Retrospective analysis of gene expression profiling and TTF-1 staining in cancer of unknown primary (CUP).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10579-10579
Author(s):  
Wendy M. Chiang ◽  
Gary M. Strauss ◽  
J. Scott Nystrom
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Small Cell Lung Carcinoma ◽  
False Negative ◽  
False Negative Rate ◽  
Diagnostic Technique ◽  
Unknown Primary ◽  
Site Location ◽  
Cell Lung Carcinoma

10579 Background: CUP involves extensive use of immunohistochemical (IHC) stains because no individual marker is highly both site specific or sensitive. IHC algorithms lack standardization and may even eliminate actual primary sites. Extensive validation studies with gene expression profiling (GEP) has shown it be a new diagnostic technique that further contributes tumor site location in CUP. Thyroid transcription factor-1 (TTF-1) IHC stain is commonly used to identify the pulmonary origin of CUP (particularly adenocarcinoma) and is often used to exclude lung primary in CUP patients. This study evaluates the utility of TTF-1 staining in lung primaries (specifically non-small cell lung carcinoma - NSCLC) of CUP to GEP testing. Methods: This retrospective study contains data obtained from a registry of physicians who received the GEP-based Tissue of Origin (TOO) test (Pathwork Diagnostic, Sunnyvale, CA) between 07/2009 and 12/2009 on CUP cases. Sixty-six physicians contributed 111 TOO test cases. Only cases that had TTF-1 done were included for analysis and these were compared to TOO NSCLC results. Results: Out of 111 cases, there were 73 analyzable TTF-1 results with 12 cases of NSCLC and 61 cases of non-NSCLC by TOO (see TABLE). Assuming that the results of TOO testing accurately indicated the true primary site, the sensitivity and specificity of TTF-1 was 50% and 90%, respectively. The false negative rate was 50%, indicating that half of the identified NSCLC cases in this series had negative TTF-1. On the other hand, 10% of the 61 cases with primaries other than NSCLC (none of whom had thyroid cancer), had positive TTF-1. The “false positive” TTF-1 cases comprised 4 ovarian, 1 breast and 1 colorectal as the site of origin. Conclusions: TTF-1 has limited utility in identifying NSCLC in the setting of CUP. Half of NSCLCs identified by TOO testing had negative TTF-1, and 10% of non-lung primaries were TTF-1 positive. Negative TTF-1 should not be used to exclude NSCLC in the workup of CUP. [Table: see text]

scholarly journals Gene expression profiling and its use in adenocarcinomas of unknown primary origin: A case report

2015 ◽  
Vol 10 (4) ◽  
pp. 2657-2661
Author(s):  
ANA CEBOLLERO DE MIGUEL ◽  
ROBERTO PAZO CID ◽  
JAVIER MARTINEZ TRUFERO ◽  
ISABEL PAJARES BERNAD ◽  
LOURDES CALERA URQUIZU ◽  
...  
Keyword(s):  
Gene Expression ◽  
Case Report ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Unknown Primary ◽  
Primary Origin ◽  
Unknown Primary Origin

Identifying the primary site using gene expression profiling in patients with carcinoma of an unknown primary (CUP): a feasibility study from the GEFCAPI

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22168-e22168
Author(s):  
Y. Loriot ◽  
M. Gross-Goupil ◽  
T. Lesimple ◽  
E. Blot ◽  
Y. Merrouche ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Phase Iii ◽  
Unknown Primary ◽  
Primary Cancer ◽  
Recommended Treatment ◽  
Dismal Prognosis ◽  
Diagnostic Biopsy

e22168 Background: CUP are an heterogeneous family of neoplasms with a dismal prognosis, with empiric chemotherapy as the recommended treatment. The aim of this study was to evaluate the feasibility of a 500-mRNA microarray to identify the tissue of origin in patients with CUP. Methods: Diagnostic biopsy formalin-fixed, paraffin-embedded (FFPE) specimens from 22 patients with CUP were prospectively collected. Gene expression profiling was performed using oligonucleotide microarray that contains 495 genes selected as highly differentially expressed between 49 tumor types (CupPrint). Results: The assay was successfully performed on specimens from 18 of the 22 patients (82%). It could not be performed because of a low RNA preservation in the remaining 4 cases. The median age was 57 years (range: 29–70 years). The median delay from tissue shipping to receipt of CupPrint result was 11 days (range: 1–26 days). The most common tissues of origin identified were lung cancer (22%) and colorectal cancer (17%). Of note, a primary cancer which would not be adequately treated by an empiric chemotherapy regimen currently recommended in CUP (like cisplatin-gemcitabine or carboplatin-paclitaxel) was identified in about half patients: kidney cancer (1), hepatocarcinoma (1), colorectal cancer (3), head and neck cancer (2) and cholangiocarcinoma (1). Conclusions: Gene expression profiling of FFPE biopsy specimens from patients with CUP is feasible in a reasonable delay, making it feasible in clinical practice. A phase III randomized trial is planned to compare therapy based on gene expression-suspected primary cancer versus empiric chemotherapy. No significant financial relationships to disclose.

Estimation of expected survival time using gene expression profiling for tumor site origin.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10584-10584
Author(s):  
William David Henner ◽  
J. Scott Nystrom ◽  
John D. Hainsworth ◽  
Gauri R. Varadhachary ◽  
Frank A. Greco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Patient Survival ◽  
Unknown Primary ◽  
Cancer Type ◽  
Carcinoma Of Unknown Primary ◽  
Tissue Of Origin ◽  
The Relationship ◽  
Similarity Scores

10584 Background: Expected survival is an important factor in treatment selection and patient decision making. Gene expression profiling for tissue of origin (GEP TOO) can be used to classify metastatic and poorly-differentiated tumors according to the most likely primary site for difficult-to-diagnose tumors. The Pathwork Tissue of Origin Test, (Redwood City, CA) generates Similarity Scores (SS), one for each of the 15 tissues on the Tissue of Origin Test Panel and sum to 100. The highest SS has been validated as the most likely tissue of origin in a large validation study (Pillai et al. 2010). This abstract reports the relationship between the highest SS for a sample and patient survival. Methods: Two cohorts were analyzed in IRB-approved studies. Cohort 1 consisted of 45 patients with carcinoma of unknown primary treated empirically with therapy for carcinoma of unknown primary with known outcome data including survival. Cohort 2 consisted of 107 patients receiving the TOO test in routine clinical practice and included in a decision impact registry study. The relationship between the highest SS generated by the TOO test was examined using parametric (Gamma) and non-parametric (Cox Proportional Hazards) regression models with covariates of age, gender and median survival of the cancer type indicated. Logrank tests were performed to compare survival in patients with SS above or below 50 in each cohort. Results: The highest SS generated by the TOO Test was strongly and positively correlated with patient survival in both Cohort 1 (p = 0.0093, Cox PH) and in Cohort 2 (p=0.0045, Gamma). In Cohort 1, survival for patients with a SS < 50 was 5.9 mos and for patients with a SS ≥ 50 was 9.7 mos (p=0.03, logrank). In Cohort 2, survival for patients with a SS < 50 was 10.6 mos and 22.6 mos for patients with a SS ≥ 50 (p=0.0073, logrank). Conclusions: The Similarity Scores generated by GEP TOO Test have been validated as an aid to diagnosis for difficult-to-diagnose malignancies. Two independent studies of this GEP TOO Test demonstrated a strong positive relationship between the highest SS and survival. This has the potential to expand the clinical utility of this test beyond diagnosis to include prognosis. Further studies to examine this question are underway.

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