scholarly journals Comprehensive analysis of mutational and clinicopathologic characteristics of poorly differentiated colorectal neuroendocrine carcinomas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sun Mi Lee ◽  
Chang Ohk Sung
Keyword(s):  
Overall Survival ◽  
Survival Rates ◽  
Driver Genes ◽  
Clinicopathologic Characteristics ◽  
Targeted Next Generation Sequencing ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated ◽  
Oncogenic Driver ◽  
Generation Sequencing ◽  
Neuroendocrine Carcinomas

AbstractPoorly differentiated neuroendocrine carcinoma (NEC) is a rare subtype of colorectal cancer (CRC). This study aimed to investigate clinicopathologic characteristics of colorectal NECs and elucidate genomic differences and similarities between colorectal NECs and colorectal adenocarcinomas (ACs). A total of 30 colorectal NECs were screened for frequently identified CRC oncogenic driver genes by targeted next-generation sequencing of 382 genes. The median age of the patients was 67 years (range, 44 to 88 years). NECs occurred predominantly in the rectum (47%) and exhibited multiple adverse prognostic pathologic factors, including frequent lymphatic and vascular invasions, high rates of lymph node metastasis and distant metastasis and advanced TNM stage. The 1-, 3-, and 5-year overall survival rates of NEC patients were 46.7%, 36.4%, and 32.7%, respectively, with a median overall survival period of 11.5 months. In a molecular analysis, NECs showed high rates of BRAF mutation (23%), predominantly p.V600E (71%), and alterations in RB1 (47%), particularly deletion (57%). The frequencies and distributions of other genes, such as KRAS, APC, SMAD4, and PIK3CA, and microsatellite instability status were similar to those of ACs. These findings provide beneficial information for selecting therapeutic options, including targeted therapy, and a better understanding of the histogenesis of this tumour.

CDX2 Is a Useful Marker of Intestinal-Type Differentiation: A Tissue Microarray–Based Study of 629 Tumors From Various Sites

2005 ◽  
Vol 129 (9) ◽  
pp. 1100-1105 ◽  
Author(s):  
Lindsey B. De Lott ◽  
Carl Morrison ◽  
Saul Suster ◽  
David E. Cohn ◽  
Wendy L. Frankel
Keyword(s):  
Squamous Cell ◽  
Signet Ring Cell ◽  
Squamous Cell Carcinomas ◽  
Intestinal Type ◽  
High Grade ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated ◽  
Lung Adenocarcinomas ◽  
Colorectal Adenocarcinomas ◽  
Neuroendocrine Carcinomas

Abstract Context.—CDX2, a critical nuclear transcription factor for intestinal development, is expressed in intestinal epithelium and adenocarcinomas. Objectives.—To determine if CDX2 is a useful marker for intestinal-type differentiation and to correlate tumor histology with CDX2 staining in colorectal adenocarcinomas. Design.—Tissue microarrays from 71 colorectal adenocarcinomas, 31 hepatocellular carcinomas, 47 lung adenocarcinomas, 55 squamous cell carcinomas of the lung, 69 neuroendocrine carcinomas of the lung and 43 of the pancreas, 57 pancreatic adenocarcinomas, and 256 endometrial adenocarcinomas were stained with antibody against CDX2. Results.—CDX2 staining was positive in 51 (71.8%) of 71 colorectal cancers, including 38 (74.5%) of 51 well- or moderately differentiated tumors and 13 (65.0%) of 20 high-grade tumors. Of the high-grade tumors, 5 (71.4%) of 7 mucinous, 3 (100%) of 3 signet ring cell, and 5 (50.0%) of 10 poorly differentiated tumors were positive. Other tumors showing occasional CDX2 staining included 1 of 30 well- or moderately differentiated neuroendocrine carcinomas of the lung and 2 of 43 from the pancreas, 1 of 47 lung adenocarcinomas, 3 of 57 pancreatic adenocarcinomas, and 15 of 256 endometrial carcinomas. Hepatocellular, poorly differentiated neuroendocrine carcinoma of the lung and squamous cell carcinomas of the lung were not immunoreactive for CDX2. Conclusions.—CDX2 is a useful marker for intestinal-type differentiation, is rarely seen in tumors from the other sites evaluated, and may be useful in determining the site of origin for some metastatic tumors. However, CDX2 is not a sensitive marker for poorly differentiated colorectal carcinoma.

scholarly journals Factors affecting overall survival in ductal adenocarcinoma of the pancreatic head. Experience of one center

2021 ◽  
Vol 11 (1) ◽  
pp. 20-28
Author(s):  
D.  M. Kuchin ◽  
Ya.  I. Kolesnik ◽  
H.  G. Torgomyan ◽  
V.  E. Zagainov
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Vascular Invasion ◽  
Survival Rates ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
Factors Affecting ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Major Factors

Purpose. To identify major factors affecting the overall survival (OS). To select the cohort of patients with the best prognosis.Materials and methods. A retrospective analysis included data of 268 patients, 128 men and 140 women, with median age of 59±10,53 (30 to 83) years. For multivariate analysis of survival, patients were selected who underwent pancreaticoduodenectomy (PD) for ductal adenocarcinoma of the pancreatic head.Results. Our study demonstrated that histologically verified vascular invasion (detected only in 30 % of patients who underwent PD with resection of the major vessels) statistically significantly affected the OS. The increased CA19-9 level over 500 U / L (detected in 32,3 % of cases) is the factor that significantly worsens the OS. Patients with high grade adenocarcinoma have significantly better survival rates compared with patients who have moderately or poorly differentiated adenocarcinoma (p = 0.014; median 26 months, 95 % CI 4.4–47.6 versus median 17 months, 95 % CI 15–19, an median: 13 months, 95 % CI 5–21, respectively). Also, the use of adjuvant chemotherapy has a positive effect on long-term outcomes (p = 0.0001; median 26 months, 95 % CI 21.7–30.3 versus median 13 months, 95 % CI 11.3–14.7).Conclusion. A well-differentiated tumor and the use of adjuvant chemotherapy significantly increase the OS of patients. Poorly differentiated tumor, CA19-9 level over 500 U / mL and the histologically confirmed vascular invasion significantly worsen the prognosis of these patients.

scholarly journals The Clinicopathologic Characteristics and 3-Year Survival Rates of Epithelial Ovarian Cancer in Iran During 2011-2017

2018 ◽  
Vol 7 (4) ◽  
pp. 496-500
Author(s):  
Shahrzad Sheikh Hasani ◽  
Mitra Modares Gilani ◽  
Setareh Akhavan ◽  
Azam-Sadat Mousavi ◽  
Elham Saffarieh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Epithelial Ovarian Cancer ◽  
Mucinous Adenocarcinoma ◽  
Survival Rates ◽  
Newly Diagnosed ◽  
Clinicopathologic Characteristics ◽  
Cross Sectional ◽  
Treatment Type

Objectives: The aim of this study was to determine the 3-year overall survival among the epithelial ovarian cancer patients based on the histology, age, and the stage of the disease in Iran during 2011-2017. Materials and Methods: This study was a cross-sectional retrospective study that was conducted on 179 newly diagnosed patients with epithelial ovarian cancer, who had referred to the gynecologic cancers clinic in a referral training hospital in Tehran during 2011-2017. The patients’ data including the demographic characteristics of the patients, the stage of the disease, and the treatment type were analyzed based on the pathologic responses. Results: Among 220 newly diagnosed patients with epithelial ovarian cancer, 179 of them were suitable for the follow-up. There were 93 death and 85 living cases among these patients and the mean age of the patients was 50.5 ± 11.3. In addition, most of the patients were in stage 3 (60.9%) and 6.7% of them were in stage 4. The most common pathology was serous adenocarcinoma (70.9%). In this study, the overall survival rate had no connection with the type of tumor histology but it was related to the stage of the disease (P=0.05). Finally, there was no mortality in stage one and among the mucinous adenocarcinoma cases. Conclusions: The survival in the epithelial ovarian cancer was related to the stage of the disease and among all the pathologies, mucinous adenocarcinoma and clear cell carcinoma had the best survival rate.

Poorly differentiated neuroendocrine carcinoma-small cell of the gastrointestinal tract. Institutional experience

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14142-14142 ◽  
Author(s):  
J. M. O′connor ◽  
J. P. Sade ◽  
A. Pairola ◽  
E. Domenichini ◽  
A. Cabanne ◽  
...  
Keyword(s):  
Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Small Cell ◽  
Gi Tract ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Number Of Patients ◽  
Institutional Experience ◽  
Poorly Differentiated ◽  
Clinical Records

14142 Background: PDNEC-Small cell (OMS Clasification, grade III)of the GI tract are rare diseases. Small cel represent 0,1% to 1% of all GI malignancies, and are included in the group of PDNEC but: Do these group behave biologically and respond to treatment in the same way? Trying to elucidate this matter, we performed a retrospective analysis of our group of pts. with PDNEC. Methods: A database search was done. from 1997 to 2005 we found 31 pts. with PDNEC/Small cell from the GI Tract treated in our Centers. A review of the clinical records was performed with special interest in response rate and overall survival. interest. Results: 14 pts. were informed by the pathologist at diagnosis PDNEC and 17 pts. as small cell. Median age: 50 years (r 19–84). The most common primary site was Esophagus-Stomach (29%), followed by pancreas 9 pts. (29%. 9 pts.(29%) presented with metastatic disease with unknown orimary Sistemic symptoms were common. A majority of our pts. (61%) presented with overt metastases. The liver was involved in 14 pts. (61%) follow by lymph nodes in 5 (16%). The most common chemotherapy used was a combination Platinum based. Overall response rate was 43%. TTP for all pts were 7 months (95% IC 0.34–0.69). Overall survival was 12 months (95% IC 0,31–0,70). We observed differences in term of overall survival and TTP in favor of PDNEC (15 months vs 10 months and 8 vs 4 months respectively) pNS. Conclusions: PDNEC-Small cell had bad prognosis. In our Serie we found differences between both groups, although not statiscally significant (due to a low number of patients). Definitive data of treatment for the management of this group of pts. still lacks. No significant financial relationships to disclose.

Moderate versus aggressive chemotherapy of nodular lymphocytic poorly differentiated lymphoma.

1985 ◽  
Vol 3 (6) ◽  
pp. 769-775 ◽  
Author(s):  
E Z Ezdinli ◽  
J R Anderson ◽  
F Melvin ◽  
J H Glick ◽  
T E Davis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rates ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Complete Response ◽  
Entire Group ◽  
Free Survival ◽  
Prior Therapy ◽  
Poorly Differentiated ◽  
Disease Free

One hundred twenty-eight patients with purely nodular lymphocytic poorly differentiated lymphoma (NLPDL) without any prior therapy, entered on Eastern Cooperative Oncology Group protocol EST 2474, were analyzed for response, progression-free and overall survival. The restaged complete response rates with cyclophosphamide-prednisone (CP) (moderate regimen) of 54% compared favorably with those of the more intensive regimens; cyclophosphamide, vincristine, procarbazine and prednisone (COPP) (56%) and BCNU, cyclophosphamide, vincristine, and prednisone (BCVP) (53%). The toxicity of the regimens decreased from BCVP to COPP to CP. The median survival rate for the entire group was 7.8 years. Estimated progression-free survival at five years by regimen was COPP, 57%; BCVP, 26%; CP, 22% (P = .02). No other prognostic parameter significantly affected progression-free survival. In spite of the better progression-free survival of COPP-treated patients, the overall survival rates with the different induction regimens were similar. Maintenance therapy for patients in complete response at the end of induction therapy with periodic BCVP reinduction did not significantly affect the disease-free or overall survival. Cyclophosphamide-prednisone is a minimally toxic regimen effective in the treatment of NLPDL, but COPP, in view of its acceptable toxicity in this patient population and apparent superiority in providing a longer disease-free state, deserves further testing.

Pulmonary Neuroendocrine Carcinomas

2002 ◽  
Vol 126 (5) ◽  
pp. 545-553 ◽  
Author(s):  
Qin Huang ◽  
Alona Muzitansky ◽  
Eugene J. Mark
Keyword(s):  
Neuroendocrine Tumors ◽  
Neuroendocrine Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
The Body ◽  
Low Grade ◽  
Typical Carcinoid ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated ◽  
Neuroendocrine Carcinomas

Abstract Context.—Primary pulmonary neuroendocrine tumors are traditionally classified into 3 major types: typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LC) or small cell neuroendocrine carcinoma (SC). Confusion arises frequently regarding the malignant nature of TC and the morphologic differentiation between AC and LC or SC. Objective.—To provide clinicopathologic evidence to streamline and clarify the histomorphologic criteria for this group of tumors, emphasizing the prognostic implications. Patients.—To minimize variability in diagnostic criteria and treatment plans, we analyzed a group of patients whose diagnosis and treatment occurred at a single institution. We reviewed 234 cases of primary pulmonary neuroendocrine tumors and thoroughly studied 50 cases of resected tumors from 1986 to 1995. Results.—On the basis of morphologic characteristics and biologic behaviors of the tumors, we agree with many previous investigators that these tumors are all malignant and potentially aggressive. Based on our accumulated data, we have modified Gould criteria and reclassified these tumors into 5 types: (1) well-differentiated neuroendocrine carcinoma (otherwise called TC) (14 cases, with less than 1 mitosis per 10 high-power fields [HPF] with or without minimal necrosis); (2) moderately differentiated neuroendocrine carcinoma (otherwise called low-grade AC) (6 cases, with less than 10 mitoses per 10 HPF and necrosis evident at high magnification); (3) poorly differentiated neuroendocrine carcinoma (otherwise called high-grade AC) (10 cases, with more than 10 mitoses per 10 HPF and necrosis evident at low-power magnification); (4) undifferentiated LC (5 cases, with more than 30 mitoses per 10 HPF and marked necrosis); and (5) undifferentiated SC (15 cases, with more than 30 mitoses per 10 HPF and marked necrosis). The 5-year survival rates were 93%, 83%, 70%, 60%, and 40% for well, moderately, and poorly differentiated, and undifferentiated large cell and small cell neuroendocrine carcinomas, respectively. We found nodal metastasis in 28% of TC in this retrospective review, a figure higher than previously recorded. Conclusion.—Using a grading system and terms comparable to those used for many years and used for neuroendocrine tumors elsewhere in the body, we found that classification of pulmonary neuroendocrine carcinomas as well, moderately, poorly differentiated, or undifferentiated provides prognostic information and avoids misleading terms and concepts. This facilitates communication between pathologists and clinicians and thereby improves diagnosis and management of the patient.

scholarly journals Prognostic Impact of Subclonal TP53 Aberrations in Chronic Lymphocytic Leukemia Validated By a Robust Targeted Next Generation Sequencing Assay

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4380-4380
Author(s):  
Christian Brieghel ◽  
Christina Westmose Yde ◽  
Caspar da Cunha-Bang ◽  
Savvas Kinalis ◽  
Lone Bredo Pedersen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lymphocytic Leukemia ◽  
Prognostic Impact ◽  
Mutation Status ◽  
Tp53 Mutations ◽  
Targeted Next Generation Sequencing ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Generation Sequencing ◽  
Allelic Burden

Abstract Introduction/background: Clonal TP53 aberrations (del(17p) and/or TP53 mutations) in patients with chronic lymphocytic leukemia (CLL) correlates with a poor prognosis. Similar outcome has been demonstrated for patients with subclonal TP53 aberrations (Rossi, Blood, 2014). In order to guide novel targeted therapies approved in frontline treatment of TP53 aberrated (TP53+) CLL, development and clinical validation of robust assays for subclonal TP53 aberrations is warranted. Methods: DNA extracted from peripheral blood of CLL patients were diluted 1:5 in DNA derived from a cell line containing a known, but rare TP53 point mutation. TP53 exons 2-10 were PCR amplified from undiluted and diluted DNA in parallel using Phusion proofreading DNA polymerase and subsequently sequenced by targeted Next Generation Sequencing (tNGS) on Illumina MiSeq and HiSeq 2500. Sensitivity and specificity of the assay was tested by serial dilution of patient samples with known TP53 insertions, deletions or substitutions. Consecutive biobanked samples from CLL patients at a single institution were used for validation of the clinical impact of subclonal TP53 aberrations. Nucleotide variants were called by CLC Biomedical Genomics Workbench 3.0. An algorithm for detection of true mutations was developed based on comparison of the diluted and undiluted samples analyzed in parallel. Overall survival (OS) was analyzed using Kaplan-Meier. Results: The sensitivity and specificity of the assay was validated by detection of all 8 known TP53 aberrations in serial dilutions with the threshold of the assay established at 0.2% allelic burden. Known mutations were still detectable at 0.02% at the highest dilution. A test sample of patients with known del(17p) demonstrated TP53 mutations in 6 out of 7 patients (5 clonal and 1 subclonal TP53+) in accordance with previously reported frequencies of TP53 mutations among patients with del(17p). In total, 92 samples from 46 consecutive patients were analyzed. With a median coverage of 93,272 reads (98% above 20,688 reads, range: 5,153-720,025), 27 TP53 aberrations were found in 10 (22%) of the patients. Twenty-six (96%) mutations were subclonal with a median allelic burden of 0.9% (range: 0.2-97.5%). Seven patients had a single aberration. In two previously treated patients, 8 and 10 subclonal aberrations were detected. One patient with a known del(17p) also had subclonal TP53 mutations. Three patients had solely subclonal mutations below 1% allelic burden. Considered the hot spot region of TP53 in CLL, exons 4-8 harbored 93% of the detected mutations. The median (IQR) survival for TP53+ patients and patients with wild type TP53 (wt-TP53) was 37.5 (range: 2-106) and 104 (range: 9-113) months, respectively. In Kaplan-Meier analyses, TP53+ patients had a significantly poorer OS versus patients with wt-TP53 (p=0.00002, Figure 1). The two TP53+ long-term survivors both had an allelic burden below 1%, and the only other TP53+ patient with less than 1% allelic burden survived for 53 months, indicating that the prognostic impact of very low allelic burden TP53 aberrations needs further investigation. Conclusion: We have developed a robust assay for TP53 aberrations with a sensitivity of 0.2% allelic burden based on an algorithm including a dilution step. In an initial test cohort of 46 patients, 10 patients demonstrated TP53 mutations as low as 0.2% allelic burden that significantly affected OS. Validation of the clinical impact of subclonal TP53 aberrations is ongoing based on our consecutive biobank with 600+ patients. Establishment of a new cut-off for clinical treatment decisions based on subclonal TP53 aberrations is warranted. Figure 1 Overall survival in 46 consecutive CLL patients based on TP53 mutation status shows significant difference (p=0.00002) between patients withwild type TP53 (wt-TP53) and TP53 mutations (TP53+) as low as 0.2% allelic burden. Figure 1. Overall survival in 46 consecutive CLL patients based on TP53 mutation status shows significant difference (p=0.00002) between patients withwild type TP53 (wt-TP53) and TP53 mutations (TP53+) as low as 0.2% allelic burden. Disclosures Niemann: Gilead: Consultancy; Abbvie: Consultancy; Roche: Consultancy; Janssen: Consultancy.

IPMNs with co-occurring invasive cancers: neighbours but not always relatives

Gut ◽  
2018 ◽  
Vol 67 (9) ◽  
pp. 1652-1662 ◽  
Author(s):  
Matthäus Felsenstein ◽  
Michaël Noë ◽  
David L Masica ◽  
Waki Hosoda ◽  
Peter Chianchiano ◽  
...  
Keyword(s):  
Invasive Carcinoma ◽  
Ductal Adenocarcinoma ◽  
Precursor Lesions ◽  
Single Institution ◽  
Intraductal Papillary Mucinous Neoplasms ◽  
Driver Genes ◽  
Cancer Driver ◽  
Targeted Next Generation Sequencing ◽  
Mucinous Neoplasms ◽  
Generation Sequencing

ObjectiveIntraductal papillary mucinous neoplasms (IPMNs) are precursor lesions that can give rise to invasive pancreatic carcinoma. Although approximately 8% of patients with resected pancreatic ductal adenocarcinoma have a co-occurring IPMN, the precise genetic relationship between these two lesions has not been systematically investigated.DesignWe analysed all available patients with co-occurring IPMN and invasive intrapancreatic carcinoma over a 10-year period at a single institution. For each patient, we separately isolated DNA from the carcinoma, adjacent IPMN and distant IPMN and performed targeted next generation sequencing of a panel of pancreatic cancer driver genes. We then used the identified mutations to infer the relatedness of the IPMN and co-occurring invasive carcinoma in each patient.ResultsWe analysed co-occurring IPMN and invasive carcinoma from 61 patients with IPMN/ductal adenocarcinoma as well as 13 patients with IPMN/colloid carcinoma and 7 patients with IPMN/carcinoma of the ampullary region. Of the patients with co-occurring IPMN and ductal adenocarcinoma, 51% were likely related. Surprisingly, 18% of co-occurring IPMN and ductal adenocarcinomas were likely independent, suggesting that the carcinoma arose from an independent precursor. By contrast, all colloid carcinomas were likely related to their associated IPMNs. In addition, these analyses showed striking genetic heterogeneity in IPMNs, even with respect to well-characterised driver genes.ConclusionThis study demonstrates a higher prevalence of likely independent co-occurring IPMN and ductal adenocarcinoma than previously appreciated. These findings have important implications for molecular risk stratification of patients with IPMN.

Sign in / Sign up

Export Citation Format

Share Document