Differential Expression of Kallikrein 7 and Kallikrein 10 in Papillary Thyroid Carcinoma and Normal Thyroid Tissue.
Suqing Xie, Codrin Iacob, Nina Suslina, Ismael Reyes, Robert Suriano, Ashlie Darr, Vikas Mehta, Raj K Tiwari, Humayun Islam, Jan Geliebter. Westchester Medical Center, Valhalla, NY; New York Medical College, Valhalla; New York Eye and Ear Infirmary, Valhalla; New York Eye and Ear Infirmary, New York
Background: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy and its incidence is rising. As definitive diagnosis before surgery is often difficult, efforts have been made to identify biomarkers to distinguish PTC from benign nodules.
Design: Total RNAs from PTC and matched, normal thyroid tissue from 7 patients were analyzed with GeneChip Human Genome U133 plus 2.0 Arrays. Scanned output files were analyzed using dChip v1.3 and Affymetrix MicroArray Suite 5.0 (MAS 5.0) software. Quantitative real time RT-PCR (qRT-PCR) and western blotting for Kallikrein 7 (KLK 7) and Kallikrein 10 (KLK 10) were performed using RNA and protein from the same patients as used for microarray. Paraffin-embedded sections from 17 cases of PTC with surrounding normal tissue and a tissue array slide including 22 cases of PTC and 27 normal thyroid tissues were stained with anti-KLK 7 and KLK 10 antibodies. The results were scored 0 to 4+ based on the immunohistochemistry (IHC) density.
Results: Microarray data indicated the differential expression of 177 genes in PTC. Compared to matched normal tissue, two of Kallikrein gene family members, KLK7 and KLK 10 are significantly overexpressed in all seven PTC samples, with a fold change of 24.72 (p<0.05) and 15.66 (p<0.05), respectively. These findings were validated by qRT-PCR with a fold change of 19.0 (p<0.05) for KLK 7 and 31.63 (p<0.05) for KLK 10, and western blotting. IHC scoring revealed that KLK 7 and KLK 10 are significantly higher (p<0.01 for both) in PTC (2.78±1.12, 3.05±1.10, respectively) than those in normal thyroid tissue (1.33±0.67, 1.24±0.65, respectively). Representative PTC/normal tissue IHC for KLK 7 and KLK 10 are shown below.
Conclusions: Our initial study demonstrated that KLK7 and KLK 10 are significantly overexpressed in PTC, compared to normal thyroid tissue. These two proteins may be useful as diagnostic biomarkers for PTC, as well as for the differential diagnosis of FNA specimens. The role of these molecules in the molecular pathogenesis needs further evaluation.
Category: Head & Neck
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 156, Monday Morning