***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Breast cancer is the most common malignancy in United States women , accounting for > 40,000 deaths each year . These breast tumors are comprised of phenotypically diverse population s of breast cancer cells . Using a model in which human breast cancer cells were grown in immunocompromised mice , we found that only a minority of breast cancer cells had the ability to form new tumors . We were able to distinguish the tumorigenic ( tumor initiating ) from the nontumorigenic cancer cells based on cell surface marker expression . We prospect ively identified and isolated the tumorigenic cells as CD44+CD24−/lowLineage− in eight of nine patients . As few as 100 cells with this phenotype were able to form tumors in mice , whereas tens of thous and s of cells with alternate phenotypes failed to form tumors . The tumorigenic sub population could be serially passaged : each time cells within this population generated new tumors containing additional CD44+CD24−/lowLineage− tumorigenic cells as well as the phenotypically diverse mixed population s of nontumorigenic cells present in the initial tumor . The ability to prospect ively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival . Furthermore , because these cells drive tumor development , strategies design ed to target this population may lead to more effective therapies The cancer stem cell ( CSC ) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties . Although the existence of CSCs in human leukaemia is established , little evidence exists for CSCs in solid tumours , except for breast cancer . Recently , we prospect ively isolated a CD133 + cell sub population from human brain tumours that exhibited stem cell properties in vitro . However , the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour . Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo . Only the CD133 + brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID ( non-obese diabetic , severe combined immunodeficient ) mouse brains . Injection of as few as 100 CD133 + cells produced a tumour that could be serially transplanted and was a phenocopy of the patient 's original tumour , whereas injection of 105 CD133- cells engrafted but did not cause a tumour . Thus , the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis , giving strong support for the CSC hypothesis as the basis for many solid tumours , and establishes a previously unidentified cellular target for more effective cancer therapies PURPOSE This study evaluates the clinical significance of detection of carcinoembryonic antigen ( CEA ) mRNA in the dissected lymph nodes and peripheral blood sample s of patients with gastrointestinal or breast carcinomas . PATIENTS AND METHODS A total of 406 lymph nodes obtained from 65 patients were analyzed by both histologic and molecular examination of CEA-specific reverse transcriptase-polymerase chain reaction ( RT-PCR ) .  Peripheral blood sample s from another 102 patients were also analyzed by CEA-specific RT-PCR . Patients were followed up prospect ively for 24 + /- 12 months . RESULTS Of 406 lymph nodes , the positive detection rate increased from 20 % by histologic examination to 60 % by RT-PCR examination . The recurrence rate was 40 % in 15 cases showing positive results in both examinations , 14 % in 29 cases showing histologically negative but RT-PCR positive results , and none in 21 cases showing negative results in both examinations . The positive detection rate for CEA mRNA in peripheral blood sample s increased with advancing stage of disease . With respect to 62 curatively operated cases , CEA mRNA was detected in 12 cases . Four of these 12 cases developed metastatic disease after surgery whereas none of 50 cases negative by RT-PCR developed metastasis . CONCLUSION It has been shown that RT-PCR is a powerful tool to detect CEA mRNA in the lymph nodes or the peripheral blood . This is potentially very useful to determine high-risk patients for metastasis . Serial analysis is warranted to assess the long-term significance of this method and its therapeutic and prognostic implication Summary The clinical significance of detecting supposed tumour cell-derived mRNA transcripts in blood using the polymerase chain reaction ( PCR ) remains unclear . We have used a fully quantitative 5′-nuclease RT-PCR assay to screen for the expression of cytokeratins ( ck ) 19 and 20 and guanylyl cyclase C ( GCC ) in the peripheral blood of 21 healthy controls and 27 colorectal cancer patients .  Expression of cytokeratin 19 and 20 mRNA was detected in 30 % and 100 % of sample s , respectively , taken from healthy volunteers . There was no apparent difference in ck19 and ck20 mRNA transcription levels between controls and patients , or between patients with different Dukes ’ stages . While GCC mRNA was detected in only 1/21 control sample s , it was expressed in approximately 80 % of patients , although again there was no correlation between GCC levels and disease stage . Transcription levels of all three markers varied considerably between sample s , even between sample s taken from the same person at different times . We conclude that neither ck19 nor ck20 are reliable markers for the detection of colon epithelial cells in peripheral blood and that an evaluation of the usefulness of GCC awaits further longitudinal studies Abstract Background : Cytokeratins are predominantly expressed in epithelial cells and their malignant counterparts . Ultrasensitive methods for cytokeratin messenger RNAs ( mRNAs ) can detect rare circulating tumor cells consistent with hematogenous dissemination in epithelial-derived malignancies , including breast carcinomas . Intraoperative tumor-cell shedding may contribute to this process ; this hypothesis is based on the assumption that only tumor cells can be mobilized during surgical manipulation . Methods and Results : The present study addresses this issue by using cytokeratin 19 mRNA detection by reverse transcription-polymerase chain reaction ( RT-PCR ) in preoperative and postoperative blood sample s from 54 patients undergoing excisional biopsy for benign breast disease ; 22 healthy volunteers represented the control group . No cytokeratin RT-PCR positivity was found in the control or preoperative sample s. Cytokeratin RT-PCR positivity was found in 21 postoperative sample s ( 39 % ) . Conclusions : This finding shows that benign epithelial cells can be mobilized during breast surgery ; this effect of surgical manipulation warrants caution in the interpretation of RT-PCR positivity for cytokeratin mRNA in the peripheral blood of patients undergoing surgery for breast cancer Adjuvant chemotherapy is not routinely recommended in patients with colorectal cancer stage UICC II . Some of these patients , however , develop recurrent disease . Therefore , valid prognostic criteria are needed to identify high-risk patients who might benefit from adjuvant therapy . Disseminated tumor cells , detected in blood and bone marrow , may prove to be a valid marker , however , the prognostic relevance of these cells remains debated . In our study , we examined the prognostic significance of disseminated tumor cells in blood and bone marrow of patients with stage II colorectal cancer . Ninety patients with potentially curative ( R0 ) resection of colorectal cancer stage II were prospect ively enrolled into the study . Bone marrow and blood sample s were examined for disseminated tumor cells by CK 20 RT-PCR . Patient , tumor and treatment factors were analyzed as prognostic factors . Multivariate analysis confirmed tumor cell detection in blood ( hazard ratio 2.1 , p = 0.03 ) and T-category ( hazard ratio 2.2 , p = 0.02 ) to be independent prognostic factors for relapse-free survival . Tumor cell detection in postoperative blood sample s ( hazard ratio 7.7 , p < 0.001 ) and number of removed lymph nodes ( hazard ratio 6.4 , p < 0.001 ) were independent prognostic factors for disease-specific survival . Detection of circulating tumor cells in blood sample s of patients with stage II colorectal cancer identifies patients with poor outcome . This finding should be confirmed by further studies and could then be used as a basis for conducting a r and omized trial evaluating the effect of adjuvant chemotherapy in stage II patients Objective To evaluate the clinical relevance of real-time quantitative polymerase chain reaction ( qPCR ) detection of CEA and CK20 transcripts , as potentially related to tumor cell dissemination , in blood and peritoneal lavage from patients undergoing surgery for colorectal cancer . Summary Background Data Dissemination of single colorectal cancer cells in the peritoneal cavity , as well as in tumor drainage and peripheral blood vessels , might play a role in the metastasis process , thus affecting the clinical course . However , this phenomenon needs further elucidation . Methods In a prospect i ve study the authors evaluated the potential of qPCR in the detection of CEA and /or CK20 transcripts in the peritoneal lavage fluid and in the peripheral and mesenteric venous blood of 39 patients undergoing curative resection for colorectal cancer .  Peritoneal lavage and peripheral blood was sample d before and after tumor resection ; mesenteric venous blood was sample d from the major tumor-draining vein immediately before clamping . After RNA extraction and reverse transcription , qPCR was performed using specific cDNA primers and probes for CEA and CK20 . The dichotomous results from the qPCR were used as a predictor along with other covariates in Cox proportional hazard regression models of long-term outcome ( disease-free survival and overall survival ) . Results Of 39 patients , 11 were positive . The median follow-up at analysis was 31 months for all patients . The dichotomous qPCR covariate was significant , with P = .001 and .0035 for disease-free survival and overall survival , respectively , in the proportional hazard regression models with only qPCR . In seven patients , disseminated colorectal cancer cells were found in the peritoneal lavage fluid but not in blood specimens ; five of these patients ( 71 % ) had recurrence . Conclusions These data suggest that detection of mRNA coding for CEA and /or CK20 using qPCR has potential clinical utility as a prognostic marker and should be evaluated in larger clinical studies . Identification of patients at high risk for metastatic disease after curative resection of colorectal cancer might be improved by analyzing peritoneal lavage specimens in addition to blood sample s. This is based on the observation that in more than half of qPCR-positive patients , disseminated colorectal cancer cells were detected in peritoneal lavage specimens but not in blood sample s , and that 71 % of them had recurrence PURPOSE Approximately 30 % of patients with American Joint Committee on Cancer stage I or II colorectal cancer ( CRC ) develop systemic disease . We hypothesized that multimarker reverse transcriptase-polymerase chain reaction ( RT-PCR ) analysis of sentinel lymph nodes ( SNs ) draining a primary CRC could detect micrometastases not detected by conventional histopathologic analysis . PATIENTS AND METHODS In a multi-institutional study , 40 patients with primary CRC underwent dye-directed lymphatic mapping at the time of colon resection .  Each dye-stained SN was tagged , and the tumor and regional nodes were resected en bloc . All lymph nodes were examined by conventional hematoxylin and eosin ( HE ) staining . In addition , each SN was cut into multiple sections for cytokeratin immunohistochemical ( CK-IHC ) staining and for RT-PCR and electrochemiluminescent detection of three markers : beta-chain human chorionic gonadotropin , hepatocyte growth factor receptor , and universal melanoma-associated antigen . Whenever possible , RT-PCR assay was also performed on primary tumor tissue . The detection sensitivity of individual markers was 10(-3 ) to 10(-4 ) microg of RNA and one to five tumor cells in 10(7 ) lymphocytes of healthy donors . RESULTS One to three SNs were identified in each patient . An average of 15 nodes were removed from each CRC specimen . No nonsentinel ( untagged ) node contained evidence of tumor if all tagged ( sentinel ) nodes in the same specimen were histopathology tumor-negative . HE staining of SNs identified tumor in 10 patients ( 25 % ) , and CK-IHC of SNs identified occult micrometastases in four patients ( 10 % ) whose SNs were negative by HE . Of the remaining 26 patients with no evidence of SN involvement by HE or CK-IHC , 12 ( 46 % ) had positive RT-PCR results . The number of markers expressed in each SN correlated ( P < .04 ) with the T stage of the primary tumor . There was 79 % concordance in marker expression for the respective pairs ( n = 38 ) of primary tumor and histopathologically positive SNs , and 86 % ( 12 of 14 ) concordance between RT-PCR positive and histopathologically positive SNs . CONCLUSION Identification and focused examination of the SN is a novel method of staging CRC . CK-IHC and RT-PCR identified occult micrometastases in 53 % of patients whose SNs were negative by conventional st 
    Output:
    
CONCLUSION Quantification of CTCs in peripheral blood holds promise in predicting stage and outcome in colorectal cancer patients .
At present , evidence from the literature is too scarce to integrate quantitative RT-PCR assays to detect CTCs into the management of colorectal cancer