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Laboratoty diagnosis of cancer

A. Histologic and Cytologic Methods Histologic examination is the most important method of diagnosis. Proper histologic diagnosis is greatly aided by: Availability of all relevant clinical data Adequate preservation and sampling of the specimen In some cases, examination of the frozen specimen to detect cell surface receptors In addition to the usual fixed and paraffin-embedded sections, quick-frozen sections are employed to obtain a rapid diagnosis while the patient is still under anesthesia -Fine needle aspiration It involves aspiration of cells from a mass, followed by cytologic examination of the smear. This procedure is used most commonly with readily palpable lesions affecting the breast, thyroid, lymph nodes, and salivary glands. -Cytologic (Papanicolaou) smears These involve examination of cancer cells that are readily shed. Exfoliative cytology is used most commonly in the diagnosis of dysplasia, carcinoma in situ, and invasive cancer of the uterine cervix and also tumors of the stomach, Bronchus, and urinary bladder. B. Immunohistochemistry The availability of specific antibodies has greatly facilitated the identification of cell products or surface markers. Some examples of the utility of immunohistochemistry in the diagnosis or management of malignant neoplasms follow Categorization of undifferentiated malignant tumors Determination of site of origin of metastatic tumors Detection of molecules that have prognostic or therapeutic significance C. Flow Cytometry Flow cytometri is used routinely in the classification of leukimias and lymphomas. In this method, flourecent antibodies against cell surface molecules molecules and differntiation antigens are used to obtain the phenotype of malignant cells. D. Tumor Markers Tumor-derived or associated molecules that can be detected in blood or other body fluids. They are not primary methods of diagnosis but rather adjuncts to the diagnosis. They may also be of valued in determining the responde to therapy. Examples of tumor markers follow:

Carcinoembryogenic antigen (CEA), normally produced by fetal gut, liver, and pancreas, may be elaborated by cancers of the colon, pancreas, stomach, and breast. Less consistently, the levels are elevated in nonneoplastic conditions (e.g. alcoholic cirrhosis, hepatitis, and ulcerative colitis). Alpha-fetoprotein (AFP) is normally produced by fetal yolk sac and liver. Markedly elevated levels are noted in cancers of the lived and testicular germ cells. E. Molecular Diagnosis An increasing number of molecular techniques are being used for the diagnosis of tumors and for predicting their behaviour. 1. Diagnosis of malignant neoplasm Molecular techniques are useful in differentiating benign (polyclonal) proliferations of T or B cells from malignant (monoclonal) proliferations. 2. Prognosis of malignant neoplasms Certain genetic alterations are associated with a poor prognosis, and thus the presence of these alterations determines the patients subsquent therapy. 3. Detection of minimal residual disease After treatment of patients with leukemia or lymphoma, the presence of minimal disease or the onset of relapse can be monitored by PCR-based amplification of nucleic acid sequences unique to the malignant clone 4. Diagnosis of hereditary predisposition to cance germ-line mutations in several tumor suppressor genes are associated with a high risk of developing specific cancers. Thus, detection of these mutated alleles may allow the patient and physician to devise an aggressive screening program, consider the option of prophylactic surgery, and counseling of relatives at risk F.Molecular Profiling Tumors One of the most exciting advances in the molecular analysis of tumors has been made possible by DNA-microarray analysis. This technique allows stimultaneous measurement of the expression levels of several thousand genes.