207- Detection capability: 0.01 % (mutant/total DNA) 1–4 (i.e. ≥1 mutant DNA
molecule in 10,000 wild type DNA molecules) - Turnaround time 2–4 days
- Available for analysis of 130 different mutations in >15 different cancer genes
Diagnosis of Cancer of an Unknown Primary
Metastatic cancer of unknown primary site (CUP) accounts for ~3 % of all malig-
nant neoplasms and is therefore one of the 10 most frequent cancer diagnoses in
humans. Patients with CUP present with metastatic disease for which the site of
origin cannot be identifi ed at the time of diagnosis. It is now accepted that CUP
represents a heterogeneous group of malignancies that share a unique clinical
behavior and, presumably, unique biology. Extensive work-up with specifi c pathol-
ogy investigations (immunohistochemistry, electron microscopy, molecular diagno-
sis) and modern imaging technology (CT, mammography, PET scan) have resulted
in some improvements in diagnosis, but the primary site remains unknown in most
patients. The most frequently detected primaries are carcinomas hidden in the lung
or pancreas. Several favorable sub-sets of CUP have been identifi ed, which are
responsive to systemic chemotherapy and/or locoregional treatment. Identifi cation
and treatment of these patients is important. The considered responsive sub-sets to
platinum-based chemotherapy are the poorly differentiated carcinomas involving
the mediastinal-retroperitoneal nodes, the peritoneal papillary serous adenocarcino-
matosis in females and the poorly differentiated neuroendocrine carcinomas. Other
tumors successfully managed by locoregional treatment with surgery and/or irradia-
tion are the metastatic adenocarcinoma of isolated axillary nodes, metastatic squa-
mous cell carcinoma of cervical nodes, or any other single metastatic site. Diagnosis
of CUP is important for personalized management of cancer. Diagnostics are being
developed for CUP using microarrays and gene expression analysis.
Diagnostics for Detection of Minimal Residual Disease
In the pre-molecular diagnostic era, hematologists used the microscope to identify
a complete remission of leukemia after treatment with chemotherapy. In a hemato-
logic complete remission, it is known that a large portion of the leukemic cells
remain out of sight. These cells, invisible to the microscopist, are the components of
an important clinical problem termed “minimal residual disease (MRD)”. RT-PCR
has been used to detect BCR-ABL transcripts in chronic myeloid leukemia (CML)
in the chronic phase. BCR-ABL transcripts were measured in blood samples of
patients in remission following treatment with imatinib using RT-PCR with BCR as
a control gene, thus ensuring standardization of the method in the participating lab-
oratories. There is a progressive reduction of the leukemic mass that exists below
Impact of Molecular Diagnostics on the Management of Cancer