乳腺癌干細胞突變與腋窩淋巴結轉移的相關性

1、Correlation of Breast Cancer Axillary Lymph Node MetastasesWith Stem Cell Mutations乳腺癌干細胞突變與腋窩淋巴結轉移的相關性Background lIn stem cell theory, breast cancer stem and progenitor cells (BCSCs) are central to cancer proliferation, metastaticpotential,andoutcomemeasures. Breast cancer stemandprogenitor cells h

2、ave the capacity to initiate tumors, produce multipletumorcell lineages,andmaintain a continuous population of malignant stem cells through self-renewal.lPrevious research found no oncologic abnormalities in stem and progenitor cells in benign breast tissue; however, oncogenes in thePI3K/Akt signali

3、ngpathwaywere identified instemand progenitor cell populations in breast cancer.l乳腺癌干細胞和祖細胞 (BCSCs) 是癌癥增殖、轉移潛能及轉歸結局的中心因素。乳腺癌干細胞和祖細胞可分化產生多種腫瘤細胞系，并通過自我更新而維持惡性干細胞群的延續(xù)。 l在乳腺癌干細胞和祖細胞群中發(fā)現(xiàn) PI3K/Akt 通路涉及到細胞增殖、信號傳導、轉移潛能等功能，也是目前乳腺癌臨床試驗青睞的化療靶點。Purpose lMutations in oncogenes AKT1, HRAS, and PIK3CA in breast ca

4、ncers result in abnormal PI3K/Akt signaling and tumor proliferation. They occur in ductal carcinoma in situ,in breast cancers, and in breast cancer stem and progenitor cells (BCSCs).lTo determine if variability in clinical presentation at diagnosis correlates withPI3K/Akt mutations in BCSCs and prov

5、ides an early prognostic indicator of increasedprogression and metastatic potential.l在乳腺癌中，癌基因 AKT1、HRAS、PIK3CA 的突變會導致PI3K/Akt 信號通路傳導異常和腫瘤異常增殖。這種現(xiàn)象常見于浸潤性導管癌以及乳腺癌干細胞及祖細胞 （BCSCs）中。 l本實驗主要研究乳腺癌干細胞（BCSCs）中 PI3K/Akt 信號通路的突變與乳腺癌的不同臨床表現(xiàn)之間的相關性，為判斷疾病加速進展和潛在轉移提供早期的預后指標。 MethodslWomenwithinvasiveduc-tal carcin

6、oma of the breast exceeding 1.0 cm were identified at tumor board meetings and enrolled in the study. Solid-tissuebreastspecimenswerecollectedatthetimeofmastec-tomy or lumpectomy before any adjuvant treatment.lSpecimens were obtained directly from the operating room andevaluated by a pathologist, an

7、d approximately1gof tumor tissuewas immediately transferred to the laboratory for processinginmammaryepithelial cellspecificmediuml研究對象為30例浸潤性導管癌的患者（IA 至 IIIB 期），腫瘤直徑1cm，術前未行任何輔助治療。l用流式細胞儀分離并收集乳房切除術或乳房腫瘤切除術中的惡性（BCSCs）和良性干細胞，并檢測癌基因突變情況。MethodslFollowing tissue analysis, medical records were reviewed,

8、and additional datawere compiled retrospectively foreach patient. Data collected included patient age at diagnosis,race/ethnicity, tumorhormonereceptor status,ERBB2(formerlyHER2/Neu) status, tumor histologic grade, pathologictumor stage, and condition at the last follow-upcontactl研究的主要目標為探討乳腺癌干細胞（BC

9、SCs）癌基因（ AKT1、HRAS 、 PIK3CA）的突變情況與腫瘤臨床特征的相關性，以及跟蹤隨訪該30例患者乳腺癌干細胞的突變與疾病進展的相關性。 Tumor Characteristics by PatientResultlAmong 30 tumors,10 tumors(33%) had BCSCs with AKT1,HRAS,orPIK3CA mutations,8of which have been previously reported.l The mean follow-up time was 22 monthsafterdiagnosis.Onepatientwaslo

10、sttofollow-upcon-tact. Twopatients died of disease, and 1 patient has brain metastases.No patients with BCSCs without mutations have evidence ofdisease.l11例（33%）患者有乳腺癌干細胞癌基因的突變。l該研究中位隨訪時間為22個月，有一位患者失聯(lián)。11例突變的患者中2位死于該疾病，有1位出現(xiàn)腦轉移。未檢測到癌基因突變的患者未報到疾病進展。 乳腺癌干細胞的突變情況與腫瘤臨床特征的相關性分析腋窩淋巴結轉移與乳腺癌干細胞突變的相關性 ConclusionlPatients with tumors in which BCSCs have a genetic abnormality of the PI3K/Akt signaling pathway are significantlymore likely to have lymph node metastases.lWhile axillary lymph node metastases are known to correlate with tumor size, BCSC mutation in this study was an independent predic