scholarly journals Understanding the Pattern of Oropharyngeal Cancers from North-East Romanian Patients

2021 ◽  
Vol 11 (24) ◽  
pp. 12079
Author(s):  
Ramona Gabriela Ursu ◽  
Simona Eliza Giusca ◽  
Irene Alexandra Spiridon ◽  
Bianca Manole ◽  
Mihai Danciu ◽  
...  
Keyword(s):  
Tongue Cancer ◽  
Growth Factor Receptor ◽  
Hpv Dna ◽  
North East ◽  
Formalin Fixed Paraffin ◽  
Screening Strategies ◽  
Formalin Fixed Paraffin Embedded ◽  
Allele Specific ◽  
Hpv18 E6 ◽  
Taqman Pcr

Background: Human papilloma virus (HPV) is acknowledged as a risk factor for oropharyngeal squamous cellular cancers (OPSCC), of which the dominant types are tonsillar (TSCC) and base of tongue cancer (BOTSCC). Objective: To assess the role of HPV in selected OPSCC cases, from Romanian patients by sensitive and complementary molecular assays. Material and Methods: Fifty-four formalin fixed paraffin embedded (FFPE) OPSCC samples were analyzed for HPV DNA by a PCR-based bead-based multiplex-assay. Thirty-four samples were tested for HPV RNA and for overexpression of p16INK4a by immunohistochemistry. Twenty samples were evaluated by Competitive Allele-Specific Taqman PCR (CAST-PCR) for fibroblast growth factor receptor 3 protein (FGFR3) status. Results: A total of 33.3% (18/54) OPSCC samples were positive for HPV DNA. HPV16 was the most frequent type (30%, 16/54); followed by HPV18 (3.7%, 2/54); and 1 sample (1.8%) was positive for both HPV16 and 18. HPV18 E6*I was detected in a HPV18 DNA-positive oropharynx tumor. Four samples positive for HPV16 were also positive for p16INK4a. All the tested samples were negative for FGFR3. Conclusions: The increased HPV16 prevalence is in line with similar studies and is a new confirmation that HPV16 is the most prevalent type in our country; supporting the potential benefit of prophylactic vaccines. Overall, there is no concordance between DNA and any of the two other analytes that are considered being markers of HPV-driven cancers. There is a need to explore novel screening strategies that could be broadly used in the clinical routine to initiate preventive measures.

scholarly journals Incorporation of Cervista Human Papillomavirus 16/18 Assay Into Algorithms for Classifying Human Papillomavirus Status in Formalin-Fixed, Paraffin-Embedded Head and Neck Squamous Carcinoma Specimens

2018 ◽  
Vol 143 (3) ◽  
pp. 356-361
Author(s):  
Ming Guo ◽  
Abha Khanna ◽  
Jianping Wang ◽  
Michelle D. Williams ◽  
Neda Kalhor ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Ffpe Tissue ◽  
Hpv 16 ◽  
Hpv Dna ◽  
Formalin Fixed Paraffin ◽  
Hpv Status ◽  
Formalin Fixed Paraffin Embedded ◽  
Hpv Assays ◽  
Formalin Fixed

Context.— Human papillomavirus (HPV) DNA in situ hybridization (ISH) assay and p16 immunohistochemistry (IHC) are used to determine high-risk HPV status in formalin-fixed, paraffin-embedded (FFPE) tissues in oropharyngeal squamous cell carcinoma (SCC). Although high sensitivity and specificity for HPV can be obtained by combined p16 IHC and HPV DNA ISH, the occasional discrepancy between these assays has prompted evaluation of Cervista HPV assays in FFPE tissue from patients with oropharyngeal SCC. Objective.— To compare the efficacy of Cervista HPV 16/18 and Cervista HPV HR assay to that of HPV DNA ISH assay and p16 IHC in FFPE tissue in head and neck squamous cell carcinoma of oropharyngeal origin. Design.— Archived FFPE tissue from 84 patients with SCC of oropharyngeal origin and available HPV DNA ISH and p16 IHC test results were tested with the Cervista HPV 16/18 assay and further verified by polymerase chain reaction (PCR)–based HPV16/18 genotyping tests in cases with discrepancy. Results.— Of the 84 specimens, 75% (63 of 84) were positive and 16% (13 of 84) had discrepant or equivocal findings by p16 IHC and HPV DNA ISH testing. Use of Cervista HPV assays, either to clarify discrepant/equivocal findings or as confirmation after initial p16 IHC/HPV DNA ISH tests, identified 81% (68 of 84) of HPV-positive cases without equivocal HPV results. Five of 13 cases with discrepancy or equivocal HPV DNA ISH results tested positive for HPV16 or HPV18 by Cervista HPV 16/18 assay, which was further confirmed by PCR-based HPV 16/18 genotyping. Conclusions.— The Cervista HPV assays are a reasonable alternative to HPV DNA ISH in determining HPV status in FFPE tissue specimens from patients with oropharyngeal SCC.

Epidermal growth factor receptor (EGFR) as a predictive and prognostic marker in patients with advanced colorectal cancer (aCRC): The MRC COIN trial experience.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 359-359 ◽  
Author(s):  
R. A. Adams ◽  
M. D. James ◽  
C. G. Smith ◽  
R. H. Wilson ◽  
D. Fisher ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Growth Factor Receptor ◽  
Predictive Marker ◽  
Prognostic Effect ◽  
First Line Therapy ◽  
Formalin Fixed Paraffin ◽  
Trial Experience ◽  
Formalin Fixed Paraffin Embedded ◽  
Epidermal Growth ◽  
License Requirement

359 Background: KRAS mutation has been shown to be a more effective (though negative) biomarker for selection of patients for EGFR targeted therapy in aCRC. However, positive EGFR immunohistochemistry (IHC) remains a license requirement and was an inclusion criterion in most trials to date. The MRC COIN trial recruited 2445 pts into 3 arms of oxaliplatin + fluoropyrimidine +/- cetuximab without prior EGFR assessment. This trial provides a unique opportunity to definitively examine the role of EGFR IHC as prognostic and predictive marker and potentially the evidence required to remove this assessment from the license for this drug. Methods: Formalin-fixed paraffin embedded (FFPE) tissue was stained retrospectively for EGFR using Dako kit in a national reference lab. Results were assessed by 3 reviewers (BJ, SS, RA) using digital imaging software in a blinded fashion, then by BJ/SS providing consensus for discrepancies. EGFR scoring was assessed as a prognostic variable in association with selected patient, tumor and biochemical data. Cut off points examined for +ve vs -ve tumours, in terms of total tumour cells demonstrating membrane staining, were: 0% vs >0%; <10% vs ≥10%; <20% vs ≥20%. Results: EGFR IHC was adequately assessed for 1621 pts (66% of randomised), 22% were negative (0%) and 78% positive (>0%), balanced across arms. EGFR was not prognostic for PFS within KRAS wt pts at the standardized cut off point 0% vs >0% HR=1.11 95% CI 0.91-1.36 p=0.31 but was at <10% vs ≥10% (HR=1.27 95% CI 1.07-1.52 p=0.008) this was robust to other prognostic variables. No effect was seen for overall response or survival. There was no prognostic effect for the KRAS mutant group. In the 1065 assessable pts randomised to +/- cetuximab, no evidence of EGFR IHC as a predictive marker for response or survival outcomes was observed for the addition of cetuximab to chemotherapy (OS HR=1.11 95% CI 0.70-1.75 p=0.66; PFS HR=0.95 95% CI 0.64-1.43 p=0.82). Conclusions: Extensive assessment of samples from this trial suggest a role for EGFR IHC as a prognostic marker in KRAS wt aCRC but refute the predictive value embedded within the licence for cetuximab used in combination with chemo in first-line therapy. [Table: see text]

scholarly journals Human DNA decays faster with time than viral dsDNA: an analysis on HPV16 using pathology archive samples spanning 85 years

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Sara Nicolás-Párraga ◽  
◽  
Montserrat Torres ◽  
Laia Alemany ◽  
Ana Félix ◽  
...  
Keyword(s):  
Invasive Cervical Cancer ◽  
Storage Conditions ◽  
Differential Sensitivity ◽  
Decay Kinetics ◽  
Viral Dna ◽  
Hpv Dna ◽  
Human Dna ◽  
Formalin Fixed Paraffin ◽  
Ffpe Samples ◽  
Formalin Fixed Paraffin Embedded

Abstract Background Quality of the nucleic acids extracted from Formalin Fixed Paraffin Embedded (FFPE) samples largely depends on pre-analytic, fixation and storage conditions. We assessed the differential sensitivity of viral and human double stranded DNA (dsDNA) to degradation with storage time. Methods We randomly selected forty-four HPV16-positive invasive cervical cancer (ICC) FFPE samples collected between 1930 and 1935 and between 2000 and 2004. We evaluated through qPCR the amplification within the same sample of two targets of the HPV16 L1 gene (69 bp, 134 bp) compared with two targets of the human tubulin-β gene (65 bp, 149 bp). Results Both viral and human, short and long targets were amplified from all samples stored for 15 years. In samples archived for 85 years, we observed a significant decrease in the ability to amplify longer targets and this difference was larger in human than in viral DNA: longer fragments were nine times (CI 95% 2.6–35.2) less likely to be recovered from human DNA compared with 1.6 times (CI 95% 1.1–2.2) for viral DNA. Conclusions We conclude that human and viral DNA show a differential decay kinetics in FFPE samples. The faster degradation of human DNA should be considered when assessing viral DNA prevalence in long stored samples, as HPV DNA detection remains a key biomarker of viral-associated transformation.

Detection of HPV-DNA by a PCR-based Method in Formalin-fixed, Paraffin-embedded Tissue From Rare Endocervical Carcinoma Types

2010 ◽  
Vol 18 (1) ◽  
pp. 80-85 ◽  
Author(s):  
Sharon Nofech-Mozes ◽  
Mahmoud M. Khalifa ◽  
Nadia Ismiil ◽  
Valerie Dubé ◽  
Reda S. Saad ◽  
...  
Keyword(s):  
Hpv Dna ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

scholarly journals Anti-tumor efficacy of an MMAE conjugated antibody targeting cell surface TACE/ADAM17-cleaved Amphiregulin in breast cancer

2021 ◽  
Author(s):  
Kristopher A Lofgren ◽  
Sreeja Sreekumar ◽  
E Charles Jenkins ◽  
Kyle J Ernzen ◽  
Paraic A Kenny
Keyword(s):  
Breast Cancer ◽  
Cell Surface ◽  
Transmembrane Protein ◽  
Growth Factor Receptor ◽  
Antibody Drug Conjugate ◽  
Estrogen Receptor Signaling ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Immunocompromised Mice

The Epidermal Growth Factor Receptor ligand, Amphiregulin, is a key proliferative effector of estrogen receptor signaling in breast cancer and also plays a role in other malignancies. Amphiregulin is a single-pass transmembrane protein proteolytically processed by TACE/ADAM17 to release the soluble EGFR ligand, leaving a residual transmembrane stalk that is subsequently internalized. Here, we report the development of an antibody drug conjugate, GMF-1A3-MMAE, targeting an AREG neo-epitope revealed following ADAM17-mediated cleavage. The antibody does not interact with uncleaved Amphiregulin, providing a novel means of targeting cells with high rates of Amphiregulin shedding. Using fluorescent dye conjugation, we demonstrated that the antibody is internalized by cancer cells in a manner dependent on the presence of cell surface cleaved Amphiregulin. Antibodies conjugated with monomethyl auristatin E (MMAE) were cytotoxic in vitro and induced rapid regression of established breast tumor xenografts in immunocompromised mice. We further demonstrate that these antibodies recognize the Amphiregulin neo-epitope in formalin fixed paraffin embedded tumor tissue, suggesting their utility as a companion diagnostic for patient selection.

Quantitative Evaluation of Protein Expression as a Function of Tissue Microarray Core Diameter: Is a Large (1.5 mm) Core Better Than a Small (0.6 mm) Core?

2010 ◽  
Vol 134 (4) ◽  
pp. 613-619
Author(s):  
Valsamo K. Anagnostou ◽  
Frank J. Lowery ◽  
Konstantinos N. Syrigos ◽  
Philip T. Cagle ◽  
David L. Rimm
Keyword(s):  
Growth Factor Receptor ◽  
Tissue Microarrays ◽  
Core Size ◽  
Experimental Conditions ◽  
Core Diameter ◽  
Formalin Fixed Paraffin ◽  
Identical Manner ◽  
Formalin Fixed Paraffin Embedded ◽  
Epidermal Growth ◽  
Tumor Types

Abstract Context.—Tissue microarrays (TMAs) have emerged as a high-throughput technology for protein evaluation in large cohorts. This technique allows maximization of tissue resources by analysis of sections from 0.6-mm to 1.5-mm core “biopsies” of standard formalin-fixed, paraffin-embedded tissue blocks and by the processing of hundreds of cases arrayed on a single recipient block in an identical manner. Objective.—To assess the expression of a series of biomarkers as a function of core size. Although pathologists frequently feel better if larger core sizes are used, there is no evidence in the literature showing that large cores are better (or worse) than small cores for assessment of TMAs. Design.—Estrogen receptor, HER2/neu, epidermal growth factor receptor, STAT3, mTOR, and phospho-p70 S6 kinase were measured by immunofluorescence with automated quantitative analysis. One random 0.6-mm field (one 0.6-mm spot) was compared to 6 to 12 fields per spot, representing 1-mm and 1.5-mm cores, for 3 different tumor types. Results.—We show that measurement of a single random 0.6-mm spot was comparable to analysis of the whole 1-mm or 1.5-mm spot (Pearson R coefficient varying from 0.87–0.98) for all markers tested. Conclusions.—Since TMA technology is now being used in all phases of biomarker development, this work shows that TMAs with 0.6-mm cores are as representative as those with any common larger core size for optimization of standardized experimental conditions. Given that a greater number of 0.6-cores can be arrayed in a single master block, use of this core size allows increased throughput and decreased cost.

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