The use of stained cytologic direct smears for ALK gene rearrangement analysis of lung adenocarcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100150/1/cncy21286.pd

Comparative study of TERT promoter mutation status within spatially, temporally and morphologically distinct components of urothelial carcinoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141213/1/his13318.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141213/2/his13318_am.pd

Application of immunocytochemistry and BRAF mutational analysis to direct smears of metastatic melanoma

BACKGROUND: The cytodiagnosis of melanoma in fine‐needle aspiration (FNA) specimens can be challenging, often requiring the use of immunocytochemistry. As constitutively activating mutations in the BRAF oncogene are present in at least 40% of melanomas, the use of FNA material to interrogate the BRAF mutational status is likely to increase. Because cell blocks, traditionally used for these studies, can occasionally exhibit insufficient tumor cellularity, the authors investigated the utility of direct smears for immunocytochemistry and BRAF mutational analysis. METHODS: Immunocytochemistry for S‐100, HMB‐45, and Mart‐1 was prospectively performed on direct smears in 17 FNAs of metastatic melanoma. Next, BRAF sequencing was performed using DNA isolated from archived Diff‐Quik–stained direct smears for 15 cases. In parallel, sequencing was performed using DNA obtained from corresponding cell blocks. RESULTS: S‐100 positivity in the tumor cells was observed in all 17 cases. HMB‐45 and Mart‐1 positivity was noted in 81% and 88% of cases, respectively. All 3 markers were positive in 76% of cases. Next, of the 15 archived melanoma FNAs tested, BRAF mutations were observed in 8 (53%); 5 and 3 melanomas harbored the V600E and V600K mutation, respectively. Corresponding cell blocks were also tested for all 15 cases, yielding concordant BRAF results in 14 (93%); 1 cell block yielded a false‐negative result. CONCLUSIONS: Cytologic direct smears represent a robust and valuable source of cellular material for immunocytochemistry and molecular studies, especially in instances in which inadequate cell block cellularity is anticipated or encountered. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society. This study demonstrates that direct smears represent a robust and valuable source of cellular material for ancillary studies used in the cytologic diagnosis of melanoma. Direct smears can be effectively used for confirmatory immunocytochemical studies and molecular assays designed to interrogate the BRAF mutational status of melanoma, especially in scenarios in which inadequate cell block cellularity is anticipated or encountered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90193/1/20180_ftp.pd

Comparison of real‐time PCR vs PCR with fragment length analysis for the detection of CALR mutations in suspected myeloproliferative neoplasms

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152841/1/ijlh13040.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152841/2/ijlh13040_am.pd

Comparison of real‐time PCR vs PCR with fragment length analysis for the detection of CALR

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152841/1/ijlh13040.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152841/2/ijlh13040_am.pd

Activating KRAS mutations are characteristic of oncocytic sinonasal papilloma and associated sinonasal squamous cell carcinoma

Oncocytic sinonasal papillomas (OSPs) are benign tumours of the sinonasal tract, a subset of which are associated with synchronous or metachronous sinonasal squamous cell carcinoma (SNSCC). Activating EGFR mutations were recently identified in nearly 90% of inverted sinonasal papillomas (ISPs) â a related tumour with distinct morphology. EGFR mutations were, however, not found in OSP, suggesting that different molecular alterations drive the oncogenesis of these tumours. In this study, tissue from 51 cases of OSP and five cases of OSPâ associated SNSCC was obtained retrospectively from six institutions. Tissue was also obtained from 50 cases of ISP, 22 cases of ISPâ associated SNSCC, ten cases of exophytic sinonasal papilloma (ESP), and 19 cases of SNSCC with no known papilloma association. Using targeted nextâ generation and conventional Sanger sequencing, we identified KRAS mutations in 51/51 (100%) OSPs and 5/5 (100%) OSPâ associated SNSCCs. The somatic nature of KRAS mutations was confirmed in a subset of cases with matched germline DNA, and four matched pairs of OSP and concurrent associated SNSCC had concordant KRAS genotypes. In contrast, KRAS mutations were present in only one (5%) SNSCC with no known papilloma association and none of the ISPs, ISPâ associated SNSCCs, or ESPs. This is the first report of somatic KRAS mutations in OSP and OSPâ associated SNSCC. The presence of identical mutations in OSP and concurrent associated SNSCC supports the putative role of OSP as a precursor to SNSCC, and the high frequency and specificity of KRAS mutations suggest that OSP and OSPâ associated SNSCC are biologically distinct from other similar sinonasal tumours. The identification of KRAS mutations in all studied OSP cases represents an important development in our understanding of the pathogenesis of this disease and may have implications for diagnosis and therapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133586/1/path4750.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133586/2/path4750_am.pd