BRAF mutation status and its prognostic significance in 79 canine urothelial carcinomas: a retrospective study (2006‐2019)

The cyclooxygenase-2 (COX-2)–prostaglandin E2 (PGE2) pathway has been implicated in carcinogenesis, with BRAF mutation shown to promote PGE2 synthesis. This study was conducted to evaluate COX-2 expression in a large cohort of Middle Eastern papillary thyroid carcinoma (PTC), and further evaluate the prognostic significance of COX-2 expression in strata of BRAF mutation status. BRAF mutation analysis was performed using Sanger sequencing, and COX-2 expression was evaluated immunohistochemically using tissue microarray (TMA). COX-2 overexpression, noted in 43.2% (567/1314) of cases, was significantly associated with poor prognostic markers such as extra-thyroidal extension, lymph-node metastasis, and higher tumor stage. COX-2 was also an independent predictor of poor disease-free survival (DFS). Most notably, the association of COX-2 expression with DFS differed by BRAF mutation status. COX-2 overexpression was associated with poor DFS in BRAF-mutant but not BRAF wild-type PTCs, with a multivariate-adjusted hazard ratio of 2.10 (95% CI = 1.52–2.92; p < 0.0001) for COX-2 overexpressed tumors in BRAF-mutant PTC. In conclusion, the current study shows that COX-2 plays a key role in prognosis of PTC patients, especially in BRAF-mutated tumors. Our data suggest the potential therapeutic role of COX-2 inhibition in patients with BRAF-mutated PTC.

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Prognostic significance of peritoneal cytology in low-risk endometrial cancer: comparison of laparoscopic surgery and laparotomy

International Journal of Clinical Oncology ◽

10.1007/s10147-020-01854-z ◽

2021 ◽

Author(s):

Satoe Fujiwara ◽

Ruri Nishie ◽

Shoko Ueda ◽

Syunsuke Miyamoto ◽

Shinichi Terada ◽

...

Keyword(s):

Endometrial Cancer ◽

Laparoscopic Surgery ◽

Retrospective Study ◽

Prognostic Significance ◽

Low Risk ◽

Peritoneal Cytology ◽

Chi Square ◽

Significant Difference ◽

Chi Square Test ◽

Positive Peritoneal Cytology

Abstract Background There is uncertainty surrounding the prognostic value of peritoneal cytology in low-risk endometrial cancer, especially in laparoscopic surgery. The objective of this retrospective study is to determine the prognostic significance of positive peritoneal cytology among patients with low-risk endometrial cancer and to compare it between laparoscopic surgery and conventional laparotomy. Methods From August 2008 to December 2019, all cases of pathologically confirmed stage IA grade 1 or 2 endometrial cancer were reviewed at Osaka Medical College. Statistical analyses used the Chi-square test and the Kaplan–Meier log rank. Results A total of 478 patients were identified: 438 with negative peritoneal cytology (232 who underwent laparotomy and 206 who undertook laparoscopic surgery) and 40 with positive peritoneal cytology (20 who underwent laparotomy and 20 who received laparoscopic surgery). Survival was significantly worse among patients with positive peritoneal cytology compared to patients with negative peritoneal cytology. However, there was no significant difference among patients with negative or positive peritoneal cytology between laparoscopic surgery and laparotomy. Conclusion This retrospective study suggests that, while peritoneal cytology is an independent risk factor in patients with low-risk endometrial cancer, laparoscopic surgery does not influence the survival outcome when compared to laparotomy.

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752 The impact of grade of differentiation and BRAF mutation status on neoantigen and immune landscape in papillary thyroid cancer

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0752 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A800-A800

Author(s):

Myungwoo Nam ◽

Woojung Yang ◽

Ju Young Lee ◽

Jaeyoun Choi ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Braf Mutation ◽

Cytolytic Activity ◽

Activity Score ◽

Cyt B ◽

Mutation Status ◽

Poorly Differentiated ◽

Immune Traits ◽

Well Differentiated

BackgroundThe use of immune checkpoint inhibitors (ICIs) in cancer treatment has been approved by the FDA, but its application is experimental in the treatment of papillary thyroid cancer (PTC). Induction of immune response via recognition of neoantigens is considered to be the basis for the treatment mechanism of ICIs.1 However, the neoantigen landscape has not been explored in PTC. Our aim is to investigate the immune landscape of PTC in relation to neoantigens, taking into account the BRAF mutation status and grade of differentiation as contributing factors.MethodsBRAF V600E mutation status and thyroid differentiation scores (TDSs) were gathered from the PTC cohort of The Cancer Genome Atlas (TCGA). TDS was derived from the mRNA expression levels of 16 thyroid function genes to quantify the grade of differentiation. Tumors with TDSs in the 1st quartile and 4th quartile were defined as poorly differentiated and well differentiated, respectively. The neoantigen burden for each sample was predicted using CloudNeo pipeline. The infiltration of immune cells was calculated through CIBERSORT.ResultsAmong 400 patients with predicted neoantigen data, 187 (47%) had BRAF mutations. The BRAF mutated tumors showed increased cytolytic activity score (CYT, p=0.001), increased infiltration of regulatory T cells (Treg, p<0.001), and higher PD-L1 expression (p<0.001) compared to BRAF wild-type tumors (figure 1). In regard to grade of differentiation, poorly differentiated tumors showed increased CYT (p=0.002), increased infiltration of Treg (p<0.001), and higher PD-L1 expression (p<0.001) compared to well differentiated tumors (figure 2). However, BRAF mutation status or grade of differentiation did not correlate with the neoantigen burden. Also, the neoantigen burden did not show any correlations with immune landscape features such as infiltration of CD8+ T cells or Treg, CYT, and PD-L1 expression.Abstract 752 Figure 1Immune traits according to BRAF mutation status. (a) Cytolytic activity score(CYT). (b) Infiltration of regulatory T cells(Tregs). (c) PD-L1 expression.Abstract 752 Figure 2Immune traits according to grade of differentiation. (a) Cytolytic activity score(CYT). (b) Infiltration of regulatory T cells(Tregs). (c) PD-L1 expression.ConclusionsIncreased CYT and higher expression of PD-L1 in the BRAF mutated or the poorly differentiated tumors imply the possible role of ICI use in these subgroups of patients. However, the immune response to these subgroups does not seem to be mediated through the increase in neoantigen formation. Further studies are warranted to explore markers for immunotherapy implication.ReferencesSchumacher TN, Schreiber RD, Neoantigens in cancer immunotherapy. Science 2015; 348:69–74.

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137P Epidermal growth factor receptor mutation status and response to tyrosine kinase inhibitors in advanced Chinese female lung squamous cell carcinoma: A retrospective study

Journal of Thoracic Oncology ◽

10.1016/s1556-0864(21)01979-1 ◽

2021 ◽

Vol 16 (4) ◽

pp. S771

Author(s):

Q. Chang ◽

H. Qiang ◽

C. Tianqing

Keyword(s):

Squamous Cell Carcinoma ◽

Epidermal Growth Factor Receptor ◽

Retrospective Study ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Kinase Inhibitors ◽

Growth Factor Receptor ◽

Lung Squamous Cell Carcinoma ◽

Mutation Status ◽

Epidermal Growth

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An Unusual Case of Desmoplastic Melanoma With Monster Cells Imitating an Atypical Fibroxanthoma

International Journal of Surgical Pathology ◽

10.1177/10668969211044758 ◽

2021 ◽

pp. 106689692110447

Author(s):

Juan J. Ríos-Martín ◽

Manuel Pérez-Pérez ◽

Sebastián Umbría-Jiménez ◽

David Moreno-Ramírez ◽

Ana Vallejo-Benítez

Keyword(s):

Cyclin D1 ◽

Copy Number ◽

Poor Prognosis ◽

Unusual Case ◽

Prognostic Significance ◽

Mutation Status ◽

Atypical Fibroxanthoma ◽

Desmoplastic Melanoma ◽

Aggressive Tumor

Numerous cells with very large and irregular nuclei (“monster” cells) have not hitherto been reported in desmoplastic melanoma (DM). Their prognostic significance in melanomas is a matter of debate, although some authors have associated them with more aggressive tumor behavior. We report a mixed DM on the scalp of an 88-year-old woman imitating an atypical fibroxanthoma. Tumor cells stained positive for SOX10, S100, and cyclin D1; BRAF mutation status was negative, and fluorescence in situ hybridization analysis showed copy number gains in 11q13 (cyclin D1) and 6p25 (RREB1), and loss in 6q23 (MYB). Cyclin D1 amplification is associated with poor prognosis in melanoma.

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