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Purpose@#PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC).Previous studies have indicated an association between concomitant PIK3CA/TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and predictive roles of this co-mutation. @*Methods@#We retrospectively analyzed patients who were diagnosed with BC at Guangdong Provincial People’s Hospital (GDPH) who underwent next-generation sequencing. The correlation of concomitant PIK3CA/TP53 mutations with clinicopathological and mutational characteristics, and neoadjuvant systemic therapy (NST) responses was analyzed. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was used to verify associations between concurrent mutations and survival outcomes. @*Results@#In the GDPH cohort, concomitant PIK3CA/TP53 mutations were associated with more aggressive phenotypes, including human epidermal growth factor receptor 2 positive status, hormone receptor negative status, high Ki-67 expression, high histological grade, advanced TNM stage, and additional genetic alterations. Co-mutations also portended a worse response to NST, especially taxane-containing regimens, when compared with the TP53 mutant alone (odds ratio, 3.767; 95% confidence interval, 1.205–13.087; p = 0.028). A significant association was observed between concomitant PIK3CA/TP53 mutations and poor survival outcomes in the METABRIC cohort. @*Conclusion@#Concomitant PIK3CA/TP53 mutations not only suggested unfavorable features and poor prognosis in BC but also conferred less benefit to NST than TP53 mutations alone.
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Objective To explore expression level of circulating microRNA (miR)-133a and Galectin-3 and their potential clinical application in differential diagnosis between patients with chronic Keshan disease and dilated cardiomyopathy.Methods Twenty-eight patients with chronic Keshan disease and 28 cases of age-and sex-matched healthy people as control from the same severe historical endemic areas of Keshan disease in Heilongjiang Province,and another 28 patients with dilated cardiomyopathy from non-affected areas were chosen for the study.All the subjects were asked for disease history and did physical examination,examined by Doppler echocardiography for left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD),and collected fasting venous blood specimen (elbow vein).The plasma miR-133a and the serum Galectin-3 were determined by Real-time PCR and enzyme-linked immunosorbent method,respectively.Meanwhile,the correlation was analyzed between miR-133a,galectin-3,LVEF and LVEDD.Results The miR-133a and Galectin-3 levels in different groups were statistically different (F =48.789,9.485,P ＜ 0.01).The plasma miR-133a level in chronic Keshan disease group and dilated cardiomyopathy group [median (quartile):0.394 (0.271,0.770),1.665 (0.943,2.713)] were both significantly lower than those in control group [2.382 (1.502,3.302],P ＜ 0.01 or ＜ 0.05],and the plasma miR-133a level in chronic Keshan disease group was lower than that in dilated cardiomyopathy group (P ＜ 0.01).There was no significant difference of serum Galectin-3 level between chronic Keshan disease group and dilated cardiomyopathy group [17.710 (9.624,27.799),12.692 (9.376,26.290) μg/L,P ＞ 0.05],but both were significantly higher than those in control group [8.070 (7.135,9.308) μg/L,P ＜ 0.01].The miR-133a was positively correlated with LVEF (rs =0.297,P ＜ 0.01),while negatively correlated with LVEDD,and Galectin-3 (rs =-0.271,-0.318,P ＜ 0.05 or ＜ 0.01);the serum Galectin-3 was negatively correlated with LVEF (rs =-0.392,P ＜ 0.01),and positively correlated with LVEDD (rs =0.385,P ＜ 0.01).Conclusion The combined application of miR-133a,Galectin-3,LVEF and LVEDD may provide assistance in clinical differential diagnosis of chronic Keshan disease and dilated cardiomyopathy.
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<p><b>OBJECTIVE</b>To study the incidence of implantation metastasis of breast cancer in vacuum-assisted breast biopsy (VABB) needle tract in Chinese patients and evaluate the effect of neoadjuvant chemotherapy on needle tract metastasis following VABB.</p><p><b>METHODS</b>The breast cancer patients with established diagnosis by VABB were divided into two groups to receive open surgery or neoadjuvant chemotherapy prior to open surgery. The incidence of needle tract metastasis, disease-free survival (DFS) and overall survival (OS) were compared between the two groups.</p><p><b>RESULTS</b>A total of 214 patients were enrolled, among whom 94 directly underwent surgeries and 120 had neoadjuvant chemotherapy before surgery. The two groups showed no significant differences in the incidence of needle tract metastasis (3.2% vs 0.8%, P=0.206), DFS (P=0.221), or OS (P=0.531).</p><p><b>CONCLUSION</b>The incidence of needle tract metastasis is low after VABB, and neoadjuvant chemotherapy does not increase this risk.</p>
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Female , Humans , Biopsy, Needle , Methods , Breast , Breast Neoplasms , Pathology , Disease-Free Survival , Incidence , Needles , Neoadjuvant Therapy , Neoplasms, Second Primary , Drug Therapy , VacuumABSTRACT
<p><b>BACKGROUND</b>The epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) is playing an important role in the treatment of non-small cell lung cancer.The acquired resistance of EGFR-TKI has become a hot spot.This study aims to investigate VEGF-D expression level in lung adenocarcinoma with or without acquired resistance to gefitinib and in normal lung,so as to explore the role of VEGF-D in resistance of gefitinib.</p><p><b>METHODS</b>Lung adenocarcinoma,normal lung tissues adjacent to the carcinoma and adenocarcinoma with acquired resistance to gefitinib including some metastastic lymph nodes were obtained during operation.SYBR Green real-time PCR with beta actin gene as the endogenous control was performed to examine VEGF-D gene expression semi-quantitatively.After positive expression of VEGF-D was determined,the expression ratio and level in each group was analyzed qualitatively and quantitatively.</p><p><b>RESULTS</b>Exact significance was computed to compare VEGF-D expression ratios in groups of lung adenocarcinoma with acquired resistance to gefitinib(1/6,16.7%),lung adenocarcinoma(7/14,50.0%) and normal lung(16/16,100.0%) and the difference was significant(P=0.000 091 7).VEGF-D relative expression level in the seven lung adenocarcinoma cases was significantly lower than its corresponding normal lung tissue by analysis of nonparametric test(P < 0.01).</p><p><b>CONCLUSIONS</b>VEGF-D has a high-level expression in normal lung tissues,while has a decreased expression in lung adenocarcinoma with or without acquired resistance to gefitinib,suggesting that VEGF-D functions in lung adenocarcinoma with or without acquired resistance to gefitinib in a way,which is different from in normal lung.</p>