Clínica, auxología y calidad de vida en cincuenta niños, niñas y adolescentes con síndromes de sobrecrecimiento corporal segmentario de un único centro / Clinical and auxological characteristics and quality of life of 50 children and adolescents with segmental overgrowth syndromes at a single center

Introducción. Los síndromes de sobrecrecimiento corporal segmentario son un grupo de enfermedades poco frecuentes caracterizadas por exceso de crecimiento en una o más partes del cuerpo relacionadas, en su mayoría, con mutaciones en mosaico en la vía de señalización AKT/PI3K/mTOR y RAS-MAPK. Nuestro objetivo fue analizar las características clínicas y auxológicas, y la calidad de vida relacionada a salud (CVRS) en este grupo de pacientes en un hospital de tercer nivel de atención. Población y métodos. Estudio transversal de una cohorte en seguimiento. Se analizaron edad, sexo, datos sociodemográficos, mediciones antropométricas del segmento afectado y del contralateral, complicaciones, tratamiento, calidad de vida (PedsQL4.0) y dolor. Se calcularon medidas centrales y de dispersión. Se realizó análisis univariado entre calidad de vida y variables incluidas. Resultados. Se incluyeron 50 pacientes, 29 varones. Mediana de edad 9,95 (r 1,44-17,81) años. El diagnóstico más frecuente fue síndrome de sobrecrecimiento relacionado a PIK3CA (PROS) (37/50). Mediana de número de segmentos afectados 2 (r: 1-7) por niño. Cuarenta casos presentaron malformación vascular; 20, capilar. El dolor (24/50) fue la complicación más frecuente. Treinta y un pacientes mostraron asimetría de longitud de miembros inferiores, < 5 cm. La estatura se ubicó entre los centilos 50 y 97 en la mayoría de los niños. Menor CVRS se observó en mujeres, en pacientes con malformación vascular compleja y necesidades básicas insatisfechas (NBI). Conclusiones. PROS fue el diagnóstico más frecuente. El dolor fue una complicación frecuente. La CVRS fue menor en mujeres, pacientes con malformación vascular combinada y NBI.

Introduction. Segmental overgrowth syndromes are a group of rare diseases characterized by overgrowth in one or more parts of the body, mostly related to mosaic mutations in the AKT/PI3K/mTOR and RASMAPK signaling pathway. Our objective was to analyze the clinical and auxological characteristics and health-related quality of life (HRQoL) in this group of patients at a tertiary care hospital. Population and methods. Cross-sectional study of a follow-up cohort. Age, sex, sociodemographic data, anthropometric measurements of the affected and contralateral segments, complications, treatment, quality of life (PedsQL 4.0), and pain were analyzed. Central and dispersion measures were estimated. A univariate analysis between the quality of life and study variables was done. Results. A total of 50 patients were included; 29 were males. Median age: 9.95 (r: 1.44­17.81) years. The most common diagnosis was PIK3CA-related overgrowth spectrum (PROS) (37/50). The median number of affected segments was 2 (r: 1­7) per patient. Vascular malformations were observed in 40, and capillary malformations, in 20 patients. Pain was the most common complication (24/50). An asymmetry of the lower extremities of < 5 cm was observed in 31 patients. In most children, height was between the 50th and 97th percentiles. A lower HRQoL was observed among girls, patients with complex vascular malformations, and those with unmet basic needs (UBNs). Conclusions. PROS was the most common diagnosis. Pain was the most common complication. HRQoL was lower among girls, patients with combined vascular malformations, and those with UBNs.

Relationships between PIK3CA gene status and clinical features and prognosis in triple-negative breast cancer / 国际肿瘤学杂志

Objective:To detect the status of PIK3CA in triple-negative breast cancer (TNBC) , and to analyze the relationships between PIK3CA mutation and clinical features and its impact on prognosis.Methods:From January 1, 2016 to December 31, 2018, 50 patients with primary TNBC admitted to Xinxiang Central Hospital of Henan Province were collected. The PIK3CA mutation status was detected, and the relationships between PIK3CA mutation and clinical characteristics of patients with TNBC and its impact on prognosis were analyzed.Results:PIK3CA gene mutation was detected in 9 of 50 TNBC patients, with a mutation frequency of 18.0%. H1047R mutation was found in 4 cases, E545K mutation in 3 cases and E542K mutation in 2 cases. PIK3CA gene mutation was not associated with age ( χ2=3.55, P=0.060) , tumor location ( χ2=1.01, P=0.315) , tumor size ( χ2<0.01, P>0.999) , lymph node status ( χ2=0.76, P=0.385) , clinical stage ( χ2=0.65, P=0.420) , Ki-67 value ( χ2<0.01, P>0.999) , P53 status ( χ2=0.02, P=0.894) and human epidermal growth factor receptor-2 (HER-2) status ( χ2=1.65, P=0.200) . Prognostic analysis showed that 3-year disease-free survival rates of wild-type PIK3CA patients was significantly higher than that of mutant PIK3CA patients (80.5% vs. 11.1%, χ2=28.23, P<0.001) . Conclusion:The frequency of PIK3CA gene mutation is higher in TNBC patients. There is no correlation between PIK3CA mutation and clinicopathologic features in TNBC patients. PIK3CA gene mutation may be significantly associated with poor prognosis of TNBC patients.

Views on the Current Diagnosis and Treatment of PIK3CA-Related Overgrowth Spectrum / 罕见病研究

PIK3CA-related overgrowth spectrum (PROS) is a rare condition characterized by disproportionate overgrowth of head, neck, trunk, or extremity, caused by PIK3CA gene mutation. This condition has negative impact on the physical appearance, functions, and psychosocial well-being of the patients. The condition causes social and economic burden, too. The gold standard for the diagnosis of PROS is the genetic testing using somatic tissue, but detecting low-level mosaic mutations of PIK3CA gene remains a challenge. There is no specific treatment now. Supportive management including surgery and other interventions have limited effects in improving cosmetic outcome and functions. Multidisciplinary collaboration is the key to the success of managing PROS. Targeted gene therapy is promising in improving the outcome for patients with severe PROS. Patients diagnosed with negative genetics test by the clinical measures are often ineligible for novel gene therapy. This article reviews the clinical manifestations, diagnosis, and treatments of PROS, aiming to improve the current understanding of this rare condition.

Clinical characteristics of 170 cases of macrodactyly / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical characteristics of 170 cases of macrodactyly.@*METHODS@#Medical records of 170 macrodactyly patients at Beijing Jishuitan Hospital between March 2006 and October 2019, including demographic characteristics, clinical presentations, anatomical distributions, X-rays, pathological findings, and treatments, were reviewed. PIK3CA mutation analyses of 12 patients were also reviewed.@*RESULTS@#Disease incidence was similar across sex and geographical regions. Multiple-digit involvement was 3.9 times more frequent than single-digit involvement. In upper deformit: ies, the index finger, middle finger and thumb were mostly involved, and the second and third toes were the most affected on the foot. Two digits were affected more often than three digits, with the affected multiple digits were adjacent most time. The cases of progressive macrodactyly, in which the affected digits grew at a faster rate than the unaffected digits, were found more than static type. Most of progressive macrodactyly were noticed at birth. In terms of nerve involvement, affected fingers mostly occurred in the median nerve innervation area (79.4%) accompanied by median nerve and brunches enlargement and fat infiltration, i.e., nerve territory oriented; affected toes mostly occurred in the medial plantar nerve innervation area (89.1%), marked with overgrowth of adipose tissue with a lesser degree of neural overgrowth, i.e., lipomatous. Only 17 cases had comorbid of syndactyly. The metacarpal bones were involved only in progressive type of macrodactyly. Ten of the 12 cases subjected to PIK3CA mutation analysis were positive. Among all tested specimens, PIK3CA mutation levels ranged from 7% to 27%. In terms of tissue sources in which a mutation was found, adipose tissue had the highest mutation detection rate, followed by nerve and skin. All the DNA samples of blood from the 12 PIK3CA mutation-positive patients were negative.@*CONCLUSION@#Macrodactyly fingers mostly occurred in the median nerve innervation area accompanied by median nerve and brunches enlargement and fat infiltration. The index and middle fingers were mostly involved. Macrodactyly toes mostly occurred in the medial plantar nerve innervation area, marked with overgrowth of adipose tissue with a lesser degree of neural overgrowth. The second and third toes were the most affected on the foot. A high proportion (83%) of isolated macrodactyly patients carry activating PIK3CA mutations. Adipose, nerve, and skin tissues provide the highest PIK3CA mutation detection yield among all types of tissue studied.

Germline and Somatic mutations in postmenopausal breast cancer patients

OBJECTIVES: In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations. METHODS: Forty-nine postmenopausal (>55 years) and forty-one young (≤35 years) BC patients were included in this study. The postmenopausal group included patients who reported a positive family history of cancer. For these patients, gBRCA1/BRCA2 were sequenced using next-generation sequencing (NGS) or Sanger sequencing. Data for gBRCA in young patients were already available from a previous study. DNA from formalin-fixed, paraffin-embedded (FFPE) tumors was obtained from 27 postmenopausal and 41 young patients for analyzing exons 9 and 20 of PIK3CA. The association between gBRCA1/BRCA2 and somatic mutations in PIK3CA was investigated. RESULTS: The overall frequency of gBRCA1/BRCA2 among the 49 postmenopausal patients was 10.2%. The frequencies of somatic mutations in PIK3CA in the postmenopausal and young patients were 37% and 17%, respectively (ns). The most common PIK3CA mutation was found to be E454A. Nonsense and frameshift mutations, which may counteract the oncogenic potential of PIK3CA were also detected. Regardless of age, 25% of BRCA1/BRCA2 mutation carriers and non-carriers , each, had PIK3CA somatic mutations. CONCLUSIONS: Data obtained indicate that BRCA1/BRCA2 gene testing may be considered for postmenopausal patients with BC who have a family history of cancer. Although some of them are not considered pathogenic, somatic variants of PIK3CA are frequently observed in BC patients, especially in postmenopausal patients.

Prevalence and Prognostic Role of PIK3CA/AKT1 Mutations in Chinese Breast Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1 mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis. MATERIALS AND METHODS: Tumors from 507 breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013. Whole exons of AKT1 and PIK3CA were detected in fresh-frozen tumors using next-generation sequencing, and correlations between PIK3CA/AKT1 mutations and clinicopathological features were analyzed. RESULTS: The AKT1 mutation was found in 3.6% (18/507) of patients. Tumors from patients that carried the AKT1 mutation were estrogen receptor (ER)+/progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2)‒ and were more likely to have high expression levels of Ki67. The prevalence of the PIK3CA mutation was 46.5% (236/507), and 35 patients carried two or three variants of the PIK3CA gene. PIK3CA mutations were associated with ER+/PR+/HER2‒ status. The prognosis of patients with one mutation in PIK3CA (or PIK3CA/AKT1) was not significantly different than that of patients with wild-type PIK3CA (or PIK3CA/AKT1), while patients with two or three variants in PIK3CA (or PIK3CA/AKT1) exhibited poorer outcomes in the entire group and in all three subgroups (ER+, HER2‒, Ki67 high), particularly with respect to overall survival. CONCLUSION: A high frequency of somatic PIK3CA mutations was detected in Chinese breast cancer patients. In addition to the mutation frequency, the tumor mutational burden of the PIK3CA and AKT1 genes should also be of concern, as they may be associated with poor prognosis.

Silencing the PIK3CA Gene Enhances the Sensitivity of Childhood Leukemia Cells to Chemotherapy Drugs by Suppressing the Phosphorylation of Akt

PURPOSE: This study aimed to investigate the effects of PIK3CA on the sensitivity of acute B lymphocytic leukemia cells (Nalm-6 cells) to chemotherapy drugs. MATERIALS AND METHODS: Children's normal B lymphocytes and Nalm-6 cells were cultured. Nalm-6 cells were transfected with PIK3CA siRNA (siPIK3CA group) or its negative control (PIK3CA-Control group). Normal Nalm-6 cells were named Mock group. Nalm-6 cells transfected by PIK3CA siRNA were treated with Akt inhibitor (siPIK3CA+Akti-1/2 group). mRNA and protein expression was detected by qRT-PCR and Western blot. Proliferation and sensitivity to chemotherapeutic drugs was detected by MTT assay. Cell cycle and apoptosis was explored by low cytometry. Transwell assay was performed to test invasion. RESULTS: PIK3CA mRNA (p=0.008) and protein (p=0.006) expression was higher in Nalm-6 cells than that in normal B lymphocytes. Compared with the Mock group and PIK3CA-Control group, Nalm-6 cells of the siPIK3CA group had lower OD495 values (all p < 0.05) and invasion cell numbers (p=0.03 and p=0.025), as well as a higher proportion of G0/G1 phase cells (p=0.020 and p=0.022), percentage of apoptosis (p=0.016 and p=0.022), and inhibition rate (all p < 0.05). pAkt expression in the siPIK3CA group (p=0.026 and p=0.031) and siPIK3CA+Akti-1/2 group (p=0.019 and p=0.023) was lower than that in the Mock group. CONCLUSION: PIK3CA silencing inhibited Nalm-6 cell proliferation and invasion, and promoted their apoptosis and sensitivity to chemotherapeutic drugs, potentially through regulation of the PI3K/AKT signaling pathway.

BRAF/ KRAS and PIK3CA mutation characteristics and clinical significance in primary small cell lung caner / 中华放射肿瘤学杂志

Objective To detect the frequency of BRAF/ KRAS and PIK3CA mutations in the small cell lung cancer (SCLC) specimens from a large population of Chinese patients and to analyze the gene mutation and clinical characteristics. Methods A total of 557 samples were collected from SCLC patients from 2009 to 2014.BRAF,KRAS,PIK3CA,NRAS and MEK1 gene mutations were detected by the dideoxy sequencing. Chi-square test was adopted to analyze the correlation between clinical factors and gene mutation. Kaplan-Meier method was utilized for survival analysis. Cox model was used for multivariate prognostic analysis. Results BRAF mutations were detected in 13 out of 557 specimens. The mutation types included V600E (n= 5) ,V600A (n= 2) ,V600M (n= 1) ,D594G (n= 1),G464E (n= 1),K601R (n= 2) and S605N (n= 1).KRAS mutation was detected in 6 cases including G12C (n= 3),G12A (n= 1),G12D (n=1) andG13D (n= 1).PIK3CA mutation was observed in 4 samples including E545G (n= 2) and H1047R (n= 2).Besides,NRAS mutation (Q61R) was detected in 1 case and MEK1 mutation (D61Y) was noted in 1 case. These gene mutations were not significantly correlated with the age, gender, smoking status and clinical staging of the patients. Univariate survival analysis demonstrated the median survival time of patients with gene mutation was (10.30±0. 751) months (95％CI:8. 829-11. 771 months),significantly shorter than (12.80±0. 543) months (95％CI:11. 736-13. 864 months) of their counterparts without gene mutation (P=0. 011). Conclusions BRAF/ KRAS and PIK3CA gene mutation is detected in a small proportion of SCLC patients. These gene mutations are not significantly correlated with the clinical characteristics. Univariate survival analysis demonstrates that negative these gene mutations are negatively correlated with the clinical prognosis of SCLC patients.

Molecular characterizations and possible treatment strategies for Epstein-Barr virus-as-sociated gastric cancer / 中国肿瘤临床

In 2014, The Cancer Genome Atlas (TCGA) classified gastric cancer into four types based on the genotype include EBV-infect-ed tumors, genomically stable tumors, chromosomally unstable tumors and MSI tumors, among which Epstein-Barr virus-associated gastric cancer (EBVaGC) is expected to be most suitable for immunotherapy because of its molecular characteristics, such as PD-L1/2 amplification or upregulation. Understanding the molecular characterizations of EBVaGC is very important in clinical practice. The re-ported molecular characteristics of EBVaGC include: PD-L1/2 upregulation, PIK3CA mutation, ARID1A mutation, DNA hypermethyl-ation, and rare mutation of TP53. Therefore, the possible therapeutic strategies for EBVaGC include the use of immune checkpoint in-hibitors, PI3K/AKT signaling pathway inhibitors, or antiviral therapy. This review summarizes the important molecular characterizations and possible treatment strategies for EBVaGC.

PIK3CA amplification and PTEN deletion in invasive B-cell lymphoma and their clinico-pathological significance / 中国肿瘤临床

Objective:To investigate the expression of PIK3CA and PTEN in PI3K/Akt/Mtor signaling pathway and its correlation with clinicopathological parameters in invasive B-cell lymphoma.Methods:A total of 235 invasive B-cell lymphoma cases enrolled in First Affliated Hospital of Xinjiang Medical University from January 2008 to December 2012,without any pre-operative treatment,were collected;those included 205 cases of diffuse large B-cell lymphoma(DLBCL),27 cases of Burkitt lymphoma(BL),and the remaining three cases were somewhere between DLBCL and BL,but could not be classified clearly.The expression of PIK3CA and PTEN genes was detected by fluo-rescence in situ hybridization.The relationship between PIK3CA and PTEN genes was analyzed statistically and extended to clinicopathological parameters and prognosis.Results:The positive rate of PIK3CA amplification in invasive B-cell lymphoma was 12.3%(29/235),and the positive rate of clinical stageⅠ-Ⅱ(8.6%,12/139)was much lower than that ofⅢ-Ⅳ(17.7%,17/96),with the difference being statistically significant (P=0.038).The deletion rate of PTEN in invasive B cell lymphoma was 13.6%(32/235),which was not correlated with other clinicopathological features.PIK3CA amplification was negatively correlated with PTEN deletion(P=0.046),and neither was found to be significantly associated with survival.Conclusions:PIK3CA amplification and PTEN deletion play a role in the development of invasive B-cell lymphoma,and the former is associated with late stage of the disease.

Expression of 3 markers and its correlation with prognosis of patients with non-small cell lung cancer / 国际检验医学杂志

Objective To investigate the expressions of ALCAM,IL-17RA and PIK3CA in patients with non-small cell lung cancer,and to investigate the correlation between the above-mentioned indexes and patients′ prognosis.Methods A total of 65 patients with non-small cell lung cancer admitted to the third People′s Hospital in Liaocheng City were selected and were served as study objects.Immunohistochemical staining(S-P) method was used to detect the expression of ALCAM,IL-17RA and PIK3CA in tissues to analyze the difference of expression between different pathological parameters.And 65 patients were followed up after the operation to compare the survival time of patients in the negative expression group and the positive expression group,and to analyze the correlation between ALCAM,IL-17RA and PIK3CA and the prognosis of the disease.Results Among the 65 cases of patients,47 cases were positive for ALCAM with the positive rate of 72.3%,34 cases were positive for IL-17RA with the positive rate of 52.3%;31 cases were positive for PIK3CA with the positive rate of 47.7%.There was significant difference in the expression of ALCAM,IL-17RA and PIK3CA in patients with different pathological types,TNM staging and lymph node metastasis(P0.05).The median survival time of patients with positive results of ALCAM,IL-17RA and PIK3CA were lower than those of negative group,and the differences were statistically significant(P<0.05).Conclusion The expression of ALCAM,IL-17RA and PIK3CA increased in non-small cell lung cancer tissues to remind the higher degree of malignancy and poor prognosis.

Correlation of KRAS and PIK3CA gene status between primary tumors and paired metastases in colorectal cancer / 临床与实验病理学杂志

Purpose To investigate the mutation status of KRAS and PIK3CA gene in colorectal cancer (CRC) primary lesions and corresponding liver metastasis and its clinical significance.Methods The gene mutations of KRAS and PIK3CA were detected in 58 cases of primary lesions of CRC and corresponding liver metastasis tissue by real-time PCR.Results The mutation rates of KRAS were 31.03％ (18/58) and 25.86％ (15/58) in primary lesions of CRC and corresponding liver metastasis tissue,respectively,in which G12D was most commonly detected.The mutation rates of PIK3CA were 8.62％ (5/58) and 10.34％ (6/58) respectively,in which the most common mutation site was E545K.Only one case carried simultaneously both mutations of KRAS (G12D) and PIK3CA (E545K).The mutation of KRAS and PIK3CA had a good consistency between primary lesions and liver metastasis.Univariate analysis showed that the mutation of KRAS was related to the primary lesion of tumor location,the quantity of metastasis and the types of tumor (P ＜ O.05),PIK3 CA mutation was associated with the synchronous/metachronous liver metastasis and the quantity of metastasis (P ＜ 0.05).Multivariate Cox regression analysis showed that synchronous/metachronous liver metastasis and the mutation of KRAS were influencing factors for prognosis of CRC.The overall survival of patients with CRC who had simultaneous liver metastases was longer than those with heterotopic liver metastases;the overall survival of KRAS wild-type mutant patients was longer than those of mutant patients (P ＜ 0.05).Conclusion The G12D site of KRAS gene has the highest mutation frequency in CRC,KRAS/PIK3CA mutation has a good consistency of the primary lesions of CRC and corresponding liver metastasis.Primary lesions can be as the source of molecular detection.To achieve individualized treatment,we need to reassess the genetic status of metastasis based on the choice of targeted therapy for precision medicine.

Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group. MATERIALS AND METHODS: Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString’s nCounter technology and mutational analysis was performed by direct DNA sequencing. Data describing the clinicopathological characteristics and clinical courses were retrospectively collected. RESULTS: Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations. CONCLUSION: In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.

A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma Who Have Acquired Resistance to EGFR–Tyrosine Kinase Inhibitors / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We examined the efficacy of poziotinib, a second-generation epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with activating EGFR mutations, who developed acquired resistance (AR) to EGFR-TKIs. MATERIALS AND METHODS: This single-arm phase II study included EGFR-mutant lung adenocarcinoma with AR to erlotinib or gefitinib based on the Jackman criteria. Patients received poziotinib 16 mg orally once daily in a 28-day cycle. The primary endpoint was progression-free survival (PFS). Prestudy tumor biopsies and blood samples were obtained to determine resistance mechanisms. RESULTS: Thirty-nine patients were treated. Tumor genotyping was determined in 37 patients; 19 EGFR T790M mutations and two PIK3CA mutations were detected in the prestudy tumors, and seven T790M mutations were detected in the plasma assay. Three (8%; 95% confidence interval [CI], 2 to 21) and 17 (44%; 95% CI, 28 to 60) patients had partial response and stable disease, respectively. The median PFS and overall survival were 2.7 months (95% CI, 1.8 to 3.7) and 15.0 months (95% CI, 9.5 to not estimable), respectively. A longer PFS was observed for patients without T790M or PIK3CA mutations in tumor or plasma compared to those with these mutations (5.5 months vs. 1.8 months, p=0.003). The most frequent grade 3 adverse events were rash (59%), mucosal inflammation (26%), and stomatitis (18%). Most patients required one (n=15) or two (n=15) dose reductions. CONCLUSION: Low activity of poziotinib was detected in patients with EGFR-mutant non-small cell lung cancer who developed AR to gefitinib or erlotinib, potentially because of severe-toxicityimposed dose limitation.

Study of PIK3CA gene mutation status in different clinicopathological characteristics of breast cancer / 国际检验医学杂志

Objective To detect the mutation status of PIK3CA genes in breast cancer and to analyze its relation with clinico‐pathological characteristics .Methods The paraffin tissue samples in 176 cases of breast cancer were selected and the tissue DNA was extracted ,exon9 and exon20 were amplified by ARMS‐PCR .The mutation status of PIK3CA genes were detected ,other tissue samples in 20 cases of mammary gland disease were taken as the negative control .Results Among 176 samples of breast cancer tis‐sues ,45 cases of mutation were found with the mutation rate of 25 .6% ,which was dominated by H1047R mutation rate of exon20 with the mutation rate of 26 .7% (12/45);There were statistical difference between ER (+ ) and ER(-) and between PR(+ ) and PR(-) ,but no statistical difference was found between HER (+ ) and HER(-);PIK3CA gene mutation had correlation with cancer histological grade ,but no obvious correlation with tumor size ,age and lymph node status .Conclusion PIK3CA gene muta‐tion is correlated with breast cancer hormone receptor (HR) expression and tumor progression ;the PIK3CA gene mutation detection has an important significance for guiding the formulation of clinical indiidualized treatment .

The correlation of PIK3CA gene mutation and the efficacy of anti-HER2 targeted therapy for breast cancer / 国际肿瘤学杂志

It has been shown that the PIK3CA mutation in HER2 positive breast cancer is up to 25%, and thus activates PI3K-Akt signaling pathway,promotes HER2 mediated tumor cell epithelial transformation, alters the intrinsic phenotype of HER2 overexpression breast cancer,and finally leads to resistance to anti HER2 targeted therapy.Some studies have shown that the PIK3CA gene mutation is associated with the efficacy of anti-HER2 targeted therapy.Therefore,real-time monitoring of PIK3CA gene mutation will promote indivi-dualized anti-HER2 targeted therapy.

Clinicopathological Significance of Elevated PIK3CA Expression in Gastric Cancer

PURPOSE: PIK3CA is often mutated in a variety of malignancies, including colon, gastric, ovary, breast, and brain tumors. We investigated PIK3CA expression in gastric cancer and explored the relationships between the PIK3CA expression level and clinicopathological features as well as survival of the patients. MATERIALS AND METHODS: We examined PIK3CA expression in a tissue microarray of 178 gastric adenocarcinomas by immunohisto-chemistry and reviewed patients' medical records. RESULTS: In our study, 112 of the 178 gastric cancer patients displayed positive PIK3CA expression. Overexpression of PIK3CA was correlated with low grade differentiation (P=0.001), frequent lymphatic invasion (P=0.032), and high T stage (P=0.040). Patients with positive PIK3CA staining were more likely to display worse overall survival rate than those with negative PIK3CA staining, as determined by Kaplan-Meier survival analysis with log-rank test (P=0.047) and a univariate analysis using the Cox proportional hazard model (hazard ratio=1.832, P=0.051). CONCLUSIONS: Elevated PIK3CA expression was significantly correlated with tumor invasiveness, tumor phenotypes, and poor patient survival.

Targeting the Phosphatidylinositol-3-kinase Pathway in Gastric Cancer: Can Omics Improve Outcomes? / 대한배뇨장애요실금학회지

Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed. In the following review we discuss PI3K signaling, previous preclinical and clinical investigations in gastric cancer, and discuss future strategies aimed at overcoming resistance and improving efficacy. Identification and refinement of molecular tumor subtypes, development of predictive biomarkers along, and rational drug combination strategies are key to capitalizing on the therapeutic potential of PI3K pathway directed therapies in gastric cancers.

Targeting the Phosphatidylinositol-3-kinase Pathway in Gastric Cancer: Can Omics Improve Outcomes? / 대한배뇨장애요실금학회지

Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed. In the following review we discuss PI3K signaling, previous preclinical and clinical investigations in gastric cancer, and discuss future strategies aimed at overcoming resistance and improving efficacy. Identification and refinement of molecular tumor subtypes, development of predictive biomarkers along, and rational drug combination strategies are key to capitalizing on the therapeutic potential of PI3K pathway directed therapies in gastric cancers.

Análisis molecular del cáncer de colon esporádico / Molecular analysis of sporadic colon cancer

Background: In Chile, colorectal cancer (CRC) is often diagnosed in late stages. Thus, surgical treatment must be complemented with chemotherapy. KRAS mutations and microsatellite instability have been detected in these tumors. However, the response to treatment in patients without KRAS mutations varies and requires a better understanding. Aim: To determine the frequency and distribution of somatic point mutations in KRAS, BRAF and PIK3CA genes and microsatellite instability status (MSI) in patients with colon cancer (CC). Material and Methods: A prospective observational study of patients undergoing surgery for colon cancer. Tumor-derived DNA was analyzed by polymerase chain reaction (PCR) for the most frequent mutations of KRAS, BRAF and PIK3CA. PCR was also used to analyze MSI. Results: Fifty-eight patients with sporadic CC were analyzed, 16 showed KRAS mutations (G12R, G12D, G12V, G13D) and out of the 42 patients that did not show any mutation, 10 had mutations in BRAF (V600E) and PIK3CA (E542K, E545D, E545K, Q546E, H1047R). BRAF mutations alone or in combination with PIK3CA mutations were observed in 27% of high MSI tumors and in 2% of tumors without instability (p < 0.049). A higher percentage of high MSI tumors were located in the right colon (p < 0.001), and showed BRAF mutation (p < 0.020). Conclusions: The highest percentage of high MSI and BRAF mutations was observed in the right colon. Therefore, this study suggests the presence of different molecular features between right and left colon tumors that should be considered when defining the therapeutic management.