Dennis-2005

Clinical settingCases of adenocarcinoma (or tumour types included in the differential diagnosis of adenocarcinoma) selected from the records of a single pathology department. Sample numbers of specific primary tumours were chose to reflect the frequency of presentation with metastatic disease, rather than their overall incidence.
Participants and Country352 primary tumour samples were included. 261 adenocarcinomas: 35 breast, 47 colon, 46 lung A validation set of 100 tumour samples and 30 paired metastases was used to test the diagnostic algorithm.
Study designCross sectional study
Target conditionThe target condition was identification of the primary tumour organ of origin. The reference standard diagnosis was taken from the original pathology records of the sample.
TestsThe expression profiles of 27 candidate markers were measured using tissue micro-arrays and immunohistochemistry. Data were analysed using the Rosetta program, to derive a decision tree to classify tumours based on their IHC profile. This analysis led to a smaller panel of 10 markers: CA125, CDX2, CK7, CK20, oestrogen receptor, PSA, GCDFP-15, lysozyme, mesothelin and TTF1. A decision tree was also included, which gives the a primary tumour classification algorithm based on these ten markers. Correct assignment of primary tumour site was obtained in 87% of primary and metastatic tumours using a diagnostic table, and 89% using the decision tree.
Follow upAll primary tumour diagnoses were known at the outset of the study.
Proportion with adenocarcinomaFor the training set 261/352 (74%)
Primary or metastatic tumour?The algorithm was developed using primary tumours, but tested with a validation set of 100 primary tumours and 30 paired metastases
Sample typeHistopathology
Notes

From: Guideline chapter 2, Diagnosis

Cover of Diagnosis and Management of Metastatic Malignant Disease of Unknown Primary Origin
Diagnosis and Management of Metastatic Malignant Disease of Unknown Primary Origin.
NICE Clinical Guidelines, No. 104.
National Collaborating Centre for Cancer (UK).
Copyright © 2010, National Collaborating Centre for Cancer.

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