Pathology and genetic testing

By reporting on the possible existence of a hereditary cancer and recommending further genetic evaluation, the pathologist can help identify families with hereditary cancer. Currently, however, recognition of a case of hereditary cancer relies predominantly on clinical criteria, as common cancers show only a few specific pathologic features that suggest hereditary predisposition. Furthermore, clinical criteria alone often fail to identify mutant gene carriers. In contrast to genes that have a high penetrance for causing cancer, such as BRCA1, APC, RET, and the mismatch repair genes, identifying carriers of mutant genes having a lower penetrance (as is the case for the BRCA2 gene) is more difficult. Studies to identify markers for mutant germline cancer-predisposing genes will typically require studying archival tissue specimens, but germline genetic testing on archival samples for research purposes is complicated by the need for patient consent unless specimens are stripped of their patient identifiers. Pathologists contemplating such research should seek informed consent for genetic testing prior to archiving tissues. The need for consent has led to concerns that certain types of cancer research projects will no longer be feasible; if patient consent has not been obtained, however, institutional review board-approved protocols that facilitate obtaining patient clinical data while maintaining patient confidentiality can overcome this problem. As clinical genetic testing for hereditary cancer becomes part of clinical practice, there are many concerns about the quality of service at each step in the process. One of the most important requirements for quality is to ensure that the performance of a genetic test is always linked to adequate pretest and posttest genetic counseling. Reporting of genetic test results should be standardized and include information about the technique used to identify mutations, the sensitivity and specificity of the test in detecting such mutations, and the limitations of the test. The report should also contain recommendations for further action and information packets to assist in the interpretation of the test. Pathologists have expertise in the area of laboratory proficiency testing and can play an important role in the establishment of a national proficiency program to ensure a quality genetic testing process. Cancer 1997; 80:636-48. © 1997 American Cancer Society.