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Prognostic implications of PIK3CA amplification in curatively resected liposarcoma.

ABSTRACT: We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutations/amplifications in curative resected liposarcoma.A total of 125 liposarcoma tissue samples were collected over a 12-year period. PIK3CA mutations and gene copy number amplifications were analyzed by pyrosequencing and fluorescence in situ hybridization (FISH).Nine of the 105 liposarcomas (8.6%) had activating PIK3CA mutation. PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic tumors compared with well-differentiated/dedifferentiated tumors (13.3% vs. 2.2%, P=0.043). In FISH PIK3CA analysis, copy number gain was detected in 14 of the 101 tumors (13.9%): 11 (10.9%) tumors had increased gene copy number (polysomy) and 3 (3.0%) exhibited gene amplification. In survival analysis, patients with PIK3CA copy number gain had a worse prognosis compared to patients without PIK3CA amplification (median disease-free survival [DFS] 22.2 vs. 107.6 months p=0.005). By multivariate analysis, PIK3CA copy number gain was an independent prognostic factor for worse DFS (P=0.027; hazard ratio, 2.400; 95% confidence interval 1.105 to 5.213). PIK3CA mutation was not associated with DFS and overall survival.We demonstrated PIK3CA mutation and amplification in liposarcoma. PIK3CA copy number gain was an independent poor prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutations and amplifications in liposarcoma.

SUBMITTER: Kim JH

PROVIDER: S-EPMC5029721 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Prognostic implications of PIK3CA amplification in curatively resected liposarcoma.

Kim Joo Hoon JH Lee Jae Seok JS Kim Eo Jin EJ Park Kyu Hyun KH Kim Ki Hyang KH Yi Seong Yoon SY Kim Han Seong HS Cho Yong Jin YJ Shin Kyoo-Ho KH Ahn Joong Bae JB Hu Hyuk H Kim Kyung Sik KS Choi Young Deuk YD Kim Sunghoon S Lee Young Han YH Suh Jin-Suck JS Noh Sung Hoon SH Rha Sun Young SY Kim Hyo Song HS

Oncotarget 20160401 17

<h4>Background</h4>We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutations/amplifications in curative resected liposarcoma.<h4>Patients and methods</h4>A total of 125 liposarcoma tissue samples were collected over a 12-year period. PIK3CA mutations and gene copy number amplifications were analyzed by pyrosequencing and fluorescence in situ hybridization (FISH).<h4>Results</h4>Nine of the 105 liposarcomas (8.6%) had activating PIK3CA mutation. PIK3CA muta ...[more]

PMID: 27016421

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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC.MethodsWe investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers.ResultsPD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9, 12.5, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P > 0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P < 0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P = 0.023, P = 0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P = 0.006, P = 0.002).ConclusionsPIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.

Project description:BACKGROUND: A systematic review was conducted to evaluate the literature regarding the impact of follow-up on colorectal cancer patient survival and, in a second phase, recommendations were developed. METHODS: The MEDLINE, CANCERLIT, and Cochrane Library databases, and abstracts published in the 1997 to 2002 proceedings of the annual meeting of the American Society of Clinical Oncology were systematically searched for evidence. Study selection was limited to randomized trials and meta-analyses that examined different programs of follow-up after curative resection of colorectal cancer where five-year overall survival was reported. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee. RESULTS: Six randomized trials and two published meta-analyses of follow-up were obtained. Of six randomized trials comparing one follow-up program to a more intense program, only two individual trials detected a statistically significant survival benefit favouring the more intense follow-up program. Pooling of all six randomized trials demonstrated a significant improvement in survival favouring more intense follow-up (Relative Risk Ratio 0.80 (95%CI, 0.70 to 0.91; p = 0.0008). Although the rate of recurrence was similar in both of the follow-up groups compared, asymptomatic recurrences and re-operations for cure of recurrences were more common in patients with more intensive follow-up. Trials including CEA monitoring and liver imaging also had significant results, whereas trials not including these tests did not. CONCLUSION: Follow-up programs for patients with curatively resected colorectal cancer do improve survival. These follow-up programs include frequent visits and performance of blood CEA, chest x-rays, liver imaging and colonoscopy, however, it is not clear which tests or frequency of visits is optimal. There is a suggestion that improved survival is due to diagnosis of recurrence at an earlier, asymptomatic stage which allows for more curative resection of recurrence. Based on this evidence and consideration of the biology of colorectal cancer and present practices, a guideline was developed. Patients should be made aware of the risk of disease recurrence or second bowel cancer, the potential benefits of follow-up and the uncertainties requiring further clinical trials. For patients at high-risk of recurrence (stages IIb and III) clinical assessment is recommended when symptoms occur or at least every 6 months the first 3 years and yearly for at least 5 years. At the time of those visits, patients may have blood CEA, chest x-ray and liver imaging. For patients at lower risk of recurrence (stages I and Ia) or those with co-morbidities impairing future surgery, only visits yearly or when symptoms occur. All patients should have a colonoscopy before or within 6 months of initial surgery, and repeated yearly if villous or tubular adenomas >1 cm are found; otherwise repeat every 3 to 5 years. All patients having recurrences should be assessed by a multidisciplinary team in a cancer centre.

Project description:Background: Hepatitis B virus (HBV) infection has been associated with the risk and prognosis of many malignancies. Nevertheless, the association between HBV and the prognosis of breast cancer is unclear. The objectives of this study were to investigate the prognostic role of hepatitis B surface antigen (HBsAg) and to integrate HBsAg to establish nomograms for better prognostic prediction of very young patients with breast cancer. Methods: This analysis was performed retrospectively in a cohort of 1,012 consecutive very young (≤35 at diagnosis) patients who received curative resection for breast cancer. The significance of HBsAg in the prognosis of these patients was investigated. Univariate and multivariate analyses were used to identify independent variables for disease-free survival (DFS) and overall survival (OS). Nomograms were built based on those identified variables. Results: Overall, 140 of the 1,012 patients (13.8%) were seropositive for HBsAg. The median follow-up was 67.9 (95% CI, 64.4-71.4) months for the entire population. The HBsAg-positive cohort had significantly inferior DFS (HR, 1.66; 95% CI, 1.07-2.56; P = 0.021) and OS (HR, 1.75; 95% CI, 1.10-2.79; P = 0.016) as compared with the HBsAg-negative cohort. The rates of 10-year DFS and OS were 77.4 and 73.0% in the HBsAg-positive group and 84.1 and 85.6% in the HBsAg-negative group, respectively. In multivariable analysis, HBsAg status was identified as an independent significant unfavorable prognostic factor for DFS (P = 0.01) and OS (P = 0.04) in very young patients with breast cancer. Nomograms were established and displayed good calibration and acceptable discrimination. The C-index values for DFS and OS were 0.656 (95% CI: 0.620-0.691) and 0.738 (95% CI: 0.697-0.779), respectively. Based on the total prognostic scores (TPS) of the nomograms, 3 different prognosis groups were identified for DFS and OS. Conclusions: HBsAg is an independent unfavorable prognostic factor for DFS and OS in very young patients with curatively resected breast cancer, and nomograms integrating HBsAg provide individual survival prediction to benefit prognosis evaluation and individualized therapy.

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Prognostic implications of PIK3CA amplification in curatively resected liposarcoma.

Publications

Prognostic implications of PIK3CA amplification in curatively resected liposarcoma.

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