Tissue biopsies from body sites (e.g., breast, liver, kidney, lymph nodes, skin, bone, muscle, lung, bladder, prostate, thyroid, cervix) may be examined for the presence of benign, toxic, or malignant cells and conditions. The amount of tissue obtained and submitted to the laboratory depends on the specimen site and disease process (e.g., in liver biopsy, at least two to three liver cores >2 cm in length). These procedures may be performed in outpatient or inpatient settings. Some specimens should be collected early in the day. For ultrasound-guided prostate specimens (i.e., transrectal ultrasound), 6–12 threadlike sections of tissue are obtained, ranging from 0.5 to 1.5 cm in length. Pain and bloody urine are common afterward. Depending on the body site sampled, anesthetic agent (i.e., local or general) or conscious sedation and analgesia may be indicated.
Tissue obtained for routine histologic and pathologic examination requires special handling (e.g., place in 10% formalin or send fresh and intact). Tissue needed for frozen-section examination must be delivered to the laboratory immediately with no fixative added. Tissue needed for special studies (e.g., special stains for microorganisms, hormonal studies, DNA ploidy, bone biopsies) may need special handling. A frozen section is done upon the pathologist’s recommendation. In some cases, tissue freezing (frozen section) may be contraindicated because it is not in the patient’s best interest. Contact your individual laboratory for specific instructions.
After the biopsy, specimen is sent to the laboratory, various tests are done to identify the unique characteristics of the patient’s tumor cells and to select correct chemotherapy based on resistance to specific drugs. Multiple and complex genetic changes result from loss of control over normal cell growth, and these alterations may influence the tumor’s response to chemotherapy. To measure these changes, four major testing groups are used and include the following:
Extreme drug resistance assay tests solid tumors and malignant fluids (blood, bone marrow effusions), which determine the probability of a tumor’s resistance to specific chemotherapeutic drugs. If the tumor cells grow in the presence of extreme exposures to a specific drug, this indicates the presence of significant drug resistance and, by identifying inactive agents, avoids exposing patients to the toxicity of drugs that are likely to be ineffective, saves valuable treatment time, and decreases the possibility of cross-resistance to other effective agents.
Differential staining cytotoxicity assay uses special stains and techniques to detect drug resistance in leukemia, lymphoma, blood, and bone marrow specimens.
Prognostic markers measure the tumor’s growth potential or ability to invade other tissues (metastasis). Tumor cells release proteases and angiogenic factors to break down basement membranes and induce new vascularization of the tumor, which delivers oxygen and nutrients to the tumor and allows micrometastasis to distant sites.
Predictive markers identify specific mechanisms of drug resistance and provide information on how effective clinically indicated chemotherapy agents will be in treating the patient’s tumor cells. Prognostic and predictive markers use molecular probes to determine the genetic characteristics, amount of protein, proliferation index, resistance mechanisms, receptor status, and other defining factors of the patient’s malignant tumor. To obtain the most comprehensive analysis of the patient’s unique tumor biology, drug resistance testing is done in combination with oncoprofiles and prognostic and predictive markers for the specific cancer type. A radiation resistance assay can also be done before the treatment actually begins.
These combined studies identify cervical cancer resistive to internal and external radiation plus chemotherapy (the standard treatment is prognostic indicators of progression-free survival). Also included are p53, thrombospondin-1 (Tsp-1), CD31, and angiogenesis index (AI). Prognostic and predictive markers are as follows:
Androgen receptor. This receptor predicts prostate cancer’s response to hormone therapy.
AI (p53, Tsp-1, CD31). The AI defines a patient’s risk for occult metastatic disease and is composed of factors that characterize the capacity for new blood vessel formation: p53, Tsp-1, and CD31 (vessel count). The p53 gene contributes to tumor growth suppression by slowing cell cycle progression and promoting apoptosis in damaged tumor cells. It also suppresses tumor angiogenesis. Tsp-1 levels have been found to decrease after the tumor sustains mutations in p53. CD31 is expressed on the membrane of endothelial cells, allowing for microvessel count in the tumor.
BAX. Increased levels of BAX, a 21-kD protein and amino acid, indicate accelerated programmed cell death induced by apoptotic stimulus.
Proto-oncoprotein bcl2 (apoptosis regulator). The translocation of the bcl2 gene, occurring in follicular lymphomas, is brought under control of the immunoglobulin gene promoter, resulting in increased intracellular levels of bcl2 protein. This protein suppresses programmed cell death (apoptosis). Induction of cell death is an important mechanism for many chemotherapeutic agents. An abnormal expression of bcl2 protein can render tumor cells resistant to chemotherapeutic agents.
Cathepsin D (invasion potential). Cathepsin D, a lysosomal acid protease, has been associated with metastatic potential. Elevated levels of cathepsin D are predictors of early recurrence and death in node-negative cancer and breast cancer.
CD31 (component of tumor AI). CD31 stains microvessels, allowing for counting, and helps to predict more aggressive disease, metastases, poor survival, and new vascularization of the tumor mass.
DNA ploidy and S-phase (flow cytometry). DNA ploidy and proliferative index are independent indicators of prognosis. Patients with aneuploid tumors or high S-phase fractions (SPFs) have poor disease-free survival compared with patients with diploid or low SPF tumors. DNA ploidy (image analysis) (Feulgen stain) is an indicator of prognosis in selected tumor types in fresh specimens.
Epidermal growth factor receptor (EGFR). This growth factor receptor is a glycoprotein tyrosine kinase, either EGF or transforming growth factor alpha. When high levels occur in breast, prostate, ovarian, lung, and squamous cell carcinomas, there is an association with poorer prognosis and poor disease-free survival.
Endoglin (CD105). Endoglin normally occurs in vascular endothelial cells of capillaries, arterioles, small arteries, and venules. Increased levels are found in tumor vessels and proliferating endothelial cells. Endoglin has been found in non-T/non-B and pre-B acute lymphoblastic leukemia and acute myelocytic and myelomonocytic leukemia cells.
Estrogen receptor (ER) and progesterone receptor (PR). ER and PR positivity is associated with a 70% response rate to antihormonal therapy. In contrast, the response rate is less than 10% among patients whose tumors are ER and PR negative. Patients whose tumors are ER and PR positive generally achieve superior disease-free survival.
Glutathione S-transferase (GST) (alkylator resistance). GST is an enzyme that inactivates certain anticancer agents by linking glutathione to the drug. Increased GST levels are associated with tumor resistance to chlorambucil and melphalan.
HER2/neu c-erbB2 oncoproteins. The presence of HER2/neu, a protein that functions as an oncogene, is associated with poorer prognosis. HER2/neu detection also provides information on the potential treatment response to trastuzumab (Herceptin).
Ki-67 (proliferative index). This is a staining technique. Monoclonal antibody Ki-67 is associated with increased cell proliferative activity in tumors and with more aggressive tumors and poor disease-free survival.
MDR-1 (P170 glycoprotein: multidrug resistance). The presence of MDR-1 cancer cells is associated with resistance to naturally produced chemotherapeutic agents such as paclitaxel (Taxol), doxorubicin, and etoposide and plays a critical role in the selection of a treatment regimen.
O(6)-methylguanine-DNA methyltransferase (MGMT) (nitrosourea resistance). MGMT, a repair protein, occurs after DNA damage caused by nitrosoureas, such as bis-chloroethylnitrosourea. Patients with brain cancer with high levels of the MGMT gene and alkyltransferase have shorter disease-free and overall survival.
Multidrug resistance protein. This protein is similar to, but distinct from, MDR-1 and is strongly associated with resistance to cisplatin drugs in ovarian cancer.
p21. A protein-like tumor suppressor like p53, p21 controls when and how the cell replicates. Low levels of p21 are associated with increased risk for tumor occurrence, and the absence of p21 contributes to aggressive growth in some tumors.
p53 (cell cycle and Tsp-1 regulator). The tumor suppressor gene p53 regulates cell cycle progression, cellular proliferation, DNA repair, apoptosis, and angiogenesis. Increased levels of mutated p53 protein in tumor cell nuclei are associated with tumor progression and a poorer prognosis.
Proliferating cell nuclear antigen (PCNA) (proliferative index). Presence of PCNA protein is associated with cell proliferation, and increased levels occur with more aggressive tumors and are associated with poor disease-free survival.
Thymidylate synthase (TS; 5-fluorouracil [5-FU] resistance). Drug resistance test of TS, a cellular enzyme essential for DNA biosynthesis and cell proliferation that is a target for 5-FU, is an important component of some breast cancer and colon cancer treatment regimens. Increased TS expression correlates with poorer response rates to 5-FU and with shorter survival in breast and colon cancer.
Tsp-1. This extracellular matrix protein is involved in wound healing. Low value is associated with increased tumor neovascularity and mutant p53 expression.
UIC2 (MDR-1) shift assay. This staining technique can be performed on solid tumors. The UIC2 shift assay can be performed on blood and bone marrow specimens from patients with acute myelogenous leukemia, multiple myeloma, or lymphoma and, if the sample contains an adequate amount of viable tumor cells, on solid tumors.
Vascular endothelial growth factor (VEGF). VEGF, or vascular permeability factor, plays an important role in angiogenesis, which promotes tumor progression and metastasis.
Oncoprofiles provide the maximum useful information from a single biopsy specimen. These disease-specific marker studies include tests that have been associated with clinical outcomes for each cancer type. Oncoprofiles identify relative risk for relapse and assist in planning therapy for each patient’s specific tumor. Table 11.1 shows an example of oncoprofiles.
Pretest Patient Care
Explain the purpose and biopsy procedure and obtain or confirm a signed, witnessed consent form.
Remember that patient preparation depends on the predetermined biopsy site. Complete blood count, prothrombin time (PT), and other bleeding time determinants may be required. Obtain a pertinent history (e.g., prior radiation therapy, other cancer, current medications, pregnancy).
Follow Chapter 1 guidelines for safe, effective, and informed pretest care.
Clinical Alert
Contraindications to tissue biopsy depend on the body site sampled: bleeding diathesis, anticoagulant therapy, highly vascular lesions, sepsis, seriously impaired lung function, an uncooperative patient, or local infection near the biopsy site
Posttest Patient Care
Review test results; report and record findings. Modify the nursing care plan as needed.
Monitor for signs of bleeding, inflammation, infection, laceration of tissue and organs, and perforation. Treat pain, which may be experienced to various degrees depending on the body site sampled.
Counsel the patient about follow-up procedures and treatment for infections and malignant conditions.
Follow the guidelines in Chapter 1 for safe, effective, and informed posttest care.