BACKGROUND:Sometimes, cytological lung cancer diagnosis is challenging because equivocal diagnoses are common. To enhance diagnostic accuracy, fluorescent in situ hybridization (FISH), DNA‐image cytometry, and quantitative promoter hypermethylation analysis have been proposed as adjuncts.METHODS:Bronchial washings and/or brushings or transbronchial fine‐needle aspiration biopsies were prospectively collected from patients who were clinically suspected of having lung carcinoma. After routine cytological diagnosis, 70 consecutive specimens, each cytologically diagnosed as negative, equivocal, or positive for cancer cells, were investigated with adjuvant methods. Suspicious areas on the smears were restained with the LAVysion multicolor FISH probe set (Abbott Molecular, Des Plaines, Illinois) or according to the Feulgen Staining Method for DNA‐image cytometry analysis. DNA was extracted from residual liquid material, and frequencies of aberrant methylation of APC, p16INK4A, and RASSF1A gene promoters were determined with quantitative methylation‐specific polymerase chain reaction (QMSP) after bisulfite conversion. Clinical and histological follow‐up according to a reference standard, defined in advance, were available for 198 of 210 patients.RESULTS:In the whole cohort, cytology, FISH, DNA‐image cytometry, and QMSP achieved sensitivities of 83.7%, 78%, 79%, and 49.6%, respectively (specificities of 69.8%, 98.2%, 98.2%, and 98.4%, respectively). Subsequent to cytologically equivocal diagnoses, FISH, DNA‐image cytometry, and QMSP definitely identified malignancy in 79%, 83%, and 49%, respectively. With QMSP, 4 of 22 cancer patients with cytologically negative diagnoses were correctly identified.CONCLUSIONS:Thus, adjuvant FISH or DNA‐image cytometry in cytologically equivocal diagnoses improves diagnostic accuracy at comparable rates. Adjuvant QMSP in cytologically negative cases with persistent suspicion of lung cancer would enhance sensitivity. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.

When there is a tumor in the parotid gland and a histological classified adenocarcinoma is found, the differential diagnosis of breast cancer metastasis should be considered.

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3615 Background: Colorectal cancer (CRC) can be either non-metastatic (locally-advanced) or metastatic, with the latter having a considerably worse prognosis. Because tissue from patients is generally available only as FFPE specimens, we investigated whether distinct molecular signatures could be obtained for these CRC types using RNA isolated from archival FFPE specimen blocks in gene expression arrays. Methods: FFPE specimens were available from 12 non-metastatic tumors and 9 primary tumors along with their matching metastases. Up to 5 10-micron sections of each were microdissected to isolate areas of tumor tissue. RNA was extracted using a proprietary procedure of Response Genetics, Inc. and was then amplified and labeled. The resulting cRNA was hybridized to the U133 plus 2.0 GeneChip. Unsupervised PCA analysis of the samples resulted in the first principal component separating 2 distinct groups, which consisted of the non-metastatic and metastatic tumors. A differentially expressed gene list between metastatic and non-metastatic CRC was determined. These data were also analyzed for differential canonical pathways using Ingenuity Pathway Analysis. Results: Hierarchical clustering analysis segregated locally advanced primary tumors and metastatic primary tumors into two clusters with distinct gene signatures. A T-test with unequal variance assumption identified 609 differentially expressed probe sets with FDR (false discovery rate) = 0.05. Comparison of primary tumors with their liver metastases using a paired T-test showed only 2 differentially expressed genes at FDR = 0.05 but 526 genes with significance p value < 0.005. Pathway analysis showed significant deregulation of VEGF, hypoxia, B Cell receptor, PI3K/AKT, ERK/MAPK and G-protein coupled receptor signaling between locally advanced and metastatic tumors. Pathway analysis of primary tumors and metastases showed deregulated TGF-b, integrin and chemokine signaling pathways. Conclusion: We have demonstrated the feasibility of identifying metastatic and non-metastatic tumors by microarray analysis using FFPE CRC tissue. This result is currently being validated in a separate larger cohort of patients. [Table: see text]

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