Tissue of Origin Test Evaluated in Patients with Cancer of Unknown Primary


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According to results of a study published in the Journal of Molecular Biomarkers and Diagnosis,1 the recently developed Tissue of Origin Test (Pathwork Diagnostics, Inc) aids in the diagnosis of challenging cancer cases such as those that are metastatic or that have a complex clinical history, particularly those with cancer of unknown primary. The test is a microarray-based gene expression array for determining the similarity of a tumor specimen to 15 known tumor tissue types.

In the study, the researchers retrospectively performed the Tissue of Origin Test on biopsy specimens from patients with cancer of unknown primary. Assay results were correlated with clinical and pathologic features and treatment results. The Tissue of Origin test provided predictions of the primary site in 96% of patients with cancer of unknown primary. Predictions were generally consistent with clinicopathologic features.

Site-specific Therapy

Cancer of unknown primary accounts for approximately 2% to 5% of all cancer diagnoses. Although several clinical subsets with specific treatment implications have been identified, the majority of patients receive “broad-spectrum,” empiric chemotherapy, which is only modestly effective, producing median survivals of 9 to 11 months.2-4

“As treatments improve for specific cancer types, it becomes more important to identify the tissue of origin in patients with cancer of unknown primary so that site-specific therapy can be administered,” explained lead researcher John D. Hainsworth, MD, Chief Scientific Officer, Sarah Cannon Research Institute, Nashville. “Accurate identification could allow these patients to benefit as treatments targeted for specific malignancies improve.”

Study Data

In the study, the Tissue of Origin test was successfully performed in 45 tumor specimens. In 43 of 45 assays (96%), a specific tissue of origin was predicted. The most commonly identified tissues of origin included lung (11), pancreas (6), sarcoma (6), ovary (5), and colon (4). Most diagnoses were compatible with the clinical features, immunohistochemical staining, and response to treatment.

The Tissue of Origin Test results were also correlated with previous cancer of unknown primary test results using a molecular 10-gene reverse transcriptase polymerase chain reaction cancer of unknown primary assay designed to detect six primary cancer sites. The Tissue of Origin test provided predictions in a higher percentage of patients than did the cancer of unknown primary assay (96% vs 53%). Agreement between the Tissue of Origin test and the cancer of unknown primary assay was relatively low, possibly related to the limited number of genes assessed by the cancer of unknown primary assay. ■

References

1. Hainsworth JD, Pillai R, Henner WD, et al: Molecular tumor profiling in the diagnosis of patients with carcinoma of unknown primary site: Retrospective evaluation of gene microarray assay. J Mol Biomark Diagn 2:106, 2011.

2. Hainsworth JD, Erland JB, Kulman LA, et al: Carcinoma of unknown primary site: Treatment with 1-hour paclitaxel, carboplatin, and extended schedule etoposide. J Clin Oncol 15:2385-2393, 1997.

3. Greco FA, Burris HA, Litchy S, et al: Gemcitabine, carboplatin, and paclitaxel for patients with carcinoma of unknown primary site: A Minnie Pearl Cancer Research Network study. J Clin Oncol 20:1651-1656, 2002.

4. Culine S, Lortholary A, Voigt JJ, et al: Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: Results of a randomized phase II study. J Clin Oncol 21:3479-3482, 2003.



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