ISSN:
0730-2312
Keywords:
Immunohistochemistry
;
molecular pathology
;
quantitative pathology
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Cancer chemoprevention is defined as intervention by chemical agents prior to invasion to inhibit or slow the carcinogenic process. Using surrogate endpoint biomakers in chemoprevention studies may reduce the size, length and cost of clinical prospective randomized trials in high-risk populations. Intermediate biomarkers are measurable alteration in the tissures at risk and include defferentiation, genetic compostion, biochemical expression, and proliferation. Assessment is possible because invasive epithelial neoplasms are known to begin as intraepithelial proliferations with a spectrum of cellular abnormalities extending to carcinoma in situ. Genetic heterogeneity begins in the intraepithelial phase; a stochastic accumulation fenetic errors characterizes the progression of clonal evolution within the tumor through the process of invasion and metastasis. Pathologic features associated with this process include tumon classification as well as whether it is intraepithelial lesion are reported. If the neoplasm in invasion, tumor size, extent, degree of differentiation (histologic and nuclear grade), mitotic rate, vascular invasion, and lymph node involvement are evaluated. In assessing biomarkers relevant to chemoprevention, and without complete regression of the neoplasm with the chemopreventive agent or agents, measurable parameters along with histopathlogic features are applicable. Three methods readily applicable for this purpose that can be applied to paraffin-embedded, formalin-fixed tissue include quantitative pathology, immunohistocchemistry, and molecular biologic applications. These methods require some consistency in handling and processing the tissues under study; result may deteriorate due to a number of processing variables, including time to fixation, time in fixative, and fixative type. Quantitative pathology, including static image analysis, very small tumors can be studied. In addition, adjacent total DNA content. Using static image analysis, very small tumors acan be studied. In addition, adjacent intraepithelial and invasive component of tumor may be studied from a single slide. Steroid receptors, oncogences, and other proteins detectable through immunohistochemical or molecular biologic methods can be quantitated by this technique as well. Cell cycle synthethic function is assayable by both methods. Flow cytometry can calculate the total percentage of cells in S-phase, or the tumor cell S-phase fraction based on the percentage of cells detected between the G0, G1 peak and the G2 + M peak. A similar approach in generally not applicable with current image analysis equipment; however, cell cycle ralagted proteins such as MIB-1 (Ki-67 associated)can be quantified. Immunohistochemical methods can employ a wide variety of monoclonal antibodies to detect oncogene related proteins, including HER-2/neu(c-erB-2) and p53. Molecular biologic methods, including in situ hybridization, polymerse chain reaction, and in situ PCR, can have many application when applied to paraffin-embedded tissues, including tissues, including detection of viral DNA, identification and measurement of apoptosis, and difing gene deletions.
Additional Material:
3 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240590903
