Prognostic Significance of Singular RAS Mutations in Cytologically Indeterminate Thyroid Nodules

TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for RAS mutations in a retrospective series of cSCC. The predictive value of p53 expression, RAS mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of RAS mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. RAS mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. RAS mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (p = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that RAS mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients’ risk stratification.

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Preoperative RAS Mutational Analysis Is of Great Value in Predicting Follicular Variant of Papillary Thyroid Carcinoma

BioMed Research International ◽

10.1155/2015/697068 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Tae Sook Hwang ◽

Wook Youn Kim ◽

Hye Seung Han ◽

So Dug Lim ◽

Wan-Seop Kim ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Thyroid Nodules ◽

Mutational Analysis ◽

Braf V600e ◽

Papillary Thyroid ◽

Follicular Variant ◽

Ras Mutation ◽

Ras Mutations ◽

Codon 61

Follicular variant of papillary thyroid carcinoma (FVPTC), particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6%) had a point mutation in one of the BRAF V600E (n=57), BRAF K601E (n=11), or RAS (n=64) genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC.

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Malignancy Risk in RAS-Mutated Cytologically Indeterminate Thyroid Nodules: Real-World Clinical Experience

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1766 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A865-A865

Author(s):

Joseph Lu ◽

Mark Armin Lupo

Keyword(s):

Surgical Resection ◽

Real World ◽

Thyroid Nodules ◽

Standard Procedure ◽

Molecular Testing ◽

Imaging Features ◽

National Guidelines ◽

Ras Mutations ◽

Risk Of Malignancy

Abstract Introduction: Fine needle biopsy (FNB) is the standard procedure for thyroid nodules meeting criteria for biopsy according to current national guidelines (ATA and ACR). However, 15-25% of biopsies are categorized as indeterminate in the Bethesda Categories III (Atypical/FLUS) or IV (Follicular/Hurthle Neoplasm). Molecular testing is a common way to further risk stratify these nodules for surveillance versus surgical resection. BRAF-like mutations have a high probability of malignancy while RAS-like mutations have a variable risk of malignancy. This study examines the performance of RAS mutations in identifying malignancy or NIFTP in a real-world clinical setting. Methods: 2,372 sequential thyroid FNBs were performed in our center from July 2014 to June 2020. Of these, 367 were subjected to molecular testing with either Thyroseq V2 or V3. 55 RAS-mutated BCIII or IV cases were identified and retrospectively evaluated. NIFTP was considered malignant in the calculations. ATA and ACR ultrasound classification as well as Doppler grade of the study nodule were assessed. Results: 8 cases were excluded due to lack of follow-up or incomplete data. 40 underwent surgical resection based on the cytology and molecular results. 7 did not undergo surgery based on patient preference or comorbidities and had clinical follow up with stable ultrasound for at least 6 months. Surgical pathology results: 67.5% benign, 7.5% NIFTP and 25% malignant. All 4 of the Thyroseq “currently negative” RAS nodules were benign. Of the 36 “positive” cases, 6 with additional mutations had a 66.7% ROM and the 30 RAS-only cases had a 30% ROM. Of the 9 RAS-only cases that were not benign, 3 were NIFTP, 5 FVPTC (2 unencapsulated and 3 encapsulated) and 1 was angio-invasive PTC with extensive extrathyroidal extension (this case had high-risk pre-op imaging features). None had lymph node involvement. Higher allelic frequency, abnormal gene expression (GE) and copy number alterations (CNA) all increased the risk of malignancy/NIFTP; ROM was 50% when both GE and CNA were positive. Nodules that were ATA/ACR moderate and high suspicion had an approximately 40% and 67% ROM respectively with ATA and ACR performing similarly. High intra-nodular vascularity conferred a 46% ROM. Conclusions: RAS mutations represent the most frequent abnormality found in oncogene testing however isolated RAS mutations have a low risk of malignancy and when malignant are generally non-aggressive. When both GE and CNA are positive, the risk increases. US features, including Doppler also contribute to risk assessment. Combining all these features is recommended when counseling patients on active surveillance versus surgical resection of RAS-mutated thyroid nodules.

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Prognostic Significance of K-ras Codon 12 Mutations in Patients With Resected Stage I and II Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.2.668 ◽

1999 ◽

Vol 17 (2) ◽

pp. 668-668 ◽

Cited By ~ 135

Author(s):

Stephen L. Graziano ◽

Gary P. Gamble ◽

Nancy B. Newman ◽

Lynn Z. Abbott ◽

Michelle Rooney ◽

...

Keyword(s):

Median Survival ◽

Squamous Cell ◽

Early Stage ◽

Prognostic Significance ◽

Stage I ◽

Stage Ii ◽

Small Cell Lung ◽

Ras Mutations ◽

Significant Difference ◽

Resected Stage

PURPOSE: The aim of this study was to investigate the prognostic importance of codon 12 K-ras mutations in patients with early-stage non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We identified 260 patients with surgically resected stage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year follow-up. We performed polymerase chain reaction analysis of DNA obtained from paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K-ras. RESULTS: K-ras mutations were detected in 35 of 213 assessable specimens (16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%), and two of 20 adenosquamous carcinomas (10%) (P = .001). G to T transversions accounted for 71% of the mutations. There was no statistically significant difference in overall survival for all patients with K-ras mutations (median survival, 39 months) compared with patients without K-ras mutations (median survival, 53 months; P = .33). There was no statistically significant difference in overall or disease-free survival for subgroups with stage I disease, adenocarcinoma, or non–squamous cell carcinoma or for specific amino acid substitutions. The median survival time for stage II patients with K-ras mutations was 13 months, compared with 38 months for patients without K-ras mutations (P = .03). CONCLUSION: Codon 12 K-ras mutations were more common in adenocarcinomas than in squamous cell carcinomas. For the subgroup with stage II NSCLC, there was a statistically significant adverse effect on survival for the presence of K-ras mutations. However, when the entire group was considered, the presence of K-ras mutations was not of prognostic significance in this cohort of patients with resected early-stage NSCLC.

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Prevalence and Clinical Implications of N-RAS Mutations in Childhood AML – A Report From the Children's Oncology Group.

Blood ◽

10.1182/blood.v114.22.3115.3115 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3115-3115

Author(s):

Jason N. Berman ◽

Robert B. Gerbing ◽

Lillian Sung ◽

Kristen Miller ◽

Jessica A. Pollard ◽

...

Keyword(s):

Signal Transduction ◽

High Risk ◽

Prognostic Significance ◽

Low Risk ◽

Signal Transduction Pathways ◽

Free Survival ◽

Ras Mutations ◽

Significant Difference ◽

Pediatric Aml ◽

The Impact

Abstract Abstract 3115 Poster Board III-52 Mutations in the RAS proto-oncogenes are frequent in acute myeloid leukemia (AML) and serve as prototypic Class I lesions, initiating key downstream hyper-proliferative signal transduction pathways. N-RAS mutations (N-RASmut) are common in AML, occurring in 10-20% of adult and pediatric AML patients; however their prognostic significance in both adults and children remains disputed. Due to a frequent association with a normal karyotype, delineating the impact of these mutations on outcome may enable appropriate risk-adapted therapeutic approaches. Here, we report on the incidence and prognostic significance of N-RASmut in a cohort of 825 pediatric AML patients treated on 2 recent co-operative group studies, CCG-2961 and COG AAML03P1. In total, of the 825 children with de novo AML who underwent N-RAS mutational analysis, 86 (10%) were positive. Gender, age, race, presence of hepatosplenomegaly and FAB subtype were comparable between patients with and without N-RASmut. There was no statistically significant difference between those with and without N-RASmut with respect to specific chromosome class. FLT3/Internal tandem duplications (FLT3/ITD) were less common in those with N-RASmut (2% vs. 9%, p=0.03). In contrast, nucleophosmin (NPM) mutations were more common in those with N-RASmut (13% vs. 5%, p=0.02). Overall, N-RASmut showed a significant correlation with low risk AML (CBF, CEBPαa, or NPM, p=0.04) and an inverse relationship with high risk disease (-5/5q- or -7, FLT3/ITD/high allelic ratio, p=0.007). Patients with N-RASmut had similar complete remission (CR) rates following two courses of induction chemotherapy compared with non-mutated patients (79% vs. 79%, p=0.92). Those in CR had a similar relapse rate regardless of the presence of N-RASmut (RR 39% vs. 36%, p=0.97). Five year event free survival (EFS) and overall survival (OS) from study entry were also comparable, however N-RASmut patients demonstrated a marked increase in overall treatment related mortality (TRM) (21% vs. 14%, p=0.03), which was maintained when high and low risk patients were excluded (22% vs. 11%, p=0.05). Evaluation of TRM in CCG-2961 compared with COG AAML03P1 demonstrated that increased TRM in N-RASmut was only seen in patients treated on CCG-2961 and TRM was primarily due to invasive fungal and gram negative infections. Interestingly, for patients treated on CCG-2961, who received interval compressed intensive induction therapy, this increase in TRM correlated with a decrease in both OS and disease free survival from CR. Remission specimens from patients with N-RASmut were negative for the mutation, demonstrating that an increased infectious risk could not be attributed to a host polymorphism. We found N-RASmut did not contribute to increased disease recurrence in pediatric AML. Our findings indicate that N-RAS mutations do not identify a high risk population, however, as such mutations lead to downstream activation of signal transduction pathways, they may identify a target for directed therapy. Disclosures No relevant conflicts of interest to declare.

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Heterogeneity in Positive Predictive Value of RAS Mutations in Cytologically Indeterminate Thyroid Nodules

Thyroid ◽

10.1089/thy.2017.0635 ◽

2018 ◽

Vol 28 (6) ◽

pp. 729-738 ◽

Cited By ~ 13

Author(s):

Fadi Nabhan ◽

Kyle Porter ◽

Mark A. Lupo ◽

Gregory W. Randolph ◽

Kepal N. Patel ◽

...

Keyword(s):

Positive Predictive Value ◽

Predictive Value ◽

Thyroid Nodules ◽

Ras Mutations

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Prognostic Significance of Somatic Mutations in Treatment of AML in Salvage Setting: A Retrospective Analysis

Blood ◽

10.1182/blood.v126.23.1313.1313 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1313-1313

Author(s):

Birendra KC ◽

Hagop M. Kantarjian ◽

Guillermo Garcia-Manero ◽

Naval Daver ◽

Gautam Borthakur ◽

...

Keyword(s):

Complete Remission ◽

Salvage Therapy ◽

Research Funding ◽

Univariate Analysis ◽

Prognostic Significance ◽

Salvage Treatment ◽

Induction Treatment ◽

Ras Mutations ◽

Cebpa Mutations ◽

New Mutations

Abstract Introduction : Acute myeloid leukemia (AML) is a heterogeneous disease with various cytogenetics and molecular abnormalities that lead to different clinical outcomes. The overall prognostic significance of specific mutations at diagnosis has been described. Some are associated with better prognosis (eg, mutations in the myeloid transcription factor gene CEBPA, mutations in the NPM1 gene in the absence of FLT3-ITD, downregulated HOX expression) and some with an adverse prognosis (eg, FLT3-ITD, high expression of the BAALC gene, overexpression of the ETS-related gene ERG, certain mutations in IDH1 and IDH2). However the impact of these mutations in a salvage setting is not well described. Methods: We retrospectively analyzed the patients with AML who received 1st or 2nd salvage treatment (Salvage 1 & Salvage 2) from September 2012 to June of 2015. All patients included in the study had received induction treatment at MD Anderson. The somatic mutations used in the study were obtained at the time of diagnosis. A total of 108 patients with known mutations who eventually received Salvage 1 were included; these also included the 41 patients who later received Salvage 2. Eight mutations (FLT3, CEBPA, IDH1, IDH2, TP53, NPM1, RAS, and JAK2) were evaluated for their correlation with outcome after salvage therapy, specifically event-free survival (EFS) and overall survival (OS) after salvage 1 and salvage 2. Any new evolving mutation after the treatment was also investigated. Results: Out of 108 patients that received salvage 1 treatment, 27% patients had IDH mutations, 19% had TP53 mutations, 16% had RAS mutations, 15% had FLT3-ITD mutations, 11% had NPM1 mutations, 11% had CEBPA mutations and 6% had JAK2 mutations at the time of diagnosis. Median age was 65 years (range: 19-84), median WBC count 5.9 x 109/L (range: 0.8-250), bone marrow blast 45% (range: 0-93) and peripheral blood blast 15.5% (range: 0-96). Cytogenetic abnormalities according to SWOG/ECOG classification were 5% favorable, 50% intermediate, 41% unfavorable and 12 % indeterminate cytogenetics. Forty-two percent of patients were refractory to induction treatment and 58% had achieved complete remission and relapsed after a median of 7 months (range: 1-22). Complete remission and complete remission with incomplete count recovery (CR/CRi) rate after 1st salvage therapy was 30% (95% CI: 21-39%). Median EFS and OS were 2.2 and 5.0 months, respectively. Among 30 pts with repeat molecular analysis prior to salvage 1, some patients developed new mutations, including 4 that acquired FLT3-ITD, and 1 patient each with new TP53, NPM1 and RAS mutations. Using cox univariate analysis stratified by the cytogenetic risk group, CEBPA (HR: 2.3, 95%CI: 1.1-4.7), TP53 (HR: 2.3, 95%CI: 1.1-4.7), JAK2 (HR: 3.3, 95%CI: 1.3-7.9) mutations were significantly associated with shorter OS after start of salvage 1 (Figure 1&2). Patients with CEBPA and/or TP53 and/or JAK2 mutations had a significantly shorter median OS compared to patients without any of these mutations (2.9 vs 7.6 months, respectively). IDH1, IDH2, FLT3-ITD, NPM1 and RAS mutations were not significantly associated with survival outcome. Among these 108 patients, 41 (38%) later received salvage 2 therapy. After Salvage 1 1 of 5 pts assessed developed a new mutation (TP53) prior to salvage 2. Overall remission (CR/CRi) rate was 29% (95%CI: 16-46%) with 2nd salvage therapy. Median OS was 3.5 months and EFS 1.5 months. Using Cox-univariate analysis stratified by the cytogenetic risk, CEBPA mutation (HR: 8.7, 95%CI: 2.3-33.0) and TP53 mutation (HR: 5.9, 95%CI: 1.3-26.2) were significantly associated with shorter OS. Conclusion: This analysis suggests that CEBPA and TP53 mutations are associated with shorter OS in patients receiving 1st or 2nd salvage therapy after failure of induction therapy. The adverse prognostic influence of CEBPA is particularly notable and requires further study. In addition, occasionally new mutations may arise after treatment failure. Mutation profiling at diagnosis as well as prior to each salvage treatment can thus be used for risk stratification of patients undergoing salvage treatment and to consider for targeted drugs to improve the outcome. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Konopleva: Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding. Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Teva: Research Funding; Pfizer: Consultancy, Research Funding; BerGenBio AS: Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.

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The Positive Predictive Value of RAS Mutations in Cytologically Indeterminate Thyroid Nodules Has Considerable Unexplained Variability Across Studies

Clinical Thyroidology ◽

10.1089/ct.2018;30.269-272 ◽

2018 ◽

Vol 30 (6) ◽

pp. 269-272 ◽

Cited By ~ 2

Author(s):

Brian W. Kim

Keyword(s):

Positive Predictive Value ◽

Predictive Value ◽

Thyroid Nodules ◽

Ras Mutations

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Towards a Purely Oncogenetic Risk Classification of Adult T-ALL: a GRAALL Study

Blood ◽

10.1182/blood.v120.21.881.881 ◽

2012 ◽

Vol 120 (21) ◽

pp. 881-881

Author(s):

Amélie Trinquand ◽

Aline Tanguy-Schmidt ◽

Raouf Ben Abdelali ◽

Jérôme Lambert ◽

Etienne Lengliné ◽

...

Keyword(s):

High Risk ◽

Lymphoblastic Leukemia ◽

Prognostic Significance ◽

Good Prognosis ◽

Prognostic Impact ◽

Acute Leukemias ◽

Ras Mutations ◽

Genomic Deletions ◽

High Risk Patients ◽

Risk Patients

Abstract Abstract 881 T-cell acute lymphoblastic leukemia (T-ALL) represents a heterogeneous group of acute leukemias, which account for 25% of adult ALL. The GRAALL group recently reported a significant improvement in the outcome of BCR-ABL negative adult ALL using an intensified treatment protocol and a significantly better outcome in T-ALL harbouring NOTCH1 and/or FBXW7 (N/F) mutations compared to unmutated cases. Despite this, a third of N/F mutated T-ALL patients relapse and the identification of a T-ALL subgroup with very favorable outcome remains desirable. In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and 2005 trials, we searched for N/K-RAS (exon 1) mutations and PTEN (exon 7 mutations and gene deletion by CGH-array SNP-6 Affymetrix®) defects, which are considered as “type B3” mutations involved in pre-TCR signalling. Overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method, and then compared by the log-rank test. NOTCH1 and/or FBXW7 mutations were identified in 143 (67%) of the 212 patients and lack of N/F mutation was associated with a poor prognostic. N-RAS, K-RAS and PTEN mutations were identified in 3/191 (1.6%), 17/191 (8.9%) and 17/175 (9.7%) patients, respectively. PTEN genomic deletions/mutations and N/K-RAS activating mutations were virtually mutually exclusive. N/K-RAS mutations were more frequent in TCR negative phenotype and CNS positive T-ALLs, but did not correlate with other classical parameters, EGIL phenotype, N/F status, or cortico- or chemo-sensitivity. PTEN alterations were more frequent in mature TCR expressing, SIL-TAL+, N/F unmutated cases with high leukemic bulk tumors, but did not significantly differed with respect to age, gender, CNS involvement, cortico- or chemo-sensitivity. When analyzed separately, N/K-RAS mutations or PTEN genomic abnormalities demonstrated trends to a worse outcome. We then analyzed the effect of N/K-RAS mutations and/or PTEN genomic abnormalities on the good prognosis associated with N/F mutations by a multivariate Cox model for EFS and OS, entering the two N/F and RAS/PTEN covariates, as well as an interaction term. The prognostic significance of N/F mutations was still observed (HR, 0.26 [95% CI, 0.15–0.46] and 0.26 [95% CI, 0.14–0.49] with P<0.0001 for EFS and OS, respectively), with a significant interaction between N/F and RAS/PTEN mutations (P=0.03 and 0.05 for EFS and OS, respectively. In other terms, the favorable impact of N/F mutation was still observed in, and was restricted to patients without RAS/PTEN abnormalities. These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation (97 out of 189 [51%] patients in the present cohort) and all other patients (49%, including 13% N/F and RAS/PTEN mutated cases) as high-risk patients (Figures 1A and 1B). Comparing this refined oncogenetic classifier to the simple N/F classification, hazard ratios for high-risk patients increased from 2.6 (95% CI, 1.7–4.0) to 3.25 (95% CI, 2.0–5.3) for EFS and from 2.5 (95% CI, 1.5–4.0) to 3.3 (95% CI, 1.9–5.8) for OS. When adjusting the effect of the new N/F-RAS-PTEN classifier to age (using the 35-year cutoff) and WBC (using the 100.109/L cut-off), the oncogenetic classifier remained the only significant prognostic covariate (HR= 3.2 (95% CI, 1.9–5.15) and 3.2 (95% CI, 1.9–5.6); P<0.0001 and <0.0001, for EFS and OS, respectively). The prognostic impact was maintained when GRAALL-2003 and GRAALL-2005 patients were analysed separately. Taken together, these data demonstrate that detection of RAS and PTEN mutations add significant prognostic value to assessment of N/F status, allowing identification of nearly 50% very good prognosis T-ALL adults. Figure 1A Figure 1A. Figure 1B Figure 1B. Disclosures: No relevant conflicts of interest to declare.

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K-ras Mutations in DNA Extracted From the Plasma of Patients With Pancreatic Carcinoma: Diagnostic Utility and Prognostic Significance

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.2.578 ◽

1999 ◽

Vol 17 (2) ◽

pp. 578-578 ◽

Cited By ~ 146

Author(s):

Antoni Castells ◽

Pere Puig ◽

Josefina Móra ◽

Jaume Boadas ◽

Loreto Boix ◽

...

Keyword(s):

Chronic Pancreatitis ◽

Pancreatic Carcinoma ◽

Prognostic Significance ◽

Ductal Adenocarcinoma ◽

Diagnostic Utility ◽

Plasma Dna ◽

Ras Gene ◽

Mutant Type ◽

Ras Mutations ◽

Type K

PURPOSE: Previous studies have demonstrated the presence of K-ras mutations in the plasma of patients with pancreatic carcinoma. However, the diagnostic utility and the prognostic significance of this finding have never been addressed. PATIENTS AND METHODS: Forty-four consecutive patients with histologically confirmed primary pancreatic ductal adenocarcinoma were included. A control group of 37 patients with chronic pancreatitis, 10 patients with other tumors of the pancreatic area, nine patients with acute pancreatitis, and four healthy volunteers was also included. Plasma DNA was isolated and K-ras codon-12 mutations were analyzed by means of restriction fragment length polymorphism-polymerase chain reaction and single-strand conformation polymorphism techniques. Patients were followed up to establish their clinical outcome. RESULTS: The mutant-type K-ras gene was found in plasma DNA samples of 12 (27%) of 44 patients with pancreatic ductal adenocarcinoma; this finding was related to the tumor stage (P = .05), mainly in the presence of distant metastases (P = .02). In addition, K-ras mutations were detected in the plasma DNA of two (5%) of 37 patients with chronic pancreatitis. In the subset of patients with pancreatic masses, the sensitivity and specificity of plasma K-ras analysis for pancreatic adenocarcinoma were 27% and 100%, respectively. Finally, pancreatic carcinoma patients with the mutant-type K-ras gene in plasma DNA exhibited a shorter survival time than patients with the wild-type gene (P < .005), and plasma K-ras mutations were identified as the only independent prognostic factor (odds ratio, 1.51; 95% confidence interval, 1.02 to 2.23). CONCLUSION: Plasma K-ras analysis is a highly specific, low-sensitivity approach that has diagnostic and prognostic clinical implications in patients with pancreatic carcinoma.

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