Evaluation of apoptosis in cytologic specimens

Abstract

A hallmark of neoplasia is dysregulated apoptosis, programmed cell death. Apoptosis is crucial for normal tissue homeostasis. Dysregulation of apoptotic pathways leads to reduced cytocidal responses to chemotherapeutic drugs or radiation and is a frequent contributor to therapeutic resistance in cancer. The literature pertaining to detection of apoptotic pathway constituents in cytologic specimens is reviewed herein. Virtually all methods for detecting apoptosis, including classic cytomorphologic evaluation, TUNEL assay, immunocytochemistry, and gene sequence analysis, may be applied to cytologic samples as well as tissue. Components of both intrinsic and extrinsic apoptotic pathways have been studied, including many reports examining p53 and bcl-2, as well as studies of caspase inhibitory proteins XIAP and survivin, death receptors and ligands such as Fas, Fas-ligand, and TRAIL. p53 undergoes oncogenic alteration more than any other protein; its immunocytochemical detection almost always connotes loss of its physiologic role as an inducer of apoptosis in response to a damaged genome. Several reports establish cytologic sampling as being as useful as tissue sampling. In one respect cytologic sampling is superior to tissue sampling in particular, by allowing clinicians to repeat sampling of the same tumor before and after administration of therapy; a number of reports use this approach to attempt to predict tumor response by assaying the effect of chemotherapy on the induction of apoptosis.

A Four-Year Pathology Review of the Near Total Face Transplant

“…None of the previous studies has evaluated the presence of apoptosis by detection of DNA fragmentation in VCA . TUNEL results have shown higher sensitivity for apoptotic cell detection than other available histochemical approaches , and have clearly confirmed the presence of apoptotic cells in grade III rejection. Moreover, detection of TdT positive cells in the affected tissues may help in assessment of pathological severity scores.…”

Follow‐up evaluation of radiation‐induced DNA damage in CSF disseminated high‐grade glioma using phospho‐histone H2AX antibody

“…Well‐known postirradiation cytologic changes include cytoplasmic vacuolation, multinucleation, nucleocytoplasmic enlargement, and two‐tone cytoplasm 14. In apoptotic cytological changes, such as programmed cell death, the cell becomes smaller and denser, with a pyknotic nucleus, and the nucleus often breaks apart (karyorrhexis) or shows karyolysis 19. In the present case, a patient underwent CSF cytology at about one‐year follow‐up, and the numbers of tumor cells and mitoses were retrospective observed.…”

Cytokeratin 18 (CK18) and Caspase-Cleaved CK18 (ccCK18) as Response Markers in Anticancer Therapy

“…Dysregulation of apoptotic pathways leads to reduced responses to chemotherapeutic drugs or radiation and is a frequent contributor to therapeutic resistance in cancer. Virtually all methods for detecting apoptosis, including classic cytomorphologic evaluation, TUNEL assay, immunocytochemistry, and gene sequence analysis, may be applied to cytologic samples as well as tissue (Shtilbans et al, 2010). Early morphological features of apoptosis include blebbing of the cell surface, after which cell shrinkage, cytoskeletal rearrangements, chromatin condensation, and nuclear fragmentation occur.…”