Molecular differential diagnosis of renal carcinoma: from microscopes to microsatellites

In the last decade, specific chromosomal alterations have been associated with different tumor types. These aberrations were originally detected by karyotyping and then by more sophisticated cytogenetic analysis. A few karyotypic alterations can be directly linked to distinct malignancies, such as the Philadelphia chromosome in acute lymphoblastic leukemia, loss of distal chromosome 3p 14 in small-cell lung cancer, the loss of distal chromosome 11p13 in Wilms' tumor, and loss or rearrangement of the short arm of chromosome 3 in clear and chromophobe RCC. The relative specificity of the latter findings enabled investigators to diagnose an occult renal clear-cell carcinoma from a supraclavicular lymph node metastasis by analysis of G-banded metaphase chromosomes obtained from this mass. A similar report based also on cytogenetic findings was published earlier. Karyotypic changes, however, detect only gross alterations visible to an observer. With more refined diagnostic tools, such as microsatellite analysis, other, even smaller, well defined lesions can be analyzed. A summary of the known frequencies of chromosomal losses is given in Table 1. The combination of certain LOH patterns has shown great promise in the differential diagnosis of renal tumors. The transfer of molecular genetics from the laboratory to surgical pathology and other clinical departments is a meaningful event and a challenging task. Molecular pathology is certain to become important in the diagnosis of tumors with unclear histology. Diagnosis based widely upon staining techniques and determination of a patient's prognosis by staging and grading alone will be increasingly accompanied by molecular genetic methods. Pathology may be on the verge of the greatest change since the introduction of the microscope.