Clinicopathological and prognostic significance of immunophenotypic characterization of endocervical adenocarcinoma using CLDN18, CDH17, and PAX8 in association with HPV status

2021 ◽  
Author(s):  
Shiho Asaka ◽  
Tomoyuki Nakajima ◽  
Koichi Ida ◽  
Ryoichi Asaka ◽  
Chinatsu Kobayashi ◽  
...  
2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi218-vi218
Author(s):  
Maleeha Qazi ◽  
Sabra Salim ◽  
Kevin R Brown ◽  
Neil Savage ◽  
Nicholas Mickolajewicz ◽  
...  

Abstract Recurrence of solid tumors renders patients vulnerable to a distinctly advanced, highly treatment-refractory disease state that has an increased mutational burden and novel oncogenic drivers not detected at initial diagnosis. Improving outcomes for recurrent cancers requires a better understanding of cancer cell populations that expand from the post-therapy, minimal residual disease (MRD) state. We profiled barcoded tumor cell populations through therapy at tumor initiation/engraftment, MRD and recurrence in our therapy-adapted, patient-derived xenograft models of glioblastoma (GBM). Tumors showed distinct patterns of recurrence in which clonal populations exhibited either a priori, pre-existing fitness, or equipotent fitness acquired through therapy. Characterization of the MRD state by single-cell and bulk RNA sequencing revealed a tumor-intrinsic immunomodulatory signature with strong prognostic significance at the transcriptomic level and in proteomic analysis of cerebrospinal fluid (CSF) collected from GBM patients at all stages of disease. Our results provide insight into the innate and therapy-driven dynamics of human glioblastoma, and the prognostic value of the interrogating of the MRD state in solid cancers.


1995 ◽  
Vol 62 (2) ◽  
pp. 196-208
Author(s):  
A. D'Amico ◽  
V. Ficarra ◽  
F. Mastroeni ◽  
G. Caleffi ◽  
A. Porcaro ◽  
...  

The use of cytogenetics in the characterization of bladder tumours has made it possible to demonstrate that chromosomal alterations are correlated with stage and grade of the tumour and have a predictive value as regards both tumour recurrences and progression. In the last decade the chromosomes involved in the main aberrations have been identified, and a negative prognostic significance has been suggested for some chromosomal aberrations. The knowledge of cytogenetics has been deepened by the sophisticated methods of molecular genetics, that have discovered many oncogenes and suppressor genes probably involved in the development of bladder tumours. The most characteristic molecular alterations of these tumours are losses of genetic information on chromosomes 9, 11 and 17, as a consequence of deletions and/or mutations. Such alterations probably cause the loss and/or the inactivation of suppressor genes (partly hypothetic still) and could represent important predictive factors of tumour progression.


2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Michaël Van Damme ◽  
Emerence Crompot ◽  
Nathalie Meuleman ◽  
Marie Maerevoet ◽  
Philippe Mineur ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6004-6004 ◽  
Author(s):  
D. Rischin ◽  
R. Young ◽  
R. Fisher ◽  
S. Fox ◽  
Q. Le ◽  
...  

6004 Background: Previous studies have reported that in patients with oropharyngeal cancer (OPC) the presence of human papilloma virus (HPV) is associated with an improved prognosis. We sought to determine the prognostic importance of HPV and p16 in patients with OPC treated with concurrent chemoradiation on a large international phase III trial. Methods: Patients with previously untreated Stage III or IV head and neck squamous cell cancer were randomized to receive definitive radiotherapy concurrently with either cisplatin or cisplatin plus tirapazamine. In this substudy, analyses were restricted to patients with OPC who received > 60 Gy and did not have major radiation deviations predicted to impact on tumor control. HPV 16/18 were detected by in situ hybridization and scored as detected or undetected. p16 was detected by immunohistochemistry. Nuclear and cytoplasmic staining intensity of tumor cells was scored as grade 0–3, with grade 2 and 3 called positive. Log rank and Cox regression used for survival analyses. p values were 2-sided . Results: 384 out of 861 patients had OPC and met the eligibility criteria. Slides were available for HPV assay in 195 and for p16 in 186, and for both in 173. 54/195 (28%) were HPV positive, 107/186 (58%) were p16 positive. HPV pos tumors were associated with better 2-year overall survival (OS) (94 v 77%, p = 0.007) and better failure-free survival (FFS) (86 v 75%, p = 0.035) compared to HPV neg tumors. Similarly p16 pos tumors were associated with better 2-year OS (92 v 75%, p = 0.004) and FFS (87 v 72%, p = 0.003) compared to p16 neg . After adjustment for stage, Hb and ECOG PS, HPV pos had better OS than HPV neg (HR 0.29, p = 0.018), and p16 pos had better OS than p16 neg (HR 0.39, p = 0.013). When the HPV and p16 results were combined the relative HRs for OS were: HPVpos/p16pos 0.35 (45 patients, 26% of cases), HPVpos/p16neg 0 (3pts, 2%), HPVneg/p16pos 0.73 (58pts, 33%), HPVneg/p16neg 1.79 (67 pts, 39%). Conclusions: Our results confirm the prognostic significance of tumor HPV status in oropharyngeal cancer treated with chemoradiation, but also show that p16 identifies a larger group with an improved prognosis. The HPV neg/p16 pos population has a better prognosis compared to patients with HPV neg/p16 neg tumors. No significant financial relationships to disclose.


2012 ◽  
Vol 44 (20) ◽  
pp. 992-1002 ◽  
Author(s):  
Brian J. Nieman ◽  
Marissa C. Blank ◽  
Brian B. Roman ◽  
R. Mark Henkelman ◽  
Kathleen J. Millen

The mammalian brain and skull develop concurrently in a coordinated manner, consistently producing a brain and skull that fit tightly together. It is common that abnormalities in one are associated with related abnormalities in the other. However, this is not always the case. A complete characterization of the relationship between brain and skull phenotypes is necessary to understand the mechanisms that cause them to be coordinated or divergent and to provide perspective on the potential diagnostic or prognostic significance of brain and skull phenotypes. We demonstrate the combined use of magnetic resonance imaging and microcomputed tomography for analysis of brain and skull phenotypes in the mouse. Co-registration of brain and skull images allows comparison of the relationship between phenotypes in the brain and those in the skull. We observe a close fit between the brain and skull of two genetic mouse models that both show abnormal brain and skull phenotypes. Application of these three-dimensional image analyses in a broader range of mouse mutants will provide a map of the relationships between brain and skull phenotypes generally and allow characterization of patterns of similarities and differences.


2020 ◽  
Author(s):  
Xiaoyu Wang ◽  
Weichun Tang ◽  
Yilin Lu ◽  
Jun You ◽  
Yun Han ◽  
...  

Abstract AS acts on many tumors and its relationship with CESC needs to be researched. TCGA provided Data. SpliceSeq analyzed Splicing profiles. UpSetR displayed the intersections among AS events. Univariate analysis chose survival-associated AS and SF genes. Functional analysis was operated on Enrichr. STRING evaluated PPI information. MCODE searched clustered sub-networks. LASSO and multivariate analysis constructed prognostic model. Risk analysis of tumor infiltrating immune cells was also conducted. 402 AS-generated genes were found to be associated with CESC prognosis. Functional analysis showed that Golgi to lysosome transport was enriched. PPI suggested that UBA52 was most functional. Dendritic cells activated, Dendritic cells resting, Macrophages M0, Mast cells resting, T cells CD4 memory activated and T cells CD8 were most correlative with riskscore. This study identified SNRPA and CELF2 as two CESC-engaged SFs.


2020 ◽  
Vol 129 (9) ◽  
pp. 863-871
Author(s):  
Mariem Ben Elhadj ◽  
Asma Fourati ◽  
Olfa El Amine ◽  
Aida Goucha ◽  
Ahmed El May ◽  
...  

Objectives: Tobacco and alcohol are the main etiological factors common to laryngeal cancers. However, the Human Papilloma Virus (HPV) constitutes an alternative risk factor according to several studies. In Tunisia, despite the annual increasing incidence of laryngeal squamous cell carcinoma (LSCC), the prevalence and prognostic significance of HPV have never been explored. In this study, we sought to highlight HPV DNA in 70 biopsies of laryngeal cancer, and to analyze the status of HPV infection in association with p53, p16, survivin, and IGF-1R expressions. Methods: HPV high risk (HPV HR) DNA was detected in tumors by in situ hybridization. However, the expression of p53, p16, survivin and IGF-1R were stained by immunohistochemistry test. The correlations of HPV status with clinicopathological parameters, overall survival, disease-free survival and proteins expressions were statistically evaluated. Results: HPV HR DNA was detected in 39 out of 70 (55.71%) laryngeal tumors. HPV+ patients have a better overall survival ( P = .081) and long disease-free-survival ( P = .016) with a low rate of recurrence ( P = .006) than HPV– patients. No significant correlations were found between HPV HR status and clinicopathological parameters (all P > .005). Moreover, HPV+ tumors were not associated with expression of p53, p16 and survivin. However, HPV HR status correlates with weak to moderate IGF-1R expression ( P = .043). Conclusion: The substantial detection of HPV HR in LSCC tumors suggest that this virus plays an important part in laryngeal cancer in Tunisia. It is a good prognostic factor. In addition, HPV infection could act to block the pathway of IGF-1R expression.


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