scholarly journals Unclassified mesenchymal sarcoma with NTRK1-KHDRBS1 gene fusion: a case report of long-term tumor-free survival with crizotinib treatment

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weijie Chen ◽  
Huimei Wang ◽  
Dongxian Jiang ◽  
Lijuan Luan ◽  
Yuhong Zhou ◽  
...  
Keyword(s):  
Gene Fusion ◽  
Immunohistochemical Analysis ◽  
Genetic Alterations ◽  
Detection Methods ◽  
Gene Fusions ◽  
Term Survival ◽  
Pseudomyogenic Hemangioendothelioma ◽  
Dendritic Cell Sarcoma ◽  
Trk Inhibitors

Abstract Background Mesenchymal sarcomas are tumors that originate from mesenchymal tissue. Most mesenchymal sarcomas can be accurately classified, but some are unclassifiable in clinical practice. Molecular detection methods enable patients to benefit from molecular-targeted therapies for many cancers, including lung, breast, and bowel cancers. Further, even unclassified tumors can have therapeutic targets. NTRK gene fusions are sporadic genetic alterations that occur across tumor entities. If NTRK gene fusions are detected, TRK inhibitors can be used regardless of the tumor entity. Case presentation This report describes a case with an unclassifiable mesenchymal sarcoma carrying a neurotrophic tyrosine receptor kinase NTRK1-KHDRBS1 gene fusion that was diagnosed and treated at multiple hospitals. Diagnostic work-up included pathological and immunohistochemical analysis, which excluded angiosarcoma, dendritic cell sarcoma, and pseudomyogenic hemangioendothelioma. The patient achieved a long-term survival without tumor relapse after treatment with crizotinib. Conclusions This case will be of significant interest to pathologists because, despite the tumor being unclassified, a molecular target was identified. Although the FDA does not currently approve crizotinib for treatment of patients harboring NTRK gene fusions, this case provides new insights for diagnosis and treatment of mesenchymal sarcomas with NTRK1 gene translocations. Similar to ALKomas, which can be successfully treated using NTRK molecular-targeted therapy, tumors with NTRK gene translocations can be classified as NTRKomas, even when they occur at different organ sites, and with varying histological morphologies, and immunophenotypes.

scholarly journals Genetic Alterations in Patients With Esophageal Cancer With Short- and Long-Term Survival Rates After Curative Esophagectomy

1997 ◽  
Vol 226 (2) ◽  
pp. 162-168 ◽  
Author(s):  
Yutaka Shimada ◽  
Masayuki Imamura ◽  
Ichio Shibagaki ◽  
Hisashi Tanaka ◽  
Tokiharu Miyahara ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Survival Rates ◽  
Genetic Alterations ◽  
Term Survival ◽  
Long Term Survival ◽  
Short And Long Term ◽  
Curative Esophagectomy

scholarly journals Anaerobic Survival of Pseudomonas aeruginosa by Pyruvate Fermentation Requires an Usp-Type Stress Protein

2006 ◽  
Vol 188 (2) ◽  
pp. 659-668 ◽  
Author(s):  
Kerstin Schreiber ◽  
Nelli Boes ◽  
Martin Eschbach ◽  
Lothar Jaensch ◽  
Juergen Wehland ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Stationary Phase ◽  
Gene Fusion ◽  
Laser Scanning Microscopy ◽  
Green Fluorescent Protein Gene ◽  
Confocal Laser ◽  
Term Survival ◽  
Long Term Survival ◽  
Pyruvate Fermentation

ABSTRACT Recently, we identified a pyruvate fermentation pathway in Pseudomonas aeruginosa sustaining anaerobic survival in the absence of alternative anaerobic respiratory and fermentative energy generation systems (M. Eschbach, K. Schreiber, K. Trunk, J. Buer, D. Jahn, and M. Schobert, J. Bacteriol. 186:4596-4604, 2004). Anaerobic long-term survival of P. aeruginosa might be essential for survival in deeper layers of a biofilm and the persistent infection of anaerobic mucus plaques in the cystic fibrosis lung. Proteome analysis of P. aeruginosa cells during a 7-day period of pyruvate fermentation revealed the induced synthesis of three enzymes involved in arginine fermentation, ArcA, ArcB, and ArcC, and the outer membrane protein OprL. Moreover, formation of two proteins of unknown function, PA3309 and PA4352, increased by factors of 72- and 22-fold, respectively. Both belong to the group of universal stress proteins (Usp). Long-term survival of a PA3309 knockout mutant by pyruvate fermentation was found drastically reduced. The oxygen-sensing regulator Anr controls expression of the P PA3309-lacZ reporter gene fusion after a shift to anaerobic conditions and further pyruvate fermentation. PA3309 expression was also found induced during the anaerobic and aerobic stationary phases. This aerobic stationary-phase induction is independent of the regulatory proteins Anr, RpoS, RelA, GacA, RhlR, and LasR, indicating a currently unknown mechanism of stationary-phase-dependent gene activation. PA3309 promoter activity was detected in the deeper layers of a P. aeruginosa biofilm using a P PA3309-gfp (green fluorescent protein gene) fusion and confocal laser-scanning microscopy. This is the first description of an Anr-dependent, anaerobically induced, and functional Usp-like protein in bacteria.

scholarly journals Long Term Survival in Patients Suffering from Glio-blastoma Multiforme: A Single-Center Observational Cohort Study

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 209 ◽  
Author(s):  
Daniele Armocida ◽  
Alessandro Pesce ◽  
Federico Di Giammarco ◽  
Alessandro Frati ◽  
Antonio Santoro ◽  
...  
Keyword(s):  
Overall Survival ◽  
Genetic Alterations ◽  
Survival Advantage ◽  
Motor Disorder ◽  
Term Survival ◽  
Surgery Patient ◽  
Dismal Prognosis ◽  
Idh Mutations ◽  
Long Term Survivors

Background: Glioblastomas (GBM) are generally burdened, to date, by a dismal prognosis, although long term survivors have a relatively significant incidence. Our specific aim was to determine the exact impact of many surgery-, patient- and tumor-related variables on survival parameters. Methods: The surgical, radiological and clinical outcomes of patients have been retrospectively reviewed for the present study. All the patients have been operated on in our institution and classified according their overall survival in long term survivors (LTS) and short term survivors (STS). A thorough review of our surgical series was conducted to compare the oncologic results of the patients in regard to: (1) surgical-(2) molecular and (3) treatment-related features. Results: A total of 177 patients were included in the final cohort. Extensive statistical analysis by means of univariate, multivariate and survival analyses disclosed a survival advantage for patients presenting a younger age, a smaller lesion and a better functional status at presentation. From the histochemical point of view, Ki67 (%) was the strongest predictor of better oncologic outcomes. A stepwise analysis of variance outlines the existence of eight prognostic subgroups according to the molecular patterns of Ki67 overexpression and epidermal growth factor receptor (EGFR), p53 and isocitrate dehydrogenase (IDH) mutations. Conclusions: On the grounds of our statistical analyses we can affirm that the following factors were significant predictors of survival advantage: Karnofsky performance status (KPS), age, volume of the lesion, motor disorder at presentation and/or a Ki67 overexpression. In our experience, LTS is associated with a gross total resection (GTR) of tumor correlated with EGFR and p53 mutations with regardless of localization, and poorly correlated to dimension. We suppose that performing a standard molecular analysis (IDH, EGFR, p53 and Ki67) is not sufficient to predict the behavior of a GBM in regards to overall survival (OS), nor to provide a deeper understanding of the meaning of the different genetic alterations in the DNA of cancer cells. A fine molecular profiling is feasible to precisely stratify the prognosis of GBM patients.

Dural plasmacytoma revealing multiple myeloma

2006 ◽  
Vol 104 (4) ◽  
pp. 608-610 ◽  
Author(s):  
Claire Haegelen ◽  
Laurent Riffaud ◽  
Marc Bernard ◽  
Beatrice Carsin-Nicol ◽  
Xavier Morandi
Keyword(s):  
Multiple Myeloma ◽  
Dura Mater ◽  
Systemic Disease ◽  
Immunohistochemical Analysis ◽  
Term Survival ◽  
Biological Studies ◽  
Ig G ◽  
Rule Out ◽  
Made In

✓The authors describe the case of a 72-year-old woman with dural plasmacytoma revealing an immunoglobulin (Ig) G-kappa multiple myeloma (MM). She presented with headaches and left hemiparesis. Magnetic resonance imaging demonstrated a right frontal extraaxial lesion arising from the dura mater, and biological studies revealed hypercalcemia, hyperproteinemia, and a serum gamma globulin peak. A diagnosis of IgG-kappa MM was based on microscopic examination and immunohistochemical analysis of the dural plasmacytoma as well as on signs of systemic myeloma after surgery. The patient died 3 years after the first symptoms of MM despite systemic chemotherapy and no recurrence of the dural plasmacytoma. Myelomatous involvement of the dura mater is a rare occurrence given that only three cases have been reported to date. Nevertheless, this pathological entity should be differentiated from solitary dural plasmacytoma (SDP) because the prognosis is radically different. Progression seems to be correlated with systemic disease in contrast to the long-term survival associated with SDP. Careful systemic evaluation should be made in such a presentation to rule out MM, which would require different management and has a different prognosis.

scholarly journals Does cellular senescence play an important role in the prognosis of sarcomatoid carcinoma of the pancreas?

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Toshihisa Kimura ◽  
Tamotsu Togawa ◽  
Atsushi Iida ◽  
Sakon Noriki ◽  
Yasunori Sato ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Sarcomatoid Carcinoma ◽  
Immunohistochemical Analysis ◽  
Point Of View ◽  
Term Survival ◽  
Long Term Survival ◽  
Carcinoma Of The Pancreas ◽  
Underlying Mechanisms ◽  
Short Term Survival

Abstract Aim Sarcomatoid carcinoma of the pancreas (SCP) is an extremely rare and aggressive disease with poor prognosis. We have already reported a rare case of SCP with long-term survival. In the present article, we investigate the underlying mechanisms of patient’s long-term survival from the point of view of cellular senescence which was examined in three SCP cases, including our reported case, using immunohistochemical analysis. Findings The expressions of cellular senescence marker were observed in the sarcomatous component of the patient with long-term survival but not observed in the other patients with short- term survival. Thus, we can speculate that cellular senescence might play an important role in the reduction of the cell proliferative and metastatic activities of sarcomatous cells, leading to long-term patient survival.

scholarly journals A validated integrated clinical and molecular glioblastoma long-term survival-predictive nomogram

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Sherise D Ferguson ◽  
Tiffany R Hodges ◽  
Nazanin K Majd ◽  
Kristin Alfaro-Munoz ◽  
Wajd N Al-Holou ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Cancer Center ◽  
Trial Participation ◽  
Karnofsky Performance Scale ◽  
Term Survival ◽  
Long Term Survival ◽  
Molecular Features

Abstract Background Glioblastoma (GBM) is the most common primary malignant brain tumor in adulthood. Despite multimodality treatments, including maximal safe resection followed by irradiation and chemotherapy, the median overall survival times range from 14 to 16 months. However, a small subset of GBM patients live beyond 5 years and are thus considered long-term survivors. Methods A retrospective analysis of the clinical, radiographic, and molecular features of patients with newly diagnosed primary GBM who underwent treatment at The University of Texas MD Anderson Cancer Center was conducted. Eighty patients had sufficient quantity and quality of tissue available for next-generation sequencing and immunohistochemical analysis. Factors associated with survival time were identified using proportional odds ordinal regression. We constructed a survival-predictive nomogram using a forward stepwise model that we subsequently validated using The Cancer Genome Atlas. Results Univariate analysis revealed 3 pivotal genetic alterations associated with GBM survival: both high tumor mutational burden (P = .0055) and PTEN mutations (P = .0235) negatively impacted survival, whereas IDH1 mutations positively impacted survival (P < .0001). Clinical factors significantly associated with GBM survival included age (P < .0001), preoperative Karnofsky Performance Scale score (P = .0001), sex (P = .0164), and clinical trial participation (P < .0001). Higher preoperative T1-enhancing volume (P = .0497) was associated with shorter survival. The ratio of TI-enhancing to nonenhancing disease (T1/T2 ratio) also significantly impacted survival (P = .0022). Conclusions Our newly devised long-term survival-predictive nomogram based on clinical and genomic data can be used to advise patients regarding their potential outcomes and account for confounding factors in nonrandomized clinical trials.

NTRK fusion analysis reveals enrichment in Middle Eastern BRAF wild-type PTC

2021 ◽  
Author(s):  
Yan Kong ◽  
Rong Bu ◽  
Sandeep Kumar Parvathareddy ◽  
Abdul K Siraj ◽  
Nabil Siraj ◽  
...  
Keyword(s):  
Gene Fusion ◽  
Middle Eastern ◽  
Fish Analysis ◽  
Gene Fusions ◽  
Wild Type ◽  
Pediatric Age Group ◽  
Middle Eastern Population ◽  
Fusion Analysis ◽  
Trk Inhibitors ◽  
Tumor Types

Objective: Fusions involving neurotrophic tyrosine receptor kinase (NTRK) are known oncogenic drivers in a broad range of tumor types. It recently gained attention as predictor of targeted therapy since selective NTRK inhibitors are now approved in US and Europe for patients with solid tumors harboring gene fusions. However, estimation of NTRK gene fusion/alteration frequency and its clinico-pathological characteristics in papillary thyroid cancer (PTC) is limited, especially in a population with high incidence for PTC like Middle Eastern population. This study aims to characterize the NTRK gene fusion frequency and investigate the utility of pan-Trk immunohistochemistry (IHC) as predictor of NTRK fusion in a large cohort of Middle Eastern PTC. Methods: FISH analysis for NTRK gene fusions and pan-Trk IHC was performed on 315 Middle Eastern PTCs. Correlation of NTRK gene fusion and protein expression with clinico-pathological markers and patient outcome were determined. Results: In our cohort, 6.0% (19/315) patients showed NTRK gene fusions and were significantly associated with pediatric PTC (p = 0.0143), lymph node metastasis (p = 0.0428) and BRAF wild-type tumors (p < 0.0001). Pan-Trk IHC was positive in 9.2% (29/315) of cases and significantly associated with NTRK fusions, with a sensitivity of 73.7% and specificity of 94.9% in this cohort. Conclusions: This study confirms the presence of NTRK fusions in Middle Eastern PTC which is significantly enriched in BRAF wild-type as well as pediatric age group and proposes the usefulness of IHC to screen for PTC patients with NTRK fusion that might benefit from TRK inhibitors.

scholarly journals A Peripheral Primitive Neuro-ectodermal Tumor (pPNET) of Larynx

2018 ◽  
Vol 26 (1) ◽  
pp. 69-72
Author(s):  
Raman Wadhera ◽  
Usha Sehrawat ◽  
Sharad Hernot ◽  
Pawan Kumar Gahlawat ◽  
Aman Jakhar
Keyword(s):  
Head And Neck ◽  
Malignant Tumors ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Neck Region ◽  
Immunohistochemical Analysis ◽  
Cystic Mass ◽  
Term Survival ◽  
Head And Neck Region

Introduction Primitive neuroectodermal tumors (PNETs) are malignant tumors comprised of small round cells of neuro-ectodermal origin that affect soft tissue and bone. Though the occurrence of pPNETs in the head and neck region is rare, these are aggressive malignant tumors, and long-term survival rates following diagnosis remain poor. Case Report In the present case, a tumour was located in larynx (as globular/cystic mass of epiglottis) of the patient and was diagnosed as pPNET. Immunohistochemical analysis indicated that tumor cells were positive for CD99 and NSE, focally positive for EMA but negative for synaptophysin and chromogranin. The mass was surgically excised with negative margins. In post op period patient was planned for post-op chemotherapy and radiotherapy. Conclusion pPNETs are very rare in head and neck region. Significant advances in the neoadjuvant and adjuvant chemotherapeutic regimens, as well as improved facility in diagnosing these tumors through cytogenetic and immunohistochemical analysis improves the long-term disease-free survival.

scholarly journals Investigating the Natural History and Prognostic Nature of NTRK Gene Fusions in Solid Tumors

2021 ◽  
Author(s):  
Limin Zhu ◽  
Brian Hobbs ◽  
Jason Roszik ◽  
Vijaykumar Holla ◽  
David S. Hong
Keyword(s):  
Natural History ◽  
Solid Tumors ◽  
Gene Fusion ◽  
Early Stage ◽  
The Cancer Genome Atlas ◽  
Cancer Center ◽  
Gene Fusions ◽  
Risk Of Progression ◽  
Md Anderson ◽  
Trk Inhibitors

Abstract BackgroundSeveral TRK inhibitors have demonstrated clinical efficacy in patients with solid tumors harboring NTRK gene fusions. However, the natural history and prognostic implications of NTRK fusions in solid tumors remain unknown.MethodsA cohort of 77 MD Anderson Cancer Center patients (MDACC) with NTRK gene fusions was identified and retrospectively compared to a second cohort from the Cancer Genome Atlas (TCGA) database. Due to paucity of events in early stage cancers and lack of TCGA data in rare tumors, 25 randomly selected MDACC patients were matched to 122 TCGA patients without NTRK gene fusion. Next we assessed the associations between NTRK gene fusion and overall (OS) and progression-free survivals (PFS).ResultsAmong the 77 MDACC patients with NTRK gene fusions, 18 NTRK fusion partners were identified. There were insufficient OS events for analysis in the matched cohort. PFS was not significantly different (p=0.49) between the NTRK-fusion positive MDACC patients (median PFS 786 weeks, 95% CI 317-NE) and the NTRK-fusion negative TCGA patients (median PFS NE). The adjusted hazard ratio comparing TCGA patients to MDACC patients was HR=0.72 (95% CI: 0.23-2.33), which trended towards a reduced rate of progression or death experienced by TCGA patients.ConclusionsThis study did not identify statistically significant associations between NTRK fusion and PFS. Nonsignificant trends estimated increases in the risk of progression or death events for patients with NTRK fusions when compared to matched controls. Our findings help illuminate the influence of NTRK fusions on the natural history of a variety of solid tumors.

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