scholarly journals Hormone receptor expression of colorectal cancer diagnosed during the peri-partum period

2019 ◽  
Vol 8 (8) ◽  
pp. 1149-1158 ◽  
Author(s):  
Jordyn Silverstein ◽  
Wesley Kidder ◽  
Susan Fisher ◽  
Thomas A Hope ◽  
Samantha Maisel ◽  
...  
Keyword(s):  
Significant Risk ◽  
Case Series ◽  
Stage Iv ◽  
Receptor Expression ◽  
Primary Tumors ◽  
Molecular Features ◽  
First Case ◽  
Hormone Receptor Expression ◽  
Generation Sequencing ◽  
Formalin Fixed

Background Colorectal carcinoma (CRC) during the peri-partum period is challenging to diagnose due to the overlapping symptoms of CRC and pregnancy. This is the first case series to investigate clinicopathologic, hormonal and molecular features of CRC diagnosed during the peri-partum period. We hypothesized that advanced presentations of CRC could possibly be mitigated by pregnancy-related hormonal factors. Methods We conducted a retrospective review of five women diagnosed with CRC during the peri-partum period and studied the clinical and molecular features of their cancer. Results All patients presented with stage IV CRC at diagnosis; three had primary tumors in the rectum and two had primary tumors in the sigmoid colon. The liver was the most common metastatic site (three of five women). Immunohistochemistry stains were negative for estrogen receptors alpha (ERα) and beta (ERβ), and one tumor demonstrated low-level positivity for PR (1%). Formalin-fixed and paraffin-embedded (FFPE) biopsies from each case were tested with next-generation sequencing and found that all tumors were mismatch repair (MMR) proficient, and three harbored a KRAS mutation. Germline testing showed no predisposition to CRC; however, several somatic variants of undetermined significance (VUS) were identified. Discussion CRC in the peri-partum period poses significant risk factors for presentations with advanced disease due to diagnostic challenges. While our study provides no evidence that pathogenesis of CRC during pregnancy is driven by elevated estrogen and/or progesterone levels during pregnancy, additional putative etiologic factors, including placental growth factors, the immunosuppressive state of pregnancy and other physiologic processes during pregnancy, warrant future study.

Update of NGS analysis of Italian survey of second tumors in patients with diagnosis of GIST (gastrointestinal stromal tumor).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23518-e23518
Author(s):  
Silvia Gasperoni ◽  
Francesca Castiglione ◽  
Margherita Vannucchi ◽  
Laura Papi ◽  
Elena Fumagalli ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Cox Model ◽  
Significant Risk ◽  
Low Risk ◽  
Second Primary ◽  
Primary Tumors ◽  
Molecular Features ◽  
Second Tumors ◽  
Second Primary Tumors

e23518 Background: In patients with GIST, literature reports a risk of second primary tumors between 4.5% and 33% with different distribution in the worldwide. The network of 7 italian EURACAN centers has collected clinical and molecular features of GIST patients with second primary tumors. Methods: We reviewed the clinical characteristics of 201 patients with GIST and second primary tumors in order to evaluate association between risk of dead and each possible factor, using Kaplan meier curve, log-rank test and Cox model for Hazard Ratio and it’s interval Confidence 95% estimation. Furthermore, NGS analysis ( 56 gene onco panel) in 72 patients with GIST was performed. Results: On the basis of the significant correlation previously observed between the Miettinen risk criteria of GIST (low/very low) and the incidence of second primary tumors (gastrointestinal tumors),P < 0.001 (Abstr 11032 ASCO 2019), we observed in these patients a median age of diagnosis of GIST of 68, with prevalent gastric site localization ( KIT exon 11 mutation), NF1 and Lynch (kit/pdgfra WT) syndromes in the low risk subgroup. The more frequent site of second epithelial tumor in gastrointestinal tract was the colon followed by gastric, pancreatic and biliary tract. In patients with GIST with low-very low risk according Miettinen classification, after a median follow-up period of 25 years, we have observed that the gastroenteric site of second tumors occurrence is significantly related to the survival (p < .0003). In the NGS analysis of the GIST we observed the pathogenetic somatic mutations in the following genes: BRCA 2 (p.Thr2125fs), but germline test negative, TP53 (p.Arg192*,p.Gly244Ser,p.His168Leu), RET (p.Lys120Asn, p.His168Leu, p.Thr930Met ), NRAS (p.Gly134Asp), CTNNB1 (p.Ser45Phe), MSH6 (P.Ala164Val), SMARCB1 (p.Arg192), VHL (p.Gly93Val), PTEN(p.Val158Ile, p.Asn323fs), STK1I (p.Arg40Cys), SMO (p.Glu194Lys), EGFR (p.Gly721Asp), ATM (p.Asp2708Asn), ERBB4 (p.Asn181Ile). Conclusions: In our analysis patients with GIST (low-very low classes according to Miettinen) have significant risk to death because of second primary tumors in gastrointestinal tract. Specific attention to gastrointestinal screening during the follow-up of GIST (low and very low risk) is required.

scholarly journals Utility of Whole-Genome Next-Generation Sequencing of Plasma in Identifying Opportunistic Infections in HIV/AIDS

2019 ◽  
Vol 13 (1) ◽  
pp. 7-11 ◽  
Author(s):  
Yang Zhou ◽  
Vagish Hemmige ◽  
Sudeb C. Dalai ◽  
David K. Hong ◽  
Kenneth Muldrew ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Opportunistic Infections ◽  
Case Series ◽  
Whole Genome ◽  
Next Generation ◽  
Invasive Procedures ◽  
First Case ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Hiv Aids

Background:AIDS-associated Opportunistic Infections (OIs) have significant morbidity and mortality and can be diagnostically challenging, requiring invasive procedures as well as a combination of culture and targeted molecular approaches.Objective:We aimed to demonstrate the clinical utility of Next-generation Sequencing (NGS) in pathogen identification; NGS is a maturing technology enabling the detection of miniscule amounts of cell-free microbial DNA from the bloodstream.Methods:We utilized a novel Next-generation Sequencing (NGS) test on plasma samples to diagnose a series of HIV-associated OIs that were diagnostically confirmed through conventional microbial testing.Results:In all cases, NGS test results were available sooner than conventional testing. This is the first case series demonstrating the utility of whole-genome NGS testing to identify OIs from plasma in HIV/AIDS patients.Conclusion:NGS approaches present a clinically-actionable, comprehensive means of diagnosing OIs and other systemic infections while avoiding the labor, expense, and delays of multiple tests and invasive procedures.

Clinical next generation sequencing (NGS) of fine needle aspiration (FNA) biopsies in non-small cell lung (NSCLC) and pancreatic cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11100-11100
Author(s):  
Matthew J. Hawryluk ◽  
Jeffrey S. Ross ◽  
Christine E. Sheehan ◽  
Jie He ◽  
Geneva Young ◽  
...  
Keyword(s):  
Needle Aspiration ◽  
Primary Tumors ◽  
Pancreatic Cancers ◽  
Manual Inspection ◽  
Formalin Fixed Paraffin ◽  
Pancreatic Masses ◽  
Formalin Fixed Paraffin Embedded ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Formalin Fixed

11100 Background: FNA is a common diagnostic procedure for the evaluation of pulmonary and pancreatic masses. We sought to determine whether NGS could be performed on these small specimens and to characterize heterogeneity across classes of genomic alterations (GA) in a subset of paired FNA and matched resected primary tumors. Methods: DNA was isolated from formalin fixed paraffin embedded (FFPE) sections of FNA cell blocks using 40µm total sections for NSCLC and 20µm total sections for pancreatic cancers in a CLIA-certified lab (Foundation Medicine). DNA sequencing was performed for 3,320 exons of 182 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer on indexed, adaptor ligated, hybridization-captured libraries to a median depth of 931x for the NSCLC and 416x for the pancreatic FNAs. Results: Genomic profiles were successfully generated from 19/19 of the NSCLC and 22/23 of the pancreatic FNA cases. We found 97 GA in the 19 NSCLC FNAs (range 2-9, average 5.1 GA per patient). 68% of the patients had GA in TP53 and 21% in KRAS. Only 16% (3/19) patients did not exhibit an actionable alteration. We found 99 GA in the 23 pancreatic cancer FNAs (range 0-12, average 4.3 per patient). 74% of the patients had GA in KRAS. There was 94% concordance of GA found in 4 matched FNA and primary tumor pairs for the pancreatic cases. For the single discordance, manual inspection of the reads of the discordant allele indicated evidence of loss of heterozygosity. Conclusions: NGS can be reliably performed on small FNA samples processed into cell blocks, and the GA discovered significantly correlates with the GA found in matched primary tumors. This study demonstrates the feasibility of NGS in analyzing FNA samples and further broadens the spectrum of commonly encountered specimen types to which this approach can be successfully applied.

Changes to the hormone receptor expression in patients treated with either tamoxifen or aromatase inhibitors as endocrine therapy for breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10543-10543
Author(s):  
S. Djahansouzi ◽  
V. Rostock ◽  
D. Niederacher ◽  
W. Rath ◽  
H. Bender ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Stage Iv ◽  
Receptor Expression ◽  
Tumor Biopsy ◽  
Before And After ◽  
Er Positive ◽  
Hormone Receptor Expression

10543 Background: Endocrine therapy (ET) of patients with hormone receptor (HR)-positive breast cancer (BC) is thought to adversely affect the HR expression of the tumor with time. In order to evaluate this, a study was undertaken comparing the HR status prior to adjuvant Tamoxifen (Tam) therapy and after progression in estrogen receptor (ER)-positive BC patients. Similarly, ET with aromatase inhibitors (AI) was investigated by comparing the HR status prior to AI therapy and after progression in ER-positive metastatic BC patients. Methods: A retrospective analysis of all stage I-III ER-positive BC patients who presented to the department between 1999 to 2004 and received adjuvant Tam for ≥ 6 month and had the tumor relapse (local recurrence or distant metastasis) confirmed by tumor biopsy. All patients were evaluated for ER and progesterone receptor (PR) status prior to ET as well as after relapse using immunohistochemistry. Similarly, stage IV ER-positive metastatic BC patients who received AI for ≥ 3 month with tumor biopsy prior and after AI therapy, were also analyzed in regards to their HR expression. Results: 44 eligible ER-positive BC patients constituted the Tam group. After relapse, 55% of the patients remained ER-positive, while 45% lost their positive ER status. For PR, 34 out of 44 patients were initially receptor positive (77%). Similarly, 15 out of 34 patients retained a positive PR expression (44%) and the 10 PR-negative patients showed no change in receptor expression following Tam. 5 eligible patients with ER-positive metastatic BC constituted the AI group. After progression, 4 out of 5 patients remained receptor positive, while 1 patient lost ER expression. For PR, 3 out of 5 patients were initially PR positive. After AI, only 2 patients showed a positive PR status. 2 patients were PR negative before and after AI therapy. Conclusions: Contrary to the belief that clinical progression under ET is probably as a result of the loss of HR expression, our data suggests that progression under ET does not necessarily result in the loss of HR expression. In fact, 55% of relapses under Tam and 80% of the progressions under AI remain ER positive, indicating potential susceptibility to other endocrine therapeutic agents. No significant financial relationships to disclose.

Mutational landscape of metastatic colorectal cancer: Aggregate insights from a molecular tumor board.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 837-837
Author(s):  
Mark Andrew Lewis ◽  
Derrick S. Haslem ◽  
Ramya Thota ◽  
Terence Duane Rhodes ◽  
Tyler Barker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Stage Iv ◽  
Tumor Board ◽  
Primary Tumors ◽  
Multiple Metastases ◽  
Molecular Tumor Board ◽  
Generation Sequencing

837 Background: The mutational landscape of metastatic colorectal cancer (CRC) is being elucidated by next-generation sequencing of both primary tumors and metastatic foci. In this study, we examined the results of all stage IV CRC cases submitted to our molecular tumor board (MTB). Methods: We performed a retrospective analysis of all patients who had next-generation sequencing performed between January 2015 and August 2017 on either their primary tumor and/or metastasis. Cases were presented at a MTB convened twice monthly. For the purposes of this study only pathogenic mutations were notated, not variants of unknown significance (VUS). Results: Eighty-seven unique patients had 97 specimens sequenced (28 primary tumors and 69 metastases). The primaries averaged 3 mutations per specimen (range: 1-6) whereas the metastases averaged 4 (range: 1-14, p=.25). The most common anatomic sites of submitted metastatic tissue were the liver (n=35, average mutations=4), followed by the lungs (n=10, average mutations=3) and the omentum/peritoneum (n=8, average mutations=3). Two patients had both a primary tumor and a metastasis sequenced, with a 33% rate of concordance in inter-specimen mutations. Five patients had multiple metastases sequenced, with a 53% rate of concordance in inter-specimen mutations; in every case of longitudinal sequencing, mutational burden increased in metastases over time. The most common mutation was apc (21% of all mutations), followed by p53 (16%) and then kras (13%). Candidacy for EGFR-directed therapy was found in 8 cases, and mismatch repair defects were detected in 5 cases. Conclusions: In stage IV CRC cases sent to our MTB, tissue from metastases was more commonly submitted for analysis than from the primary tumors. There is not necessarily concordance between mutations in primary tumors and metastases, nor among multiple metastases in the same patient. Sequencing at multiple time points in the disease course may allow observation of clonal evolution and dynamic adaptation of therapeutic targets.

scholarly journals Impact of estrogen and progesterone receptor expression on the clinical and molecular features of papillary thyroid cancer

2015 ◽  
Vol 173 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Guia Vannucchi ◽  
Simone De Leo ◽  
Michela Perrino ◽  
Stefania Rossi ◽  
Delfina Tosi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Progesterone Receptor ◽  
Papillary Thyroid Cancer ◽  
Reproductive Factors ◽  
Estrogen Receptor Α ◽  
Receptor Expression ◽  
Biological Behavior ◽  
Papillary Thyroid ◽  
Primary Tumors ◽  
Molecular Features

BackgroundThyroid cancer is highly prevalent in women during the fertile age, which suggests a possible impact of hormonal and reproductive factors.MethodsWe studied the expression of estrogen receptor α (ERα or ESR1) and progesterone receptor (PR or PGR) in 182 female and male patients with papillary thyroid cancer and correlated it to clinical and molecular features.ResultsERα and PR expression was found in 66.5 and 75.8% of patients respectively and was significantly correlated with larger tumor size and with a non-incidental diagnosis. Moreover, a trend toward a higher prevalence of local metastases was observed in ER- and PR-expressing tumors, which possibly indicates a more aggressive behavior. Interestingly, the occurrence of the ‘receptor conversion’ phenomenon, which has already been reported to have a negative prognostic effect in breast cancer, was demonstrated for the first time in thyroid tumors. Indeed, almost all of the ERα-positive primary tumors analyzed had ERα-negative metastatic lymph nodes. At the genetic analyses,BRAFV600Emutation was detected in 23.2% of the tumors and had a higher prevalence in larger tumors and in those with a stronger ERα or PR staining.ConclusionsThe whole of the findings reported in the present study argue for an association between ERα and PR sex hormone receptor expression and a more aggressive presentation. Although no impact on outcome was found, the evaluation of ERα and PR receptor expression could add insights into the biological behavior of tumors and could modify the follow-up, particularly in fertile women affected with persistent disease.

Lung Adenocarcinoma: Next Generation Sequencing and Outcome in Regional Community Oncology Setting

2021 ◽  
Author(s):  
Laura Skacel ◽  
Michael Babcock ◽  
Antoine Harb ◽  
Adam Curtis ◽  
Carter Liou ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Suppressor Gene ◽  
Smoking History ◽  
Published Data ◽  
Next Generation ◽  
Nccn Guidelines ◽  
Molecular Features ◽  
Generation Sequencing

Abstract PURPOSE: To analyze lung adenocarcinomas (LUAD) from a geographically unique population of rural Maine by next generation sequencing (NGS), correlate mutational findings with clinical features, patient outcomes and published data from other populations.METHODS: 210 consecutive LUADs diagnosed in 2017-2018 were analyzed for 50 oncogene/tumor suppressor gene hot spots by NGS. ALK, ROS-1, RET and MET were assessed by FISH, PD-L1 by immunohistochemistry. Findings were correlated with age, gender, smoking history, stage, overall (OS) and progression-free survival (PFS) and compared to pubished literature.RESULTS: The cohort included 113 (54%) women and 97 (46%) men, ages 33 to 91 (mean: 67.4 years), 52% active and 41% former smokers, 79 (38%) of advanced stage (stage IV). Most frequently detected mutations included TP53 (47.6%), KRAS (38.1%), EGFR (10%), STK11 (8.6%), BRAF (4.8%), MET (3.8%), ABL-1, ATM, CDKN2A, PIK3CA, (all 2.9%), RB-1 and NRAS (2.4%), APC, ERBB4, PTPN11, SMAD4, (all 1.9%), CTNNB1 and ERBB2 (both 1.4%). MET amplification occurred in 3.3%, RET and ALK/ROS-1 rearrangements in 1.4% and 0.5%, high PD-L1 expression in 35.2%. Treatment included surgery/radiation/adjuvant chemotherapy for stages I-II, definitive chemo/radiation therapy and immunotherapy for stage III, immunotherapy, chemo-immunotherapy, targeted therapy, palliative radiation for stage IV. At median of 26 months (minimum 21 month for surviving patients), OS/PFS were 44.3%/39.5%. Stage, male gender, TP53 mutation and KRAS/STK11 co-mutations correlated with adverse OS. In stages I-II, KRAS/TP53 co-mutation was unfavorable. CONCLUSION: NGS testing in a regional oncology setting identified established prognostic/therapeutic markers, as well as additional molecular features correlating with outcome. Our findings support prognostic stratification of LUAD based on the presence of gene mutations outside of the current NCCN guidelines: TP53, KRAS and STK11.

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