A M T Patricia Fetsch

Immunocytochemistry in effusion cytology: a contemporary review

Cytology plays a pivotal role in the diagnosis of pleural effusions. In many cases, immunocytochemistry (ICC) is required to elucidate the etiology of the atypical cells. Effusions are samples that present unique problems for ICC. To date there is no standardization of ICC methods for effusions and cytology in general.

Utility of the antibodies CA 19-9, HBME-1, and thrombomodulin in the diagnosis of malignant mesothelioma and adenocarcinoma in cytology

The distinction between malignant mesothelioma (MM) and adenocarcinoma (ACA) in cytologic specimens frequently is difficult, often requiring immunocytochemistry to support the diagnosis. Recent reports have proposed the utilization of antibodies to mesothelial cell clone HBME‐1 and thrombomodulin (TM), because they are immunoreactive in MM and less commonly reactive in ACA. Immunoreactivity for the monoclonal antibody CA 19‐9 has been observed in many ACAs and reportedly is absent in MM.

Melanoma-associated antigen recognized by T cells (MART-1)

HMB‐45, an antibody directed against a premelanosome glycoprotein, has thus far been considered the most specific antibody for the immunocytochemical substantiation of the diagnosis of malignant melanoma (MM). A recently described antigen, MART‐1, is a transmembrane protein that is present in normal melanocytes and widely expressed in MM. Antibodies to MART‐1 have recently become commercially available. Both HMB‐45 and MART‐1 form the basis of ongoing immunotherapy protocols at the National Institutes of Health/National Cancer Institute.

Detection of circulating tumor cells and micrometastases in Stage II, III, and IV breast cancer patients utilizing cytology and immunocytochemistry

Evaluation for circulating tumor cells and bone marrow micrometastases has generated considerable interest due to a potential association with disease recurrence and poor prognosis. In this study, we examined bone marrow and apheresis samples from Stage II, III, and IV patients (n 120) enrolled in various clinical breast cancer trials at the National Institutes of Health/National Cancer Institute. For each patient sample, two Diff‐Quik‐stained cytospins were reviewed for morphology, and approximately 1 × 106 cells were analyzed for the expression of cytokeratins using an avidin‐biotin immunoperoxidase method. Keratin‐positive malignant cells appearing as single cells or in small clusters were detected in bone marrow samples from Stage IV patients only (9/68, 13%) and detected in apheresis samples from both Stage III and IV patients (13/245, 5%). These findings indicate that the combination of cytomorphology with immunocytochemistry can be utilized for the investigation of circulating tumor cells and bone marrow micrometastases, and that positive results appear to correlate with high tumor stage/burden. Diagn. Cytopathol. 2000;22:323–328. Published 2000 Wiley‐Liss, Inc.

Anti‐α‐inhibin

Anti‐α‐inhibin, an antibody directed against a peptide hormone, has been shown to be a useful diagnostic aid in surgical pathology material for the identification of sex cord–stromal neoplasms and recently has been described in adrenocortical carcinoma (ACC). The diagnosis of ACC versus renal cell carcinoma (RCC) may be difficult morphologically, particularly in fine‐needle aspiration (FNA) material. To date, the immunohistochemical distinction of ACC from RCC is based on a panel of antibodies that include vimentin, cytokeratins, and epithelial membrane antigen. However, the reliability of this panel is weakened by inconsistent staining patterns.

Tyrosinase Immunoreactivity in Fine-Needle Aspiration Samples of Metastatic Malignant Melanoma Fixation Methods Yield Variable Results

Tyrosinase, the rate‐limiting enzyme in melanin synthesis, is a melanoma associated antigen that is recognized by both CD4+ and CD8+ T‐cells in an HLA‐restricted fashion. Peptides derived from the tyrosinase antigen currently are being utilized as a target for T‐cells in several immunotherapy protocols for metastatic malignant melanoma (MMM) at the National Institutes of Health/National Cancer Institute. Serial fine‐needle aspirations of metastatic lesions are performed to monitor the antigen expression of tyrosinase during treatment by immunostaining cytologic preparations with the monoclonal antibody T311.

Melanoma antigen expression in serial fine-needle aspiration samples in patients with metastatic malignant melanoma participating in immunotherapy clinical trials

MART‐1 and gp100 currently are utilized as targets in immunotherapy protocols for metastatic malignant melanoma (MMM). Enrollment of patients into ongoing peptide vaccination trials at the National Cancer Institute includes immunophenotyping of samples of metastatic lesions obtained by fine‐needle aspiration (FNA). As therapy progresses, immunocytochemistry is performed on serial FNAs of metastatic lesions to monitor changes in antigen expression during treatment. It is theorized that antigen expression of melanoma cells may be diminished because of selective immunodestruction of tumor cells, or perhaps intentionally, to escape immunosurveillance.