scholarly journals PFKFB2 Promoter Hypomethylation as Recurrence Predictive Marker in Well-Differentiated Thyroid Carcinomas

2019 ◽  
Vol 20 (6) ◽  
pp. 1334 ◽  
Author(s):  
Mateus Camargo Barros-Filho ◽  
Larissa Barreto Menezes de Lima ◽  
Mariana Bisarro dos Reis ◽  
Julia Bette Homem de Mello ◽  
Caroline Moraes Beltrami ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Predictive Marker ◽  
Recurrence Risk ◽  
Good Prognosis ◽  
Braf V600e ◽  
Free Survival ◽  
Thyroid Carcinomas ◽  
Potential Applicability ◽  
Poorly Differentiated ◽  
Well Differentiated

Despite the low mortality rates, well-differentiated thyroid carcinomas (WDTC) frequently relapse. BRAF and TERT mutations have been extensively related to prognosis in thyroid cancer. In this study, the methylation levels of selected CpGs (5-cytosine-phosphate-guanine-3) comprising a classifier, previously reported by our group, were assessed in combination with BRAF and TERT mutations. We evaluated 121 WDTC, three poorly-differentiated/anaplastic thyroid carcinomas (PDTC/ATC), 22 benign thyroid lesions (BTL), and 13 non-neoplastic thyroid (NT) tissues. BRAF (V600E) and TERT promoter (C228T and C250T) mutations were tested by pyrosequencing and Sanger sequencing, respectively. Three CpGs mapped in PFKFB2, ATP6V0C, and CXXC5 were evaluated by bisulfite pyrosequencing. ATP6V0C hypermethylation and PFKFB2 hypomethylation were detected in poor-prognosis (PDTC/ATC and relapsed WDTC) compared with good-prognosis (no relapsed WDTC) and non-malignant cases (NT/BTL). CXXC5 was hypomethylated in both poor and good-prognosis cases. Shorter disease-free survival was observed in WDTC patients presenting lower PFKFB2 methylation levels (p = 0.004). No association was observed on comparing BRAF (60.7%) and TERT (3.4%) mutations and prognosis. Lower PFKFB2 methylation levels was an independent factor of high relapse risk (Hazard Ratio = 3.2; CI95% = 1.1–9.5). PFKFB2 promoter methylation analysis has potential applicability to better stratify WDTC patients according to the recurrence risk, independently of BRAF and TERT mutations.

Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index > 20%

2018 ◽  
Vol 108 (2) ◽  
pp. 109-120 ◽  
Author(s):  
Atsuko Kasajima ◽  
Björn Konukiewitz ◽  
Naomi Oka ◽  
Hiroyoshi Suzuki ◽  
Akira Sakurada ◽  
...  
Keyword(s):  
Survival Rates ◽  
Disease Free Survival ◽  
Japanese Patients ◽  
Clinicopathological Parameters ◽  
Neuroendocrine Neoplasms ◽  
Free Survival ◽  
Tumor Group ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Disease Free

The clinicopathological features of lung neuroendocrine neoplasms (NEN) with a high proliferative index at the border area between atypical carcinoid and neuroendocrine carcinoma have not been investigated so far. The aim of this study was, therefore, to search for lung NENs which are well differentiated but show Ki67 values that overlap with those of poorly differentiated (PD)-NENs. Resected lung NENs from 244 Japanese patients were reviewed, and Ki67 indices were assessed in all tumors. The data were then correlated to clinicopathological parameters and patient outcome. Among 59 (24%) well-differentiated (WD)-NENs and 185 (76%) lung PD-NENs, 7 were defined as WD-NENs with Ki67 indices > 20%. The Ki67 indices of these tumors (mean 29%, range 24–36) were significantly lower than those of PD-NENs (mean 74%, range 34–99). All WD-NENs with Ki67 > 20% lacked abnormal p53 and loss of retinoblastoma 1 (Rb1) expression. In contrast, many PD-NENs expressed p53 (48%) and showed loss of Rb1 (86%). The 2- and 5-year disease-free survival rates in WD-NEN patients with Ki67 > 20% were lower than those of WD-NEN patients with Ki67 ≤20% (p < 0.01 for disease-free and overall survival). No statistical differences were detected between outcome of WD-NEN patients with Ki67 > 20% and those of PD-NEN. It is concluded that WD-NEN patients with Ki67 > 20% share the morphological and immunohistochemical features of WD-NEN patients with Ki67 ≤20%, but they have a worse prognosis, suggesting that this tumor group requires particular attention in future classifications and probably new therapeutic regimes.

scholarly journals Multimodal genetic features correlate with poor response to neoadjuvant chemoradiotherapy and high recurrence risk in Chinese patients with stage IB-IIA cervical cancer

2020 ◽  
Author(s):  
Yuchun Wei ◽  
Chuqing Wei ◽  
Chen Liang ◽  
Ning Liu ◽  
Zhenhao Fang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Therapy ◽  
Disease Free Survival ◽  
Poor Response ◽  
Recurrence Risk ◽  
Genetic Alterations ◽  
Chinese Patients ◽  
Free Survival ◽  
Caucasian Patients ◽  
Disease Free

Abstract Background Response of cervical cancer patients to neoadjuvant therapy differs from person to person. It remains unclear whether genetic alterations can predict response to neoadjuvant therapy and disease-free survival in cervical cancer.Methods 62 Chinese patients with stage IB-IIA cervical cancer were included in this study. Pre-treatment tumor tissues were profiled using a targeted next-generation sequencing assay. Genetic alterations were compared with those identified in the Western populations using the TCGA database. Pathological response and disease-free survival (DFS) were evaluated and their correlations with genetic alterations were analyzed.Results Genetic alterations in PIK3CA were prevalent in both Chinese and Caucasian populations. The mutation frequencies of TERT, POLD1, NOS2, and FGFR3 were significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were frequently mutated in Caucasian patients. Germline mutations were identified in 13 out of 62 Chinese patients and 57% of them occurred in DNA repair genes, such as BRCA1/2, TP53 and PALB2. High tumor mutation burden (TMB), TP53 polymorphism (rs1042522) and KEAP1 mutations were found to be associated with poor response to neoadjuvant therapy. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC amplification and TYMS polymorphism were associated with higher relapse rates of cervical cancer.Conclusion The similarity and difference of mutation landscape of Chinese and Caucasian patients suggested genetic background played a role in shaping the architecture of cervical cancer mutations. The associations of mutation feature of cervical cancer with patient response and tumor recurrence risk provided rationale to further validate and explore potential biomarkers for cervical cancer patients.

Well-Differentiated Neuroendocrine (Carcinoid) Tumors of the Extrahepatic Biliary Ducts

2010 ◽  
Vol 134 (7) ◽  
pp. 1075-1079
Author(s):  
Yvonne Saldanha Noronha ◽  
Anwar Sultana Raza
Keyword(s):  
Correct Diagnosis ◽  
Disease Free Survival ◽  
Needle Aspiration ◽  
Carcinoid Tumors ◽  
Endoscopic Retrograde ◽  
Free Survival ◽  
Accurate Preoperative Diagnosis ◽  
Biliary Ducts ◽  
Well Differentiated ◽  
Disease Free

Abstract Primary, well-differentiated neuroendocrine (carcinoid) tumors of the extrahepatic biliary ducts are an uncommon cause of biliary obstruction. As compared to cholangiocarcinomas, which are more commonly seen at this location, these tumors tend to behave less aggressively, and only one-third metastasize. Tumor size (&gt;2 cm) appears to be the best predictor of aggressive behavior. Surgery is the mainstay of treatment and complete resection offers prolonged disease-free survival. Accurate preoperative diagnosis is therefore important and can be made by examining brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography and/or endoscopic ultrasound-guided fine-needle aspiration. It is important to keep this entity in mind, especially when examining cytologic or small biopsy specimens, so that appropriate immunohistochemical stains can be used to arrive at the correct diagnosis.

Abstract Submission

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 526-526 ◽  
Author(s):  
L. J. Goldstein ◽  
R. Gray ◽  
B. H. Childs ◽  
D. Watson ◽  
S. G. Rowley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Oncotype Dx ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Breast Cancers ◽  
Free Survival ◽  
Increased Risk

526 Background: Evidence suggests modern chemotherapy (CT) regimens are only marginally more effective in HR-pos breast cancer (Berry et al. JAMA 2006: 295: 1658). Genomic classifiers may be useful for selection of high-risk subjects for more aggressive CHT. Methods: A case-cohort sample of 776 patients enrolled on E2197 who did (N=179) or did not have a recurrence after CT (if HR-neg) or CHT (if HR-pos) and had available tissue were evaluated for Oncotype DX™ Recurrence Score (RS). E2197 included 2885 evaluable patients with 0–3 positive nodes treated with four 3-week cycles of doxorubicin (60 mg/m2) plus cyclophosphamide 600 mg/m2 (AC) or docetaxel 60 mg/m2 (AT) and hormonal therapy (if HR-pos). Median follow-up was 76 months. Results: There was no difference in DFS between treatment arms. In multivariate analysis, RS was a significant predictor of recurrence in HR-pos disease (p=0.0007, recurrence risk 21% lower for each 10 point drop in RS, 95% confidence intervals 9% to 31%). Recurrence risk was significantly elevated for an intermediate RS 18–30 (n=138, hazard ratio [HR] 2.96 [p=0.0002]) or a high RS ≥ 31 (n=108, HR 4.00, p=0.0001) compared with low RS < 18(n=196), but not for high compared with intermediate RS (HR 1.34, [p=0.32]); results were similar if only HER2-neg disease was included. The 5-year relapse free interval(RFI), breast cancer free survival (BCFS), disease-free survival (DFS), and overall survival (OS) for patients with HR-pos, HER2-neg disease are shown below (%); patients with both node-neg or node-pos breast cancers whose RS was < 18 had excellent outcomes. Conclusions: Oncotype DX™ RS identifies individuals with HR-pos, HER2-neg breast cancer with 0–3 positive axillary lymph nodes at 3–4-fold increased risk of relapse despite standard CHT, and may serve as a means to distinguish between those who do well with standard CHT (RS <18) from those who may be suitable candidates for clinical trials evaluating alternative CT regimens or other strategies (RS ≥ 18). [Table: see text] [Table: see text]

Survival and recurrence of breast cancer patients with pathologic complete response after neoadjuvant chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12121-e12121
Author(s):  
Young Joo Lee ◽  
Sei-Hyun Ahn ◽  
Byung Ho Sohn ◽  
jong Won Lee ◽  
Il Yong Chung ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Good Prognosis ◽  
Her2 Status ◽  
Nodal Disease ◽  
Ki 67 ◽  
Free Survival ◽  
Disease Free

e12121 Background: Patients with Pathologic complete response after neoadjuvant chemotherapy is known to have a good prognosis. However, there is a difference depending on how the complete remission is defined. Methods: We analyzed basic characteristics and outcomes of 295 patients who had pathologic complete response defined as ypT0 and ypTis after neoadjuvant chemotherapy for breast cancer at Asan Medical Center in Seoul, Korea. Results: Median follow up period was 66.5 month(6~128 month). Overall survival was 94% at 5-year and 10-year. No difference was shown in preoperative age, grade, HR/HER2 status, Ki-67 level. Clinical stage III showed worst outcome(85.8%). Survival rate between ypT0N0 (98.8%) and ypTis (89.1%, p=0.00) and between ypT0/TisN residual (85.7%, p=0.00) was shown, but no statistical difference between ypTis and ypT0/Tis with residual nodes(p=0.539). Disease free survival also showed no statistical significance between age, HR/Her2 status. But patients with low Ki-67 level(0~20%)(68.2%) at diagnosis had worse DFS compared to high Ki-67 level(>20%)(87.5%)(P=0.013). No difference between intrinsic subtypes was shown. Patients with residual nodal disease had worse DFS(66.1%) than ypN0(89.1%)(p=0.00). DFS of ypT0N0 was 92.7% and ypTisN0(75.5%), ypT0/Tis with residual metastatic nodes(71.4%). There was no significant difference in type of chemotherapy regimen. Conclusions: Overall survival and disease free survival was different in ypT0N0 with ypTis and residual nodal disease. Good prognosis of pathologic complete response should be limited to cases in which the cancer has completely disappeared.

Clinical utility of immunohistochemistry using the novel anti-BRAF V600E antibody (clone RM8) for detection of the BRAF V600E mutant protein in papillary thyroid cancers

2018 ◽  
Vol 3 (1) ◽  
pp. 28 ◽  
Author(s):  
Arvind Krishnamurthy ◽  
Vijayalakshmi Ramshankar ◽  
Kanchan Murhekar ◽  
Vidyarani Shyamsundar ◽  
Pavithra B. Desai ◽  
...  
Keyword(s):  
Gold Standard ◽  
Braf V600e ◽  
Mutant Protein ◽  
Papillary Thyroid ◽  
Thyroid Cancers ◽  
Thyroid Carcinomas ◽  
Well Differentiated ◽  
Differentiated Thyroid Cancers ◽  
Kappa Agreement ◽  
Formalin Fixed

<p><strong>Background:</strong><strong> </strong>Molecular markers are gaining increasing importance as diagnostic and prognostic tools in patients with well differentiated thyroid cancers and BRAF V600E mutation has received wide attention in this regard <strong>Aim: </strong>To evaluate the clinical value of immunohistochemistry (IHC) using anti-BRAF V600E antibody (clone RM8) for detection of the BRAF V600E mutant protein in formalin-fixed and paraffin-embedded tissues of patients with papillary thyroid carcinomas. <strong>Materials and Methods: </strong>Patients who were managed for well differentiated thyroid cancers (<em>n </em>= 79) during the years 2005 and 2006 were included in the study. We evaluated the fidelity of the RM8 antibody specific for the BRAF V600E and compared its detection accuracy to real time polymerase chain reaction (PCR), which was taken as the gold standard. <strong>Results: </strong>Mutant BRAF V600E antibody was studied in 79 tissue sections, out of which 21 (26.5%) had staining for BRAF V600E in &gt;20% of the tumour cells and these were considered positive. The BRAF staining was moderate in 10 (47.6%), strong in 9 (42.5%) and very strong in 2 (9.5%) of sections stained. There was a statistically significant concordance (<em>P </em>= 0.000) with quantitative PCR (qPCR) for BRAF mutant taken as standard. (Kappa agreement: 0.881) Further, the receiver operating characteristics (ROC) curve showed that IHC can be used as a comparable standard to the qPCR. The highest possible sensitivity of 92% and specificity of 92.6% could be achieved by considering the cytoplasmic positivity of &gt;20% of cells with moderate to strong intensity (AUC = 0.923) <strong>Conclusion: </strong>Our study has shown that BRAF V600E IHC can be done in a conventional manner using rabbit monoclonal antibody RM8 on formalin-fixed and paraffin-embedded tissues of patients with papillary thyroid carcinomas. With a comparable diagnostic accuracy to the gold standard qPCR testing and with an added advantage of being cost effective, this technology can be considered for use as a first-line method for detection of BRAF V600E mutations, especially in resource constrained settings.</p>

scholarly journals Effectiveness of a Global Multidisciplinary Supportive and Educational Intervention in Thermal Resort on Anthropometric and Biological Parameters, and the Disease-Free Survival after Breast Cancer Treatment Completion (PACThe)

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Marie-Paule Vasson ◽  
Fabrice Kwiatkowski ◽  
Adrien Rossary ◽  
Sylvie Jouvency ◽  
Marie-Ange Mouret-Reynier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Physical Activity ◽  
Disease Free Survival ◽  
Recurrence Risk ◽  
Breast Cancer Treatment ◽  
Biological Parameters ◽  
Free Survival ◽  
One Year ◽  
Disease Free

A growing knowledge highlights the strong benefit of regular physical activity in the management of breast cancer patients, but few studies have considered biological parameters in their outcomes. In the prospective randomised trial after breast cancer treatment completion “PACThe,” we determined the effects of physical activity and nutritional intervention on the biological and anthropometric status of patients after one year of follow-up, and clarified the link between biomarkers at allocation and disease-free survival. 113 patients from the population of the “PACThe” study (n = 251) were analysed for biological parameters. Patients were randomized after chemotherapy in two arms: the intervention “SPA” receiving a 2-week session of physical training, dietary education, and physiotherapy (n = 57), and the control “CTR” (n = 56). Diet questionnaire, anthropometric measures, and blood parameters were determined at allocation and one year later. Survival and recurrence were checked over 7 years. Data were considered as a function of BMI, i.e., ≤25 for normal, 25–30 for overweight, and >30 for obese patients. At allocation, the large standard deviation for nutrient-intake values reflected an unbalanced diet for some patients in the three groups. At one-year follow-up, we noticed an increase in glucose (p<10−6), insulin (p<10−7), and adiponectin (p<0.022) plasma levels for both intervention arms, which were more accentuated for the >30 groups. Using the Cox model, we demonstrated that the highest testosterone plasma values were linked to an increase of the recurrence risk (HR [CI–95%] = 5.06 [1.66–15.41]; p=0.004). One-year after a global multidisciplinary supportive and educational intervention, we found few anthropometric and biological changes, mainly related to the patient’s initial BMI. We highlighted the importance of plasma testosterone in the evaluation of patient’s recurrence risk. Future studies would help better understand the mechanisms by which such multidisciplinary interventions could interact with breast cancer recurrence and define the most effective modalities.

scholarly journals The Influence of Pregnancy on the Recurrence of Cutaneous Malignant Melanoma in Women

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
M. Albersen ◽  
V. I. Westerling ◽  
P. A. M. van Leeuwen
Keyword(s):  
Malignant Melanoma ◽  
Disease Free Survival ◽  
Recurrence Risk ◽  
Cutaneous Malignant Melanoma ◽  
Stage I ◽  
Free Survival ◽  
Medical Databases ◽  
Significant Difference ◽  
History Of ◽  
Disease Free

Objective. The aim of this study was to determine whether pregnancy increases the recurrence risk of cutaneous malignant melanoma (CMM) in women with a history of stage I CMM.Methods. The electronic medical databases of Medline and Embase were explored. All 1084 obtained articles were screened on title and abstract using predetermined inclusion and exclusion criteria. A critical appraisal of relevance and validity was conducted on the remaining full text available articles.Results. Two studies were selected. Both studies revealed no significant difference in disease-free survival between women with stage I CMM and the control population.Conclusion. Pregnancy does not increase the recurrence risk of CMM in women with a history of stage I CMM.

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