Markers of adenocarcinoma characteristic of the site of origin: development of a diagnostic algorithm.
OBJECTIVE
Patients with metastatic adenocarcinoma of unknown origin are a common clinical problem. Knowledge of the primary site is important for their management, but histologically, such tumors appear similar. Better diagnostic markers are needed to enable the assignment of metastases to likely sites of origin on pathologic samples.


METHODS
Expression profiling of 27 candidate markers was done using tissue microarrays and immunohistochemistry. In the first (training) round, we studied 352 primary adenocarcinomas, from seven main sites (breast, colon, lung, ovary, pancreas, prostate and stomach) and their differential diagnoses. Data were analyzed in Microsoft Access and the Rosetta system, and used to develop a classification scheme. In the second (validation) round, we studied 100 primary adenocarcinomas and 30 paired metastases.


RESULTS
In the first round, we generated expression profiles for all 27 candidate markers in each of the seven main primary sites. Data analysis led to a simplified diagnostic panel and decision tree containing 10 markers only: CA125, CDX2, cytokeratins 7 and 20, estrogen receptor, gross cystic disease fluid protein 15, lysozyme, mesothelin, prostate-specific antigen, and thyroid transcription factor 1. Applying the panel and tree to the original data provided correct classification in 88%. The 10 markers and diagnostic algorithm were then tested in a second, independent, set of primary and metastatic tumors and again 88% were correctly classified.


CONCLUSIONS
This classification scheme should enable better prediction on biopsy material of the primary site in patients with metastatic adenocarcinoma of unknown origin, leading to improved management and therapy.
Dennis
Jayne L
JL
Cancer Research UK Centre for Oncology and Applied Pharmacology, Beatson Laboratories, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1BD, United Kingdom.
Hvidsten
Torgeir R
TR
Wit
Ernst C
EC
Komorowski
Jan
J
Bell
Alexandra K
AK
Downie
Ian
I
Mooney
Jacqueline
J
Verbeke
Caroline
C
Bellamy
Christopher
C
Keith
W Nicol
WN
Oien
Karin A
KA
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009382:Neoplasms, Unknown Primary / Q000175:diagnosis* / Q000473:pathology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor