Previstage™ GCC test for staging patients with colorectal cancer

被引:5
作者
Mejia, Alex [1 ]
Waldman, Scott A. [1 ]
机构
[1] Thomas Jefferson Univ, Dept Pharmacol & Expt Therapeut, Philadelphia, PA 19107 USA
基金
美国国家卫生研究院;
关键词
colorectal cancer; guanylyl cyclase C; lymph node; metastatic disease; predictive marker; prognostic marker; qRT-PCR; quantitative reverse transcriptase-polymerase chain reaction; staging;
D O I
10.1586/14737159.8.5.571
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
The presence of tumor cells in regional lymph nodes is the most important prognostic and predictive marker in staging patients with colorectal cancer. Cancer cells in lymph nodes are associated with a poorer prognosis and an increased risk of recurrent disease. Additionally, nodal metastases identify patients who derive maximum benefit from adjuvant therapy. However, traditional paradigms for staging patients with colorectal cancer underestimate the extent of metastases and patients whose lymph nodes are ostensibly free of tumor cells by histopathology (pN0) have a 25-30% risk of developing recurrent disease, reflected by the presence of occult nodal metastases. These observations underscore the unmet clinical need for molecular approaches to accurately detect metastatic disease and identify patients at risk for disease relapse that could benefit from adjuvant chemotherapy. Detection of disease-specific mRNA targets as prognostic and predictive markers employing quantitative reverse transcription (qRT)-PCR is an emerging technology that has become a benchmark for individualization of patient management. However, to date, applications of qRT-PCR to detecting occult nodal metastases in colorectal cancer have been equivocal, reflecting markers with suboptimal sensitivity and specificity; limitations of utilizing qualitative, rather than quantitative, RT-PCR; and underpowered study designs based on inadequate patient populations. In that context, guanylyl cyclase C (GCC) is the most sensitive and specific biomarker for metastatic colorectal cancer in extra-intestinal tissues. GCC qRT-PCR detects occult metastases in lymph nodes, providing the most powerful independent prognostic information for predicting disease recurrence in pNO patients in prospective multicenter clinical trials. This technology forms the basis for the Previstage (TM) GCC Colorectal Cancer Staging Test encompassing a proprietary multiplex qRT-PCR assay compatible with formalin-fixed, paraffin-embedded lymph nodes for detecting occult metastases. Previstage GCC is a new diagnostic tool that may improve the accuracy of staging, prognosis of clinical outcomes and prediction of therapeutic responses to adjuvant therapy, representing a key advance in the management of patients with colorectal cancer.
引用
收藏
页码:571 / 578
页数:8
相关论文
共 55 条
[31]   Improved tumor staging in colorectal cancer [J].
Lindblom, A .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (04) :264-265
[32]  
Lucas KA, 2000, PHARMACOL REV, V52, P375
[33]   Prognostic significance of the wnt signalling pathway molecules APC, β-catenin and E-cadherin in colorectal cancer -: a tissue microarray-based analysis [J].
Lugli, A. ;
Zlobec, I. ;
Minoo, P. ;
Baker, K. ;
Tornillo, L. ;
Terracciano, L. ;
Jass, J. R. .
HISTOPATHOLOGY, 2007, 50 (04) :453-464
[34]   Prognostic significance of occult metastases in colon cancer [J].
Merrie, AEH ;
van Rij, AM ;
Dennett, ER ;
Phillips, LV ;
Yun, K ;
McCall, JL .
DISEASES OF THE COLON & RECTUM, 2003, 46 (02) :221-231
[35]   Drug therapy - Systemic therapy for colorectal cancer [J].
Meyerhardt, JA ;
Mayer, RJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (05) :476-487
[36]   Quantitative real-time PCR: a powerful ally in cancer research [J].
Mocellin, S ;
Rossi, CR ;
Pilatil, P ;
Nitti, D ;
Marincola, FM .
TRENDS IN MOLECULAR MEDICINE, 2003, 9 (05) :189-195
[37]   Detection and prediction of micrometastasis in the lymph nodes of patients with pN0 gastric cancer [J].
Nakajo, A ;
Natsugoe, S ;
Ishigami, S ;
Matsumoto, M ;
Nakashima, S ;
Hokita, S ;
Baba, M ;
Takao, S ;
Aikou, T .
ANNALS OF SURGICAL ONCOLOGY, 2001, 8 (02) :158-162
[38]   Is occult lymph node disease in colorectal cancer patients clinically significant? A review of the relevant literature [J].
Nicastri, Daniel G. ;
Doucette, John T. ;
Godfrey, Tony E. ;
Hughes, Steven J. .
JOURNAL OF MOLECULAR DIAGNOSTICS, 2007, 9 (05) :563-571
[39]   Quantification of mRNA using real-time RT-PCR [J].
Nolan, Tania ;
Hands, Rebecca E. ;
Bustin, Stephen A. .
NATURE PROTOCOLS, 2006, 1 (03) :1559-1582
[40]   Comparative detection of lymph node micrometastases of stage II colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry [J].
Noura, S ;
Yamamoto, H ;
Ohnishi, T ;
Masuda, N ;
Matsumoto, T ;
Takayama, O ;
Fukunaga, H ;
Miyake, Y ;
Ikenaga, M ;
Ikeda, M ;
Sekimoto, M ;
Matsuura, N ;
Monden, M .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (20) :4232-4241