耶魯大學(xué)癌癥中心的一個(gè)研究團(tuán)隊(duì)已經(jīng)證實(shí),,10-20%的被分類為雌激素受體(ER)陰性的乳腺癌其實(shí)是陽(yáng)性的。了解何時(shí)以及為什么乳腺癌可能被錯(cuò)誤的分類對(duì)診斷患有乳腺癌的婦女的治療和預(yù)后具有重要意義,。
其研究結(jié)果在線發(fā)表在6月28日的《Journal of Clinical Oncology》上,。
一名被診斷患有乳腺癌的婦女可以通過免疫組織化學(xué)(IHC)進(jìn)行測(cè)試,IHC是可檢測(cè)出癌組織中特定蛋白質(zhì)存在的一個(gè)過程,。那些ER檢測(cè)為陽(yáng)性的患者會(huì)被給予內(nèi)分泌治療,,如他莫昔芬、Letrazol或類似的藥物,。10-20%的被錯(cuò)誤的分類為ER陰性的癌癥患者,,可能會(huì)被給予缺乏療效的治療。
在耶魯大學(xué)醫(yī)學(xué)院病理學(xué)教授,,醫(yī)學(xué)博士David Rimm的領(lǐng)導(dǎo)下,,研究小組強(qiáng)調(diào)了IHC評(píng)估乳腺癌雌激素受體的局限性,并確定了標(biāo)準(zhǔn)的ER測(cè)量的新方法,。他們使用了一種結(jié)合一系列標(biāo)準(zhǔn)控件的熒光檢測(cè)技術(shù)來檢測(cè)雌激素受體,。研究小組報(bào)道說,這個(gè)更加敏感,、重復(fù)性好的方法發(fā)現(xiàn)了那些最初被稱為“陰性”但其實(shí)為“陽(yáng)性”的病例,。
Rimm說:“我們的研究表明,雌激素受體測(cè)定的常規(guī)方法可能會(huì)導(dǎo)致10-20%的假陰性率,,這可能會(huì)導(dǎo)致乳腺癌患者的治療不足,,并且由于不恰當(dāng)?shù)臏y(cè)試,,我們可能會(huì)錯(cuò)過利用我們最好的藥物之一(他莫昔芬)的機(jī)會(huì)。”
該測(cè)試已授權(quán)給康涅狄格州Branford的HistoRx公司,。該測(cè)定方法將會(huì)在臨床實(shí)驗(yàn)室改進(jìn)修正案認(rèn)證的實(shí)驗(yàn)室很快的應(yīng)用于患者,。第一個(gè)發(fā)布測(cè)試的實(shí)驗(yàn)室將是加利福尼亞州Carlsbad的Genoptix公司。
這項(xiàng)研究的其他作者包括Allison Welsh,,Sudha Kumar,,Peter Gershkovich和Malini Harigopal。(生物谷Bioon.com)
生物谷推薦原文出處:
Journal of Clinical Oncology DOI: 10.1200/JCO.2010.30.3552
Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure
y R. Peck, Agnieszka K. Witkiewicz, Chengbao Liu, Ginger A. Stringer, Alexander C. Klimowicz, Edward Pequignot, Boris Freydin, Thai H. Tran, Ning Yang, Anne L. Rosenberg, Jeffrey A. Hooke, Albert J. Kovatich, Marja T. Nevalainen, Craig D. Shriver, Terry Hyslop, Guido Sauter, David L. Rimm, Anthony M. Magliocco and Hallgeir Rui
Purpose To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy.
Patients and Methods Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays.
Results Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001).
Conclusion Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy.