The Molecular Pathology of Eye Tumors: A 2019 Update Main Interests for Routine Clinical Practice

2019 ◽  
Vol 19 (9) ◽  
pp. 632-664
Author(s):  
Sacha Nahon-Esteve ◽  
Arnaud Martel ◽  
Célia Maschi ◽  
Jean-Pierre Caujolle ◽  
Stéphanie Baillif ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Molecular Pathology ◽  
Biological Diversity ◽  
Locally Advanced ◽  
Molecular Classification ◽  
Molecular Data ◽  
Molecular Alterations ◽  
Molecular Tests ◽  
Advanced Tumor ◽  
Therapeutic Decisions

Over the last few years, we have seen constant development of molecular pathology for the care of patients with cancer. The information obtained from molecular data has transformed our thinking about the biological diversity of cancers, particularly in the field of ophthalmic oncology. It has reoriented the way in which therapeutic decisions and decisions concerning patient surveillance are made, both in the area of pediatric cancers, including rhabdomyosarcoma and retinoblastoma, and adult cancers, such as uveal melanoma and lymphomas. A better definition of the molecular classification of these cancers and of the different biological pathways involved is essential to the understanding of both the pathologist and the onco-ophthalmologist. Molecular tests based on targeted or expanded analysis of gene panels are now available. These tests can be performed with tumor tissue or biofluids (especially blood) to predict the prognosis of tumors and, above all, the benefit of targeted therapies, immunotherapy or even chemotherapy. Looking for the BAP1 mutation in uveal melanoma is essential because of the associated metastatic risk. When treating retinoblastoma, it is mandatory to assess the heritable status of RB1. Conjunctival melanoma requires investigation into the BRAF mutation in the case of a locally advanced tumor. The understanding of genomic alterations, the results of molecular tests and/or other biological tests predictive of a therapeutic response, but also of the limits of these tests with respect to the available biological resources, represents a major challenge for optimal patient management in ophthalmic oncology. In this review, we present the current state of knowledge concerning the different molecular alterations and therapeutic targets of interest in ophthalmic oncology.

scholarly journals From Molecular Classification to Targeted Therapeutics: The Changing Face of Systemic Therapy in Metastatic Gastroesophageal Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Adrian Murphy ◽  
Ronan J. Kelly
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Molecular Classification ◽  
Molecular Profiling ◽  
The Cancer Genome Atlas ◽  
Research Network ◽  
Phase Iii ◽  
Molecular Alterations ◽  
Barr Virus ◽  
Therapeutic Decisions

Histological classification of adenocarcinoma or squamous cell carcinoma for esophageal cancer or using the Lauren classification for intestinal and diffuse type gastric cancer has limited clinical utility in the management of advanced disease. Germline mutations in E-cadherin (CDH1) or mismatch repair genes (Lynch syndrome) were identified many years ago but given their rarity, the identification of these molecular alterations does not substantially impact treatment in the advanced setting. Recent molecular profiling studies of upper GI tumors have added to our knowledge of the underlying biology but have not led to an alternative classification system which can guide clinician’s therapeutic decisions. Recently the Cancer Genome Atlas Research Network has proposed four subtypes of gastric cancer dividing tumors into those positive for Epstein-Barr virus, microsatellite unstable tumors, genomically stable tumors, and tumors with chromosomal instability. Unfortunately to date, many phase III clinical trials involving molecularly targeted agents have failed to meet their survival endpoints due to their use in unselected populations. Future clinical trials should utilize molecular profiling of individual tumors in order to determine the optimal use of targeted therapies in preselected patients.

Predictors of treatment response in colorectal high-grade neuroendocrine carcinomas (HGNEC): A single institution experience.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 690-690
Author(s):  
Virginia Corbett ◽  
Nitya Prabhakar Raj ◽  
Virginia Kelly ◽  
Diane Lauren Reidy
Keyword(s):  
Treatment Options ◽  
Locally Advanced ◽  
Molecular Data ◽  
Molecular Characteristics ◽  
High Grade ◽  
Molecular Alterations ◽  
Predictors Of Response ◽  
Significant Difference ◽  
Molecular Sequencing ◽  
Neuroendocrine Carcinomas

690 Background: Colorectal high-grade neuroendocrine carcinomas (HGNEC) are aggressive tumors; treatment options consist of cis/carboplatin and 5FU-based chemotherapy. To date, choice of systemic therapy and sequencing of these drugs remains poorly understood. We examined clinical and molecular characteristics of colorectal HGNEC to better define predictors of response to cis/carboplatin and 5FU-based treatment. Methods: Patients (pts) with colorectal HGNEC treated at MSKCC from 1990-2018 were identified. MANEC (mixed adeno-neuroendocrine carcinoma) were excluded. Demographics, response to first- and second-line chemotherapy (by radiology report), outcomes, and molecular data (next-generation sequencing of tumor tissue), were collected. Results: 65 pts (mean age 58, 52% male) were identified, 13 (20%) with small cell carcinomas. 52 (79%) metastatic, 13 (20%) locally advanced. 27 (42%) received surgery and 11 (17%) received radiation. 56 pts received cis/carboplatin-based therapy, partial response (PR) in 18 (32%), stable disease (SD) in 4 (7%), and progressive disease (PD) in 31 (55%); 3 (5%) did not tolerate therapy. 28 pts received 5FU-based therapy, 13 PR in (46%), SD in 6 (21%), and PD in 7 (25%); 2 (7%) did not tolerate therapy. Median overall survival was 11.4 months. 21/65 (32%) pts underwent molecular sequencing of tumor; the most common alterations were KRAS 11 (52%), TP53 13 (62%), BRAF 7 (33%), APC 8 (38%), RB1 7 (33%). Most tumors (13/21, 62%) harbored alterations in genes traditionally altered in colorectal adenocarcinoma (KRAS/BRAF/APC) and in HGNEC (TP53/RB1). There was no significant difference in response to cis/carboplatin or 5FU-based chemotherapy based on location of the primary tumor (right vs. left) (p = 0.69/0.85), histologic features of the disease (p = 0.71/0.87), and for response to cis/carboplatin by molecular alterations in KRAS (p = 0.94), BRAF (p = 0.24), APC (p = 0.28), TP53 (p = 0.58), or RB1 (p = 0.28). Conclusions: Colorectal HGNEC are highly aggressive and more effective therapies are desperately needed. In this series, OS was poor. Clinical and molecular characteristics failed to predict response to cis/carboplatin and 5FU-based chemotherapy.

Recent Strategies for Treating Stage IV Gastric Cancer: Roles of Palliative Gastrectomy, Chemotherapy, and Radiotherapy

2016 ◽  
Vol 25 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Kunihiko Izuishi ◽  
Hirohito Mori
Keyword(s):  
Gastric Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Stage Iv Gastric Cancer ◽  
Palliative Gastrectomy ◽  
Advanced Tumor ◽  
Esophagogastric Cancer ◽  
Previously Treated

Recently, many strategies have been reported for the effective treatment of gastric cancer. However, the strategy for treating stage IV gastric cancer remains controversial. Conducting a prospective phase III study in stage IV cancer patients is difficult because of heterogeneous performance status, age, and degree of cancer metastasis or extension. Due to poor prognosis, the variance in physical status, and severe symptoms, it is important to determine the optimal strategy for treating each individual stage IV patient. In the past decade, many reports have addressed topics related to stage IV gastric cancer: the 7th Union for International Cancer Control (UICC) TNM staging system has altered its stage IV classification; new chemotherapy regimens have been developed through the randomized ECF for advanced and locally advanced esophagogastric cancer (REAL)-II, S-1 plus cisplatin versus S-1 in RCT in the treatment for stomach cancer (SPIRITS), trastuzumab for gastric cancer (ToGA), ramucirumab monotherapy for previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD), and ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW) trials; and the survival efficacy of palliative gastrectomy has been denied by the reductive gastrectomy for advanced tumor in three Asian countries (REGATTA) trial. Current strategies for treating stage IV patients can be roughly divided into the following five categories: palliative gastrectomy, chemotherapy, radiotherapy, gastric stent, or bypass. In this article, we review recent publications and guidelines along with above categories in the light of individual symptoms and prognosis. Abbreviations: APC: argon plasma coagulation; AVAGAST: anti-angiogenic antibody bevacizumab, the avastin in gastric cancer; BSC: best supportive care; CF: cisplatin and fluorouracil; CRP: C-reactive protein; DCF: docetaxel, cisplatin, and 5-FU; FISH: fluorescent in-situ hybridization; GJ: gastrojejunostomy; GPS: Glasgow Prognostic Score; HER: human epidermal growth factor receptor; HR: hazard ratio; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PS: performance status; QOL: quality of life; RAINBOW: ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma; RCTs: randomized controlled trials; REAL: randomized ECF for advanced and locally advanced esophagogastric cancer; REGARD: ramucirumab monotherapy for previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma; REGATTA: reductive gastrectomy for advanced tumor in three Asian countries; SEER: Surveillance Epidemiology and End Results; SEMS: self-expandable metal stents; SPIRITS: S-1 plus cisplatin versus S-1 in RCT in the treatment for stomach cancer; ToGA: trastuzumab for gastric cancer; TTP: time-to-progression; VEGFR: vascular endothelial growth factor receptor.

scholarly journals Bilateral Phyllodes Giant Tumor. A Case Report Analyzed by Array-CGH

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 825
Author(s):  
Francesco Fortarezza ◽  
Federica Pezzuto ◽  
Gerardo Cazzato ◽  
Clelia Punzo ◽  
Antonio d’Amati ◽  
...  
Keyword(s):  
Array Cgh ◽  
Phyllodes Tumor ◽  
Molecular Classification ◽  
Left Breast ◽  
Comparative Genomic ◽  
Fish Analysis ◽  
Molecular Tests ◽  
Giant Tumor ◽  
Metastatic Risk ◽  
The Right

The breast phyllodes tumor is a biphasic tumor that accounts for less than of 1% of all breast neoplasms. It is classified as benign, borderline, or malignant, and can mimic benign masses. Some recurrent alterations have been identified. However, a precise molecular classification of these tumors has not yet been established. Herein, we describe a case of a 43-year-old woman that was admitted to the emergency room for a significant bleeding from the breast skin. A voluminous ulcerative mass of the left breast and multiple nodules with micro-calcifications on the right side were detected at a physical examination. A left total mastectomy and a nodulectomy of the right breast was performed. The histological diagnosis of the surgical specimens reported a bilateral giant phyllodes tumor, showing malignant features on the left and borderline characteristics associated with a fibroadenoma on the right. A further molecular analysis was carried out by an array-Comparative Genomic Hybridization (CGH) to characterize copy-number alterations. Many losses were detected in the malignant mass, involving several tumor suppressor genes. These findings could explain the malignant growth and the metastatic risk. In our study, genomic profiling by an array-CGH revealed a greater chromosomal instability in the borderline mass (40 total defects) than in the malignant (19 total defects) giant phyllodes tumor, reflecting the tumor heterogeneity. Should our results be confirmed with more sensitive and specific molecular tests (DNA sequencing and FISH analysis), they could allow a better selection of patients with adverse pathological features, thus optimizing and improving patient’s management.

scholarly journals EPEN-45. NORMALIZING AND FACILITATING GENOMIC TESTING AT DIAGNOSIS IN PEDIATRIC EPENDYMOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii317-iii317
Author(s):  
Emily Owens Pickle ◽  
Ana Aguilar-Bonilla ◽  
Amy Smith
Keyword(s):  
Current Practice ◽  
Molecular Classification ◽  
Molecular Data ◽  
Molecular Profiling ◽  
Genomic Testing ◽  
Molecular Testing ◽  
Newly Diagnosed ◽  
Pediatric Ependymoma ◽  
Need Support ◽  
Almost All

Abstract The current consensus is that diagnosis and treatment of ependymoma should be based upon clinical and molecular classification. As we move into this paradigm, it is important all ependymoma cases undergo tumor collection, preservation, and molecular profiling at diagnosis. Our group of 6 sites gathered data on a cohort of 72 ependymoma cases. Sites were asked to report known molecular findings; 60/68 eligible cases (88%) did not include genetic findings. The low number of cases with molecular findings was surprising and since cases were diagnosed from as early as 2004, we asked collaborators to share their current practice in profiling (e.g., how frequently; in what setting were ependymomas sent for testing) to try and better understand current practice at sites. Since the publication of ependymoma molecular data, sites with a neuro-oncology program report sending almost all newly diagnosed ependymomas for molecular testing, whereas current practices at sites without dedicated neuro-oncology were less consistent. Profiling in the setting of relapse was more frequently reported at all centers. The implementation of molecular testing at diagnosis may need support at sites without dedicated neuro-oncology. Lead investigators for upcoming ependymoma clinical trials will need to think carefully about the logistics of profiling at centers where this is not standard practice at diagnosis.

scholarly journals Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus

2021 ◽  
Author(s):  
M. Schoemmel ◽  
◽  
H. Loeser ◽  
M. Kraemer ◽  
S. Wagener-Ryczek ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Locally Advanced ◽  
Tumor Escape ◽  
Inflammatory Microenvironment ◽  
Advanced Tumor ◽  
Tumor Stages ◽  
Tumor Center ◽  
Class 1

Abstract Introduction The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack. Patients and methods We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data. Results Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages. Discussion Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.

scholarly journals Extremely Locally Advanced Ovarian Malignant Mixed Mullerian Tumor in 37-Years-Old Female

PRILOZI ◽  
2017 ◽  
Vol 38 (1) ◽  
pp. 75-79
Author(s):  
Gjorgji Jota ◽  
Radomir Gelevski ◽  
Zoran Karadzov ◽  
Redzep Selmani ◽  
Magdalena Genadieva-Dimitrova ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Abdominal Wall ◽  
Locally Advanced ◽  
Clinical Signs ◽  
Left Ovary ◽  
Lateral Part ◽  
Ovarian Carcinomas ◽  
Advanced Tumor ◽  
Left Quadrant ◽  
Mullerian Tumor

Abstract Ovarian carcinosarcomas, rare variant of ovarian carcinoma, composed of both carcinomatous and mesenchymal components, solid and/or cystic, fleshy and hemorrhagic, frequently spreading beyond the ovary, are treated with surgery and adjuvant chemotherapy according to the treatment principles of ovarian carcinomas due to the small number of reported cases and lack of randomized studies. We report a case of a 37-year-old woman with clinical signs of extremely locally advanced tumor of ovarian origin, infiltrating the lower left quadrant of the abdominal wall with necrosis of the covering skin. Prior biopsy of the left ovary and omentum confirmed poorly differentiated serous adenocarcinoma. Bulky tumor the size of a child’s head, originating from the left ovary and infiltrating into the lower left quadrant abdominal wall was debulked with wide excision of the abdominal wall and creation of wide defect of the lower left part of abdominal wall covered with Dexon mesh. After the recovery, the medial part of the defect with exposed mesh was closed with pedicled tensor fasciae latae fasciomyocutaneous flap, while the lateral part of the defect was covered with split thickness skin graft. Optimal surgical cytoreduction and adjuvant chemotherapy in case of extremely locally advanced ovarian malignant Müllerian tumor provide satisfactory recurrence-free survival period.

scholarly journals The trends of uveal melanoma research in the past two decades and future perspectives.

2021 ◽  
Author(s):  
Khaled Ali Elubous ◽  
Ali Daoud Alebous ◽  
Hebah Ali Abous ◽  
Rawan Ali Elubous
Keyword(s):  
Uveal Melanoma ◽  
Web Of Science ◽  
The United States ◽  
Future Research ◽  
Genetic Mutations ◽  
Future Perspectives ◽  
Molecular Alterations ◽  
The Past ◽  
Clinical Biomarkers

Abstract PURPOSE Evaluation of the research trends in uveal melanoma in the past two decades.METHODS Data were extracted from the Web of Science database website. VOSviewer and Citespace software were used to analyze the retrieved data. RESULTS The leading country in terms of output and international collaboration is the United States. Research interest in genetic mutations, molecular pathways, and immunotherapy was remarkable in recent years. Most of the top ten journals are specialized in ophthalmology. In recent years the hotspots include future perspectives, BAB1 mutation, therapeutic target, and systematic reviews. The keywords with the strongest citation bursts are immunotherapy, outcome, and in situ hybridization. CONCLUSION The output of uveal melanoma research increased during the past two decades. Future research foci may include exploring different mutations role, immunotherapy, molecular alterations, and finding ideal clinical biomarkers.

Thymoma: From Chemotherapy to Targeted Therapy

2012 ◽  
pp. 475-479
Author(s):  
Nicolas Girard
Keyword(s):  
Targeted Therapy ◽  
Personalized Medicine ◽  
Molecular Characterization ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Tumor Burden ◽  
Advanced Tumor ◽  
Druggable Targets ◽  
Locally Advanced Tumor

Overview: Thymic malignancies are rare epithelial tumors that may be aggressive and difficult to treat. Thymomas are frequently eligible for upfront surgical resection. However, nearly 30% of patients present with locally advanced tumor at time of diagnosis, and chemotherapy is then used to reduce the tumor burden—possibly allowing subsequent surgery and/or radiotherapy. Metastatic and recurrent thymic malignancies may be similarly treated with chemotherapy. More recently, the molecular characterization of thymoma led to the identification of potentially druggable targets, laying the foundation to implement personalized medicine for patients.

scholarly journals Update Breast Cancer 2020 Part 2 – Advanced Breast Cancer: New Treatments and Implementation of Therapies with Companion Diagnostics

2020 ◽  
Vol 80 (04) ◽  
pp. 391-398
Author(s):  
Diana Lüftner ◽  
Andreas Schneeweiss ◽  
Andreas D. Hartkopf ◽  
Volkmar Müller ◽  
Achim Wöckel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Targeted Therapy ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Companion Diagnostics ◽  
Molecular Tests ◽  
New Treatments ◽  
First Time

AbstractFor patients with locally advanced or metastatic breast cancer, new and effective therapies such as CDK4/6 inhibitors, PARP inhibitors and a PD-L1 inhibitor have been introduced in recent years. This review presents an update on the available studies with their data. In addition, two innovative anti-HER2 therapies are presented (trastuzumab-deruxtecan and tucatinib) for which the results from new studies have been reported. Molecular tests offer the possibility of defining patient populations or also monitoring courses of therapy. This can help identify patients with specific characteristics in order to provide them with individually targeted therapy within the framework of studies. In a large study, the benefit of such a biomarker study was able to be described for the first time.

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