BackgroundThe heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP’s prognostic accuracy in an independent cohort of cutaneous melanoma patients.MethodsThis multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival.ResultsThe 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively (P < 0.001). The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each). GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each).ConclusionsThe GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual’s risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4016-3) contains supplementary material, which is available to authorized users.
Background: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis.Objective: To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management.Methods: Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n = 586) were collected from 23 independent centers in a prospectively designed study. A GEP signature
Purpose: A clinical hurdle for dermatopathology is the accurate diagnosis of melanocytic neoplasms. While histopathologic assessment is frequently sufficient, high rates of diagnostic discordance are reported. The development and validation of a 35-gene expression profile (35-GEP) test that accurately differentiates benign and malignant pigmented lesions is described. Methods: Lesion samples were reviewed by at least three independent dermatopathologists and included in the study if 2/3 or 3/3 diagnoses were concordant. Diagnostic utility of 76 genes was assessed with quantitative RT-PCR; neural network modeling and cross-validation were utilized for diagnostic gene selection using 200 benign nevi and 216 melanomas for training. To reflect the complex biology of melanocytic neoplasia, the 35-GEP test was developed to include an intermediate-risk zone. Results: Validation of the 35-GEP was performed in an independent set of 273 benign and 230 malignant lesions. The test demonstrated 99.1% sensitivity, 94.3% specificity, 93.6% positive predictive value and 99.2% negative predictive value. 96.4% of cases received a differential result and 3.6% had intermediate-risk. Conclusions: The 35-GEP test was developed to refine diagnoses of melanocytic neoplasms by providing clinicians with an objective tool. A test with these accuracy metrics could alleviate uncertainty in difficult-to-diagnose lesions leading to decreased unnecessary procedures while appropriately identifying at-risk patients.
The pattern of immunohistochemical expression of cytokeratins 7 (CK 7) and 20 (CK 20) is commonly used to assess possible primary sites of metastatic carcinomas. Because pituitary tumors are almost always benign, there has been little interest in their cytokeratin profile. However, we recently reported the use of CK 7/20 expression to document malignant progression and metastasis of a pituitary tumor, indicating the potential diagnostic usefulness of the CK 7/20 profile of pituitary adenomas. We analyzed CK 7/20 expression in 97 pituitary adenomas subclassified by immunohistochemical hormone expression. In about 90% of all subtypes, CK 7 was either negative or reactive in only a few scattered cells. Corticotrophs and sparsely granulated growth hormone-positive adenomas were consistently CK 20 positive (and CK 7 negative) whereas all other subtypes were almost always CK 20 negative. This CK 20-positive, CK 7-negative profile is previously described consistently only in colonic adenocarcinomas. This study documents that subtypes of pituitary adenomas have different CK 7/20 profiles. Whereas this pattern is likely to have diagnostic usefulness in only rare adenomas, the presence of a unique CK signature in corticotrophs and sparsely granulated growth hormone-positive adenomas, subtypes particularly noted for invasive and aggressive behavior, merits further investigation.
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