Diagnosis of carcinoma of unknown primary site with the aid of simple PCR tests: a single-center experience

This study was aimed to incorporate PCR testing in the determination of organ/tissue origin for cancers of unknown primary site (CUP). We developed a PCR panel consisting of 7 expression markers (CDX2, CDH17, SPB, UGRP, MAM, LPB, TG) and 2 genes frequently mutated in cancer (KRAS and BRAF). The expression tests were intentionally interpreted in a non-quantitative way, i.e. classified tumors either as positive or negative expressors. While applying these tests to 135 cancers belonging to 8 common types of adenocarcinomas (AdCa), we observed that this panel was capable to clearly discriminate between gastrointestinal vs. female reproductive tract vs. lung vs. thyroid tumors in 112 (83%) of cases and provided suggestive clues to correct diagnosis in 20 (15%) of instances. We further assessed the performance of this panel, coupled with the occasional use of 2 additional mutation tests (somatic: EGFR; germ-line: BRCA1), in the real diagnostic setting. The PCR analysis of 20 consecutive CUP with known IHC status turned out to be clinically useful in 19 (95%) cases, with 16 (80%) instances of resolving the existing controversy and 3 (15%) cases of providing valuable confirmation to suspected diagnosis. PCR testing of 20 consecutive CUP with unknown IHC status succeeded to establish tumor organ/tissue origin in 15 (75%) instances and provided suggestive clues to the diagnosis in 3 (15%) patients. We conclude that simple non-expensive laboratory-developed PCR assays may aid CUP diagnosis in a significant proportion of cases.