Biochemical assays for tumor-associated enzymes, hormones, and other tumor markers in the blood cannot be utilized for definitive diagnosis of cancer; however, they are used with varying success as screening tests and have utility in monitoring the response to therapy or detecting disease recurrence. The application of these assays is considered with many of the specific forms of neoplasia discussed in other chapters, so only a few examples suffice here. PSA, used to screen for prostatic adenocarcinoma, is one of the most frequently used tumor markers in clinical practice. Prostatic carcinoma can be suspected when elevated levels of PSA are found in the blood. However, PSA screening also highlights problems encountered with use of virtually every tumor marker. Although PSA levels often are elevated in cancer, PSA levels also may be elevated in benign prostatic hyperplasia (Chapter 18). Furthermore, there is no PSA level that ensures that a patient does not have prostate cancer. Thus, the PSA test suffers from both low sensitivity and low specificity, and its use as a screening tool has become quite controversial. The PSA assay is extremely valuable, however, for detecting residual disease or recurrence following treatment for prostate cancer. Other tumor markers used in clinical practice include carcinoembryonic antigen (CEA), which is elaborated by carcinomas of the colon, pancreas, stomach, and breast, and alpha fetoprotein (AFP), which is produced by hepatocellular carcinomas, yolk sac remnants in the gonads, and occasionally teratocarcinomas and embryonal cell carcinomas. Like PSA, CEA and AFP can be elevated in a variety of non-neoplastic conditions and thus also lack the specificity and sensitivity required for the early detection of cancers, but they may be useful in monitoring disease once the diagnosis is established. With successful resection of the tumor, these markers disappear from the serum; their reappearance almost always signifies recurrence. CEA is further discussed in Chapter 15 and alpha fetoprotein in Chapter 16.
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An increasing number of molecular techniques are being used for the diagnosis of tumors and for predicting their behavior.
Diagnosis of malignancy. Because each T cell and B cell has unique antigen receptor gene rearrangements, polymerase chain reaction (PCR)–based detection of rearranged T-cell receptor or immunoglobulin genes allows monoclonal (neoplastic) and polyclonal (reactive) proliferations to be distinguished. Many hematopoietic neoplasms, as well as a few solid tumors, are defined by particular translocations, so the diagnosis can be made by detection of such translocations. For example, fluorescence in situ hybridization (FISH) or PCR analysis (Chapter 7) can be used to detect translocations characteristic of Ewing sarcoma and several leukemias and lymphomas. PCR-based detection of BCR-ABL transcripts can confirm the diagnosis of chronic myeloid leukemia (Chapter 12). Finally, certain hematologic malignancies are now defined by the presence of point mutations in particular oncogenes. For example, as mentioned earlier, the diagnosis of another myeloid neoplasm called polycythemia vera requires the identification of specific mutations in JAK2, a gene that encodes a nonreceptor tyrosine kinase.