Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations

659 Background: BRAF non-V600 mutations occur in 2-3% of colorectal cancer. These mutants can be classified as RAS independent (class 2) or RAS dependent (class 3). We reported BRAF non-V600 mutations could be a negative predictive factor for anti-EGFR therapy in patients (pts) with pretreated metastatic colorectal cancer (mCRC), while mCRC pts with class 3 BRAF mutations could respond to anti-EGFR therapy because of its dependency on receptors and RAS. Methods: This study evaluates the efficacy to anti-EGFR therapy in a large cohort of pts with BRAF non-V600 mutated mCRC. Pts with mCRC referred to the participating centers from 2010 to 2017 were included. Clinicopathological features, efficacy of anti-EGFR therapy, and survival outcomes were stratified by BRAF mutational class. Results: One hundred seventeen pts with BRAF non-V600 mutated mCRC were identified. Median age was 58 years (range, 27-83), 68 pts (58%) were male, and 38 pts (33%) had right-sided tumors. Mucinous histology was seen in 11 cases (9%); concurrent RAS mutations occurred in 31 cases (27%), and 3 cases (3%) were MSI-H. Also, TP53 mutations were detected in 74 pts among 90 analyzed cases (82%). Regarding BRAF mutation subtype, 25/63/29 pts were classified as class 2/3/not reported (NR), respectively. Median OS in RAS wild-type/mutant were 44.8/34.6 months, respectively (p=0.082). The median OS in RAS wild-type pts with BRAF non-V600 mutations for class 2, 3, and NR were 25.7, 44.2, and 79.1 months, respectively (class 2 vs. 3, p=0.219). Among 40 pts treated with anti-EGFR therapy, response rates were 14%, 44%, and 40% for class 2, 3, and NR, respectively. Median PFS was 4.4, 8.3, 4.0 months for class 2, 3, and NR, respectively. Moreover, in 25 pts receiving anti-EGFR therapy as third or later line, response rate was 0%, 27%, and 50% in class 2, 3, and NR, and median PFS was 2.8, 3.7, and 4.0 months (p=0.762), respectively. Conclusions: Pts with class 2 BRAF mutations tend to have a poor prognosis compared to those with class 3 mutations. While almost half of pts with class 3 BRAF mutations responded to anti-EGFR therapy, response was rare for pts with class 2 BRAF mutations, and none achieved objective response in the third or later line.

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Tumor Expression of the Carcinoembryonic Antigen Correlates with High Mitotic Activity and Cell Pleomorphism Index in Lung Carcinoma

Journal of Histology ◽

10.1155/2013/827089 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Rancés Blanco ◽

Charles E. Rengifo ◽

Mercedes Cedeño ◽

Milagros Frómeta ◽

Enrique Rengifo ◽

...

Keyword(s):

Carcinoembryonic Antigen ◽

Mitotic Activity ◽

Carbohydrate Chain ◽

Tumor Biology ◽

Tissue Expression ◽

Clinicopathological Features ◽

Lung Carcinomas ◽

Lung Cancer Patients ◽

Cell Proliferation Inhibition ◽

Tumor Expression

At present, some research efforts are focusing on the evaluation of a variety of tumor associated antigens (TAAs) for a better understanding of tumor biology and genetics of lung tumors. For this reason, we evaluated the tissue expression of carcinoembryonic antigen (CEA) and ior C2 (a cell surface O-linked glycoprotein carbohydrate chain TAA) in lung carcinomas, as well as its correlation with a variety of clinicopathological features. The tissue expression of CEA was evidenced in 22/43 (51.16%) lung carcinomas and it was correlated with mitotic activity, cell pleomorphism indexes, and age of patients. The expression of ior C2 was observed in 15/43 (34.88%) tumors but no correlation with the clinicopathological features mentioned above was obtained. No correlation between both CEA and ior C2 antigens expression and the overall survival (OS) of non-small-cell lung cancer patients was also observed. However, CEA-negative patients displayed higher OS rates as compared with positive ones (69.74 versus 58.26 months). Our results seem to be in agreement with the role of CEA expression in tumor cell proliferation, inhibition of cell polarizations and tissue architecture distortion. The significance of ior C2 antigen in these malignancies and it potential use in diagnosis, prognosis, and/or immunotherapy must be reevaluated.

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Expression of miRNAs in non-small-cell lung carcinomas and their association with clinicopathological features

Tumor Biology ◽

10.1007/s13277-014-2755-6 ◽

2014 ◽

Vol 36 (3) ◽

pp. 1603-1612 ◽

Cited By ~ 18

Author(s):

Elham Tafsiri ◽

Mojtaba Darbouy ◽

Mohammad B. Shadmehr ◽

Anna Zagryazhskaya ◽

Javad Alizadeh ◽

...

Keyword(s):

Small Cell ◽

Clinicopathological Features ◽

Small Cell Lung ◽

Lung Carcinomas

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Evaluation of BRAF mutation as a powerful prognostic factor in advanced and recurrent colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.413 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 413-413

Author(s):

T. Yokota ◽

T. Ura ◽

N. Shibata ◽

D. Takahari ◽

K. Shitara ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Braf Mutation ◽

Kras Mutation ◽

Clinicopathological Features ◽

Wild Type ◽

Braf Mutations ◽

Kras Mutations ◽

Braf Mutant

413 Background: Alterations in the RAS/RAF/ERK signaling pathways frequently occur in colorectal cancer (CRC). KRAS mutations preclude responsiveness to EGFR-targeted therapies for CRC patients. However, prognostic significance of KRAS mutation is still controversial. The aim of this study is to investigate clinicopathological features of KRAS mutation in codon 12 and 13 as well as of BRAF mutation, and to validate prognostic impact of KRAS/BRAF mutation in advanced and recurrent CRC. Methods: The population consisted of 230 unselected patients who had undergone first-line chemotherapy for advanced and recurrent CRC between November 2002 and June 2010. Cycleave PCR was performed to detect a point mutation at codon 12, 13 or 61 in KRAS, and the V600E mutation in BRAF. Prognostic factors associated with survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. Results: KRAS mutations were present in 34.8% (n= 80) of patients, including 23.5% (n = 54) in codon 12, 11.3% (n = 26) in codon 13, and 0% in codon 61. 6.5% (n = 15) of patients had BRAF mutation. None of the CRC patients carried both KRAS and BRAF mutations. The primary tumor lesions were located on the right side of the colon in 60% of the BRAF mutant patients (p=0.0371). Furthermore, BRAF mutant was significantly associated with the pathological subtypes of poorly differentiated adenocarcinoma/mucinous carcinoma (p<0.0001) and peritoneal metastasis (p=0.0059). The median overall survival for BRAF mutant and KRAS 13 mutant patients was 11.0 and 27.7 months, respectively, which was significantly worse than that for KRAS wild-type (wt)/BRAF wt (40.6 months) (BRAF; HR=3.89, 95% CI 1.83-8.24, p<0.001, KRAS13; HR=2.03, 95% CI 1.10-3.74, p=0.024). After adjustment for significant features by multivariate Cox regression analysis, BRAF mutation was associated with poor overall survival (HR, 3.70, 95% CI, 1.48-9.28; p=0.005), together with performance status 2. Conclusions: This retrospective analysis shows that clinicopathological features of CRC patients with BRAF mutations seem to be distinct from those with wild type BRAF. BRAF mutation is one of the most powerful prognostic factors in advanced and recurrent CRC. No significant financial relationships to disclose.

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Aggressiveness of care and overall survival in young metastatic colorectal cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3563 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3563-3563 ◽

Cited By ~ 1

Author(s):

Madeleine Fish ◽

Katie Kanter ◽

Gianluca Mauri ◽

Nora Horick ◽

Jill N Allen ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Massachusetts General Hospital ◽

Performance Status ◽

Clinicopathological Features ◽

Rank Test ◽

Braf Mutations ◽

Younger Patients ◽

Age Related ◽

Mutational Status

3563 Background: Colorectal cancer (CRC) incidence in patients younger than 50 years of age is steadily rising by 2% annually. Early-onset CRC usually presents with more aggressive features; however, data on prognosis are widely conflicting. Clinicians may hold an age-related bias in treating younger patients, but this proclivity and its effects have not been quantified. Methods: Patients with a history of metastatic CRC who consented to a departmental chart review protocol were collected between 2014 and 2018 at Massachusetts General Hospital. The cohort was divided into two groups based on age at initial diagnosis: < 50 and ≥50. Data were gathered on treatments and clinicopathological features. A log-rank test compared survival from the diagnosis of metastatic disease between age groups. The distributions of clinicopathological features were compared using Wilcoxon rank sum tests. Results: 464 metastatic CRC patients were identified. 155 patients (33%) were < 50 (median age 43, 49% female) and 309 patients (67%) were ≥50 (median age 61, 45% female). Sex did not significantly differ between the two groups (p = 0.45). Patients < 50 received more lines of therapy after metastatic diagnosis than patients ≥50 (mean 2.7 v. 2.2; p = 0.002). Younger patients also received more resections of distant metastases (mean 0.62 v. 0.48; p = 0.01). A higher rate of enrollment in clinical trials for patients < 50 approached significance (p = 0.06). Even so, patients < 50 did not see a significant survival benefit over older patients (2/5-year survival from metastatic diagnosis 77%/47% v. 73%/38%, p = 0.23). Patients < 50 had a lower proportion of right-sided tumors (p = 0.0002) and BRAF mutations (p = 0.0009). There was no difference in MSI status (p = 0.28), RAS mutational status (p = 0.40), mucinous features (p = 0.53), or signet ring features (p = 0.26). Conclusions: Overall survival in patients < 50 is similar to patients ≥50, despite patients < 50 receiving more aggressive therapy. Further study is warranted to better understand these differences. Potential areas of interest include performance status, age-related treatment bias, and biological factors.

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Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients

Journal of Korean Medical Science ◽

10.3346/jkms.2014.29.8.1054 ◽

2014 ◽

Vol 29 (8) ◽

pp. 1054 ◽

Cited By ~ 19

Author(s):

Uiju Cho ◽

Woo Jin Oh ◽

Ja Seong Bae ◽

Sohee Lee ◽

Young Sub Lee ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Patients ◽

Clinicopathological Features ◽

Braf Mutations

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Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report

PLoS ONE ◽

10.1371/journal.pone.0248522 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0248522

Author(s):

Fatima El agy ◽

Sanae el Bardai ◽

Ihsane El Otmani ◽

Zineb Benbrahim ◽

Ibn Majdoub Hassani Karim ◽

...

Keyword(s):

Lymph Node ◽

Lymph Nodes ◽

Clinicopathological Features ◽

Wild Type ◽

Braf Mutations ◽

Poor Overall Survival ◽

Exon 2 ◽

Colon Cancers ◽

Kras Codon ◽

Kras Exon

This study aimed to estimate the incidence of KRAS, NRAS, and BRAF mutations in the Moroccan population, and investigate the associations of KRAS and NRAS gene mutations with clinicopathological characteristics and their prognosis value. To achieve these objectives, we reviewed medical and pathology reports for 210 patients. RAS testing was investigated by Sanger sequencing and Pyrosequencing technology. BRAF (exon 15) status was analyzed by the Sanger method. The expression of MMR proteins was evaluated by Immunohistochemistry. KRAS and NRAS mutations were found in 36.7% and 2.9% of 210 patients, respectively. KRAS exon 2 mutations were identified in 76.5% of the cases. RAS-mutated colon cancers were significantly associated with female gender, presence of vascular invasion, classical adenocarcinoma, moderately differentiated tumors, advanced TNM stage III-IV, left colon site, higher incidence of distant metastases at the time of diagnostic, microsatellite stable phenotype, lower number of total lymph nodes, and higher means of positive lymph nodes and lymph node ratio. KRAS exon 2-mutated colon cancers, compared with KRAS wild-type colon cancers were associated with the same clinicopathological features of RAS-mutated colon cancers. NRAS-mutated patients were associated with lower total lymph node rate and the presence of positive lymph node. Rare RAS-mutated tumors, compared with wild-type tumors were more frequently moderately differentiated and associated with lower lymph node rate. We found that KRAS codon 13-mutated, tumors compared to codon 12-mutated tumors were significantly correlated with a higher death cases number, a lower rate of positive lymph, lower follow-up time, and poor overall survival. Our findings show that KRAS and NRAS mutations have distinct clinicopathological features. KRAS codon 13-mutated status was the worst predictor of prognosis at all stages in our population.

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