Molecular pathology of tumor metastasis. II. Molecular staging and differential diagnosis.

Molecular Pathology of Tumor Metastasis With the development of non-invasive methods, diagnosis of metastasis from various solid malignancies has become a routine task for diagnostic pathology. However, the differential diagnosis between primary and metastatic cancers and the precise identification of various metastatic cancer types requires the coordinated use of various morphological (light- and electron microscopic-), immunological and molecular techniques. The detection of the lymphatic spread of the primary tumor may now based on the sentinel lymph node technology while the identification of the hematogenous progression may be based on the analysis of the peripheral blood and the bone marrow. More and more frequently these techniques employ highly sensitive immunological and molecular techniques. Accordingly, clinical staging is now confronted with the results of molecular staging, where the only techniques which are able to detect cancer cells are immunocytochemistry or nucleic acid-based methodology. Although several clinical studies have provided evidences for the impact of the immunocytochemistry-based identification of micrometastases on the survival of patients with various type of cancers, none of these methods have become part of standard diagnostic protocols. Although more sensitive molecular techniques are being introduced to identify micrometastasis, their clinical significance is yet unknown. Multicentric clinical trials are now warranted to establish the clinical impact of molecular staging in various cancer types. Without the integration of these methods into the prognostic/predictive pathological protocols it is difficult to envision significant improvement in the results of cancer therapy.