Arachidonate 5 lipoxygenase expression in papillary thyroid carcinoma promotes invasion via MMP-9 induction.

Arachidonate 5-lipoxygenase (ALOX5) expression and activity has been implicated in tumor pathogenesis, yet its role in papillary thyroid carcinoma (PTC) has not been characterized. ALOX5 protein and mRNA were upregulated in PTC compared to matched, normal thyroid tissue, and ALOX5 expression correlated with invasive tumor histopathology. Evidence suggests that PTC invasion is mediated through the induction of matrix metalloproteinases (MMPs) that can degrade and remodel the extracellular matrix (ECM). A correlation between MMP-9 and ALOX5 protein expression was established by immunohistochemical analysis of PTC and normal thyroid tissues using a tissue array. Transfection of ALOX5 into a PTC cell line (BCPAP) increased MMP-9 secretion and cell invasion across an ECM barrier. The ALOX5 product, 5(S)-hydroxyeicosatetraenoic acid also increased MMP-9 protein expression by BCPAP in a dose-dependent manner. Inhibitors of MMP-9 and ALOX5 reversed ALOX5-enhanced invasion. Here we describe a new role for ALOX5 as a mediator of invasion via MMP-9 induction; this ALOX5/MMP9 pathway represents a new avenue in the search for functional biomarkers and/or potential therapeutic targets for aggressive PTC.

Telecytopathology for rapid preliminary diagnosis of ultrasound-guided fine-needle aspiration of thyroid nodules.

BACKGROUND: Onsite evaluation of ultrasound-guided fine-needle aspiration (USGFNA) of thyroid nodules is essential to procure adequate samples and provide initial assessment. We present our experience with onsite evaluation of USGFNA of thyroid nodules using telecytopathology. METHODS: Real-time images of Diff-Quik-stained cytology smears were obtained with an Olympus Digital camera attached to an Olympus CX41 microscope and transmitted via ethernet by a cytotechnologist to a pathologist who rendered a preliminary diagnosis while communicating with an onsite cytotechnologist over the phone. Accuracy of preliminary diagnosis was compared with final diagnosis, retrospectively. RESULTS: A total of 79 patients (mean age 48.9 year) underwent USGFNA of 100 thyroid nodules. Preliminary diagnoses of benign, suspicious/malignant, and unsatisfactory were 72%, 7%, and 21%, respectively. Of the 72 cases initially reported as benign all remained benign on the final cytology. Of the seven suspicious/malignant cases on initial cytology, five were suspicious/malignant and two were benign on final cytology. Of the 21 cases that were initially interpreted as unsatisfactory only four were reclassified as benign on final diagnosis. The accuracy rate between the final cytology and preliminary telecytopathology diagnosis was 94%. Presence of additional material on Papanicolaou-stained slides and cellblock sections was the main reason for discrepancy that accounted for six discrepant cases. CONCLUSIONS: On-site telecytopathology for thyroid USGFNAs is highly accurate compared with final cytologic evaluation. It allows pathologists to use their time more efficiently and makes onsite evaluation at a remote site possible.

Feasibility of immediate assessment of fine needle aspirates of thyroid nodules by telecytopathology.

OBJECTIVE: In this study we discuss the diagnostic accuracy and unsatisfactory rate of onsite evaluation of ultrasound-guided fine needle aspiration (USGFNA) of thyroid nodules using telecytopathology and compare it to that of a control group without telecytopathology. METHODS: This was a retrospective analysis of USGFNA of thyroid nodules over a 9-month period with and without telecytopathology. There was no randomization for selection of the groups with and without telepathologist. A single provider performed all the procedures. Real-time images of Diff Quik-stained cytology smears were obtained with an Olympus Digital camera attached to an Olympus CX41 microscope and transmitted via the Internet by a cytotechnologist to a pathologist, who communicated the preliminary diagnosis and sample adequacy. The unsatisfactory specimen rate was compared between a group whose images were transmitted (n = 45) and another group without onsite adequacy assessment (nontransmitted) (n = 47). RESULTS: A total of 92 nodules in 67 patients were aspirated with ultrasound guidance. The unsatisfactory sample rate in the transmitted group was 13% (6 out of 45) and that of the non-transmitted group was 23% (11 out of 47). In the transmitted group, the cytology specimens of 3 patients that were initially deemed inadequate by the pathologist were considered adequate after 2 additional passes. In the transmitted group, preliminary diagnosis concurred with the final diagnosis in 96% of cases. Four passes were made in the non-transmitted group, versus 2 passes in the transmitted group. CONCLUSION: Immediate assessment of USGFNA via telecytopathology assures adequacy of the cytology sample and may reduce number of passes per nodule. Preliminary onsite telecytopathology diagnosis was highly accurate when compared to final diagnosis.

Accuracy of Cytology Specimen and Needle Core Biopsies for Detection of KRAS Mutation in Non-Small Cell Carcinoma: Comparison With Resection Specimen.

BACKGROUND: Recent studies have shown that KRAS mutations are negative predictors of benefit from both adjuvant chemotherapy and anti-EGFR directed therapies for non-small cell lung carcinoma (NSCLC). Needle core biopsy, cytology specimen and resected tissue have all been used for KRAS mutational analysis of malignant lung tumors. However, studies validating the correlation between needle core biopsy/cytology specimen and resected tissue, histologic reference standard for KRAS mutational analysis are lacking. We retrospectively compared the KRAS mutation detection on cytology specimen or needle core biopsy with corresponding resected malignant neoplasm of lung, the histologic reference standard for mutational analysis. METHOD: Twenty-seven samples including 8 cell blocks, 9 cytology smears and 10 needle core biopsies, and corresponding 22 resected malignant tumor of lung were correlated for KRAS mutational analysis. In cases where cell block material did not correspond with results on resected specimen, cytology smears of corresponding cases were microdissected for isolation of DNA. RESULTS: The needle core biopsy specimens and the corresponding surgical resections showed 100% concordant results for KRAS mutational analysis. KRAS mutation was detected in 4 out of 8 cell blocks, compared to 7 out of 8 corresponding surgical resections. Low cellularity (2 cases) and failure to retrieve DNA (1case) resulted in lack of correlation in 3 cases with cell blocks. However, cytology smears in these 3 cases confirmed the KRAS mutation noted in corresponding surgical resections. Overall concordance between cytology smears and corresponding surgical resections was 89% (8 of 9 cases). KRAS mutation was detected in 1 of the 9 cytology smears and was lacking in corresponding surgically resection. CONCLUSION: Cytology specimen and needle core biopsies provide adequate material for KRAS mutational analysis. Excellent mutational analysis concordance between cytology specimen/needle core biopsies and resected tumor suggests that predictive marker based therapeutic decision need not shift to more invasive surgical procedures.