scholarly journals Immunohistochemical Analysis of BRAF (V600E) Mutation and P16 Expression in Malignant Melanoma in Lagos, Nigeria: A 10-Year Retrospective Study

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
O. Obadofin ◽  
K. Badmos ◽  
N. Orsi ◽  
M. Bipin ◽  
O. Rotimi ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Protein Expression ◽  
Immunohistochemical Analysis ◽  
Braf V600e Mutation ◽  
Breslow Thickness ◽  
University Teaching ◽  
Braf V600e ◽  
Clark Level ◽  
P16 Protein ◽  
P16 Expression

Background. In Blacks, malignant melanoma (MM) is associated with greater morbidity and mortality compared to Caucasians. MMs with BRAF V600E mutation as well as those with loss of p16 protein expression are associated with aggressive behavior and worse prognosis. Objectives. We determined BRAF (V600E) mutation status and loss of p16 expression in MM cases in Lagos, Nigeria, and correlated these with histopathologic parameters and patients’ age. Methods. Forty-five cases of MM received between January 2005 and December 2014 in the Anatomic and Molecular Pathology Department of Lagos University Teaching Hospital were subjected to immunohistochemical studies to determine BRAF V600E mutation and p16 protein expression. These included cutaneous (n=37), musosal (n=3), and ocular MM (n=2) as well as lymph node metastatases (n=3). Results. BRAF (V600E) mutations were detected in 5/45 (11%) while 31/45 (69%) of the cases had loss of p16 expression. No statistically significant association was found between the BRAF (V600E) mutation, loss of p16 expression, and histologic parameters such as histologic variant, Clark level, Breslow thickness, and ulceration. Conclusion. BRAF (V600E) mutation was detected only in a small proportion of cases while loss of p16 expression occurred in most cases which also had high Clark level, high Breslow thickness, and ulceration.

Expression of activation induced deaminase (AID) and BRAF V600E mutation in malignant melanoma

2016 ◽  
Vol 84 (1) ◽  
pp. e80-e81
Author(s):  
Daisuke Omoto ◽  
Emi Mashima ◽  
Yumiko Sakuragi ◽  
Natsuko Saito ◽  
Takashi Yamaguchi ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Activation Induced Deaminase

scholarly journals The BRAF V600E Mutation Detection by quasa Sensitive Real-Time PCR Assay in Northeast Romania Melanoma Patients

2021 ◽  
Vol 11 (20) ◽  
pp. 9511
Author(s):  
Elena Porumb-Andrese ◽  
Ramona Gabriela Ursu ◽  
Iuliu Ivanov ◽  
Irina-Draga Caruntu ◽  
Vlad Porumb ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Target Therapy ◽  
Braf Inhibitor ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Clinical Samples ◽  
Primary Cutaneous Melanoma ◽  
Purification Method ◽  
Detection Of Mutations ◽  
National Reporting System

Background: The prevalence of melanoma in Romanian patients is underestimated. There is a need to identify the BRAF V600E mutation to accurately treat patients with the newest approved BRAF inhibitor therapy. This is a pilot study in which we first aimed to choose the optimal DNA purification method from formalin fixation and paraffin embedding (FFPE) malignant melanoma skin samples to assess the BRAF mutation prevalence and correlate it with clinical pathological parameters. Methods: 30 FFPE samples were purified in parallel with two DNA extraction kits, a manual and a semi-automated kit. The extracted DNA in pure and optimum quantity was tested for the BRAF V600E mutation using the quantitative allele-specific amplification (quasa) method. quasa is a method for the sensitive detection of mutations that may be present in clinical samples at low levels. Results: The BRAF V600E mutation was detected in 60% (18/30) samples in patients with primary cutaneous melanoma of the skin. BRAFV600E mutation was equally distributed by gender and was associated with age >60, nodular melanoma, and trunk localization. Conclusions: The high prevalence of BRAF V600E mutations in our study group raises awareness for improvements to the national reporting system and initiation of the target therapy for patients with malignant melanoma of the skin.

scholarly journals The Hidden Story on Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma – Association with Clinical Outcome and Tumor Phenotypes

2019 ◽  
Author(s):  
Lazaro Hiram Betancourt ◽  
A. Marcell Szasz ◽  
Magdalena Kuras ◽  
Jimmy Rodriguez Murillo ◽  
Yutaka Sugihara ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Protein Expression ◽  
Human Cancer ◽  
Expression Profiles ◽  
Drug Efficacy ◽  
Protein Analysis ◽  
Braf V600e ◽  
Current Recommendation ◽  
Cancer Types ◽  
Protein Expression Profiles

In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas do clearly reveal the existence of inter- and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression for the mutated protein is associated with a more aggressive tumor progression. Our study design that is comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis may enable the eventual delineation of patient responders/non-responders and the subsequent therapy of malignant melanoma.

scholarly journals The Hidden Story of Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma—Association with Clinical Outcome and Tumor Phenotypes

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1981 ◽  
Author(s):  
Lazaro Hiram Betancourt ◽  
A. Marcell Szasz ◽  
Magdalena Kuras ◽  
Jimmy Rodriguez Murillo ◽  
Yutaka Sugihara ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Protein Expression ◽  
Human Cancer ◽  
Expression Profiles ◽  
Drug Efficacy ◽  
Protein Analysis ◽  
Braf V600e ◽  
Current Recommendation ◽  
Cancer Types ◽  
Protein Expression Profiles

In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter- and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma.

Prospective immunohistochemical analysis of BRAF V600E mutation in melanoma

2015 ◽  
Vol 46 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Alexandra Thiel ◽  
Monica Moza ◽  
Soili Kytölä ◽  
Arto Orpana ◽  
Tiina Jahkola ◽  
...  
Keyword(s):  
Immunohistochemical Analysis ◽  
Braf V600e Mutation ◽  
Braf V600e

Loss of p16 in recurrent malignant mixed müllerian tumors of the uterus

2006 ◽  
Vol 16 (3) ◽  
pp. 1354-1357
Author(s):  
B. Robinson-Bennett ◽  
R. Z. Belch ◽  
A. C. Han
Keyword(s):  
Tumor Suppressor ◽  
Protein Expression ◽  
Tumor Suppressor Genes ◽  
Antigen Expression ◽  
Genetic Profile ◽  
P16 Protein ◽  
Recurrent Tumors ◽  
Changes Over Time ◽  
P16 Expression ◽  
Over Time

Uterine malignant mixed müllerian tumors (MMMTs) are rare and highly aggressive malignancies with poor clinical prognoses. We examined for differences in the oncoprotein profiles of primary versus recurrent MMMTs. Five cases of recurrent uterine MMMT were examined by paraffin immunohistochemistry for the expression of p53, p16, P-cadherin, and Cerb-B2. P16, p53, and P-cadherin were each expressed in 100%, 80%, and 60% of the primary cases, respectively. Three cases expressed all three oncoproteins. All five cases were negative for Cerb-B2. No difference in antigen expression was seen in the epithelial versus sarcomatous components. Primary and recurrent tumors were concordant for p53, P-cadherin, and Cerb-B2. However, three cases of recurrent tumors were negative for p16 expression. P53, p16, and P-cadherin are common tumor suppressor genes expressed in uterine MMMT. Interestingly, p16 protein expression was lost in some cases of MMMTs when they recurred. This suggests that the oncoprotein and possibly genetic profile of p16 changes over time. We did not observe any difference in antigen expression between areas of epithelial or sarcomatous differentiation, which would support a single pluripotential malignant clone in the histogenesis of these tumors.

scholarly journals p16 Protein Expression and Human Papillomavirus Status As Prognostic Biomarkers of Nonoropharyngeal Head and Neck Squamous Cell Carcinoma

2014 ◽  
Vol 32 (35) ◽  
pp. 3930-3938 ◽  
Author(s):  
Christine H. Chung ◽  
Qiang Zhang ◽  
Christina S. Kong ◽  
Jonathan Harris ◽  
Elana J. Fertig ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hpv Infection ◽  
P16 Protein ◽  
Hazard Ratios ◽  
Hpv Status ◽  
P16 Expression

Purpose Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx. Patients and Methods p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics. Results p16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 (95% CI, 0.42 to 0.95; P = .03) and 0.56 (95% CI, 0.35 to 0.89; P = .01) for progression-free (PFS) and overall survival (OS), respectively. Comparing OPSCC and non-OPSCC, patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC, but patients with p16-negative OPSCC and non-OPSCC have similar outcomes. Conclusion Similar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC. However, further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.

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