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.

CD49f Can Act as a Biomarker for Local or Distant Recurrence in Breast Cancer / 한국유방암학회지

PURPOSE: Metastasis and local recurrence are the primary causes of treatment failure and patient death in breast cancer. The aim of this study was to validate a metastasis- and local recurrenceassociated biomarker for prognostic evaluation and planning treatment strategies. METHODS: Formalin-fixed, paraffin-embedded tissues from a cohort of 312 patients (all stage II and III) were used. The prevalence of CD49f⁺ cells in the patients' tumors was analyzed and correlated with clinical characteristics to determine its prognostic and clinical implications. RESULTS: CD49f⁺ tumor cells were found in a minority of tumors, with 62.8% of the samples showing not a single cell of this subtype. In the clinical characteristics analysis, which were performed with t-tests, CD49f⁺ tumors were not associated with age, tumor size, World Health Organization grade, nodal status, human epidermal growth factor receptor 2 status, progesterone receptor status, or estrogen receptor status, although they were significantly associated with disease recurrence (distant metastasis or/and local recurrence). Univariate survival analysis using the Kaplan-Meier method showed that CD49f⁺ tumors were associated with markedly decreased disease-free survival (DFS); the same result was found using multivariate Cox analysis, even when only chemotherapy-treated patients were analyzed. CONCLUSION: Our results indicated that breast tumors with CD49f⁺ cancer cells are associated with an increased risk for disease recurrence after initial surgery with poor clinical outcomes (decreased DFS). Therefore, as it requires testing for only one additional protein, adding CD49f testing to conventional surgical pathology is a strategy that has great potential for prognostic and treatment-guidance purposes.

Comparative study of clinic and pathologic data of hepatitis B virus ralated membranous nephropathy between children and adult / 中国医师进修杂志

Objective To discuss the similarities and differences of clinical manifestation and pathological characteristics in hepatitis B virus related membranous nephropathy (HBV-MN) between children and adult. Methods Ninety cases with HBV-MN were divided into two groups according to the age:children group (33 cases) and adult group (57 cases). A retrospective control study was carried out to analyze the clinical and pathological features of the two groups. Results The incidence of anemia in children group was 45.45% ( 15/33 ), which was significantly higher than that in adult group [15.79% (9/57)](P ＜ 0.01). Nephrotic syndrome was the largest proportion in two groups,but there was no significant difference in the composition of clinical manifestations between two groups (P ＞0.05). Membranous nephropathy Ⅱ was common in pathological stage in two groups. The incidence of membranous nephropathy Ⅱ in children group was 63.64% (21/33),which was significantly higher than that in adult group [42.11%(24/57)] (P ＜ 0.05 );immunohistochemistry showed "all bright", and the deposition of HBcAg in renal biopsy was also higher than that in adult group (P ＜ 0.05). Conclusion There are some similarities and differences in HBV-MN between children and adult patients,and these will help to improve the levels of diagnosis and treatment.

Primary experimental results of methylseleninic acid on the proliferation inhibition and apoptotic induction in human high-metastatic large cell lung cancer cell line L9981 / 中国肺癌杂志

<p><b>BACKGROUND</b>It has been proved that selenium has remarkable effects in the prevention of cancer and proliferation inhibition for breast cancer and prostate cancer. Up to now, little is known, however, if methylseleninic acid (MSA) has the anticancer effect on lung cancer or not. The objective of this study is to detect the effect of MSA on proliferation inhibition and apoptotic induction for human high-metastatic large cell lung cancer cell line L9981, and to explore the molecular mechanisms.</p><p><b>METHODS</b>The changes of proliferation, clone formation, apoptotic level and cell cycles were detected in L9981 by trypan blue staining, clone formation suppression test, and flow cytometry before and after treating with different concentration of MSA. The expression level of proliferative-related and apoptotic-related genes was also determined in L9981 by flow cytometry.</p><p><b>RESULTS</b>(1)The proliferation ability of L9981 was remarkably inhibited at the concentration of 0.5μmol/L of MSA (P < 0.05), and the cells were arrested at G0/G1 phase after treating with the same concentration. (2)Apoptosis of L9981 was remarkably induced by MSA at the concentration of 2.5μmol/L (P < 0.05). (3)The clone formation ability of L9981 was significantly suppressed by MSA at the concentration of 5.0μmol/L (P < 0.05). (4)The expression levels of P53, P21, Fas, FasL and Bax were remarkably up-regulated after treatment with MSA.</p><p><b>CONCLUSIONS</b>(1)MSA can significantly suppress the proliferation and clone formation ability of human high-metastatic large cell lung cancer cell line L9981, and also induce apoptosis of L9981. (2)The anticancer effects of MSA might be related to regulate the expression of cell cycle-related genes and apoptotic-related genes in the human high-metastatic large cell lung cancer line L9981.</p>