽  
Healthy Individuals ◽  
Kras Mutations ◽  
Significant Difference ◽  
Rna Signature

Several exosome proteins, miRNAs and KRAS mutations have been investigated in the hope of carrying out the early detection of pancreatic cancer with high sensitivity and specificity, but they have proven to be insufficient. Exosome RNAs, however, have not been extensively evaluated in the diagnosis of pancreatic cancer. The purpose of this study was to investigate the potential of circulating exosome RNAs in pancreatic cancer detection. By retrieving RNA-seq data from publicly accessed databases, differential expression and random-effects meta-analyses were performed. The results showed that pancreatic cancer had a distinct circulating exosome RNA signature in healthy individuals, and that the top 10 candidate exosome RNAs could distinguish patients from healthy individuals with an area under the curve (AUC) of 1.0. Three (HIST2H2AA3, LUZP6 and HLA-DRA) of the 10 genes in exosomes had similar differential patterns to those in tumor tissues based on RNA-seq data. In the validation dataset, the levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis (AUC = 0.815) and healthy controls (AUC = 0.8558), whereas a slight difference existed between chronic pancreatitis and healthy controls (AUC = 0.586). Of the three genes, the level of HIST2H2AA3 was positively associated with KRAS status. However, there was no significant difference in the levels of the three genes across the disease stages (stages I–IV). These findings indicate that circulating exosome RNAs have a potential early detection value in pancreatic cancer, and that a distinct exosome RNA signature exists in distinguishing pancreatic cancer from healthy individuals.

scholarly journals Impact of KRAS Mutations on Clinical Outcomes in Pancreatic Cancer Patients Treated with First-line Gemcitabine-Based Chemotherapy

2011 ◽  
Vol 10 (10) ◽  
pp. 1993-1999 ◽  
Author(s):  
Seung Tae Kim ◽  
Do Hyoung Lim ◽  
Kee-Taek Jang ◽  
Taekyu Lim ◽  
Jeeyun Lee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
First Line ◽  
Kras Mutations

scholarly journals Detection of KRAS Mutations in Circulating Tumor DNA by Digital PCR in Early Stages of Pancreatic Cancer

2016 ◽  
Vol 62 (11) ◽  
pp. 1482-1491 ◽  
Author(s):  
Nora Brychta ◽  
Thomas Krahn ◽  
Oliver von Ahsen
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Surgical Removal ◽  
Plasma Samples ◽  
Kras Mutations ◽  
Detection Rates ◽  
Early Stages ◽  
Tumor Dna

Abstract BACKGROUND Since surgical removal remains the only cure for pancreatic cancer, early detection is of utmost importance. Circulating biomarkers have potential as diagnostic tool for pancreatic cancer, which typically causes clinical symptoms only in advanced stage. Because of their high prevalence in pancreatic cancer, KRAS proto-oncogene, GTPase [KRAS (previous name: Kirsten rat sarcoma viral oncogene homolog)] mutations may be used to identify tumor-derived circulating plasma DNA. Here we tested the diagnostic sensitivity of chip based digital PCR for the detection of KRAS mutations in circulating tumor DNA (ctDNA) in early stage pancreatic cancer. METHODS We analyzed matched plasma (2 mL) and tumor samples from 50 patients with pancreatic cancer. Early stages (I and II) were predominant (41/50) in this cohort. DNA was extracted from tumor and plasma samples and tested for the common codon 12 mutations G12D, G12V, and G12C by chip-based digital PCR. RESULTS We identified KRAS mutations in 72% of the tumors. 44% of the tumors were positive for G12D, 20% for G12V, and 10% for G12C. One tumor was positive for G12D and G12V. Analysis of the mutations in matched plasma samples revealed detection rates of 36% for G12D, 50% for G12V, and 0% for G12C. The detection appeared to be correlated with total number of tumor cells in the primary tumor. No KRAS mutations were detected in 20 samples of healthy control plasma. CONCLUSIONS Our results support further evaluation of tumor specific mutations as early diagnostic biomarkers using plasma samples as liquid biopsy.

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