Journal of Pathology and Translational Medicine

Original Articles

KRAS Mutation Test in Korean Patients with Colorectal Carcinomas: A Methodological Comparison between Sanger Sequencing and a Real-Time PCR-Based Assay: Sung Hak Lee, Arthur Minwoo Chung, Ahwon Lee, Woo Jin Oh, Yeong Jin Choi, Youn-Soo Lee, Eun Sun Jung; J Pathol Transl Med. 2017;51(1):24-31. Published online December 25, 2016; DOI: https://doi.org/10.4132/jptm.2016.10.03

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Background
Mutations in the KRAS gene have been identified in approximately 50% of colorectal cancers (CRCs). KRAS mutations are well established biomarkers in anti–epidermal growth factor receptor therapy. Therefore, assessment of KRAS mutations is needed in CRC patients to ensure appropriate treatment.
Methods
We compared the analytical performance of the cobas test to Sanger sequencing in 264 CRC cases. In addition, discordant specimens were evaluated by 454 pyrosequencing.
Results
KRAS mutations for codons 12/13 were detected in 43.2% of cases (114/264) by Sanger sequencing. Of 257 evaluable specimens for comparison, KRAS mutations were detected in 112 cases (43.6%) by Sanger sequencing and 118 cases (45.9%) by the cobas test. Concordance between the cobas test and Sanger sequencing for each lot was 93.8% positive percent agreement (PPA) and 91.0% negative percent agreement (NPA) for codons 12/13. Results from the cobas test and Sanger sequencing were discordant for 20 cases (7.8%). Twenty discrepant cases were subsequently subjected to 454 pyrosequencing. After comprehensive analysis of the results from combined Sanger sequencing–454 pyrosequencing and the cobas test, PPA was 97.5% and NPA was 100%.
Conclusions
The cobas test is an accurate and sensitive test for detecting KRAS-activating mutations and has analytical power equivalent to Sanger sequencing. Prescreening using the cobas test with subsequent application of Sanger sequencing is the best strategy for routine detection of KRAS mutations in CRC.

Citations

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Single-center study on clinicopathological and typical molecular pathologic features of metastatic brain tumor
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Assessment of KRAS and NRAS status in metastatic colorectal cancer: Experience of the National Institute of Oncology in Rabat Morocco
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Droplet digital PCR revealed high concordance between primary tumors and lymph node metastases in multiplex screening of KRAS mutations in colorectal cancer
Barbora Vanova, Michal Kalman, Karin Jasek, Ivana Kasubova, Tatiana Burjanivova, Anna Farkasova, Peter Kruzliak, Dietrich Busselberg, Lukas Plank, Zora Lasabova
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Differential Immunohistochemical Profiles for Distinguishing Prostate Carcinoma and Urothelial Carcinoma: Woo Jin Oh, Arthur Minwoo Chung, Jee Soon Kim, Ji Heun Han, Sung Hoo Hong, Ji Yeol Lee, Yeong Jin Choi; J Pathol Transl Med. 2016;50(5):345-354. Published online August 7, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.14

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Abstract PDF

Background
The pathologic distinction between high-grade prostate adenocarcinoma (PAC) involving the urinary bladder and high-grade urothelial carcinoma (UC) infiltrating the prostate can be difficult. However, making this distinction is clinically important because of the different treatment modalities for these two entities.
Methods
A total of 249 patient cases (PAC, 111 cases; UC, 138 cases) collected between June 1995 and July 2009 at Seoul St. Mary’s Hospital were studied. An immunohistochemical evaluation of prostatic markers (prostate-specific antigen [PSA], prostate-specific membrane antigen [PSMA], prostate acid phosphatase [PAP], P501s, NKX3.1, and α-methylacyl coenzyme A racemase [AMACR]) and urothelial markers (CK34βE12, p63, thrombomodulin, S100P, and GATA binding protein 3 [GATA3]) was performed using tissue microarrays from each tumor.
Results
The sensitivities of prostatic markers in PAC were 100% for PSA, 83.8% for PSMA, 91.9% for PAP, 93.7% for P501s, 88.3% for NKX 3.1, and 66.7% for AMACR. However, the urothelial markers CK34βE12, p63, thrombomodulin, S100P, and GATA3 were also positive in 1.8%, 0%, 0%, 3.6%, and 0% of PAC, respectively. The sensitivities of urothelial markers in UC were 75.4% for CK34βE12, 73.9% for p63, 45.7% for thrombomodulin, 22.5% for S100P, and 84.8% for GATA3. Conversely, the prostatic markers PSA, PSMA, PAP, P501s, NKX3.1, and AMACR were also positive in 9.4%, 0.7%, 18.8%, 0.7%, 0%, and 8.7% of UCs, respectively.
Conclusions
Prostatic and urothelial markers, including PSA, NKX3.1, p63, thrombomodulin, and GATA3 are very useful for differentiating PAC from UC. The optimal combination of prostatic and urothelial markers could improve the ability to differentiate PAC from UC pathologically.

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Classic Papillary Thyroid Carcinoma with Tall Cell Features and Tall Cell Variant Have Similar Clinicopathologic Features: Woo Jin Oh, Young Sub Lee, Uiju Cho, Ja Seong Bae, Sohee Lee, Min Hee Kim, Dong Jun Lim, Gyeong Sin Park, Youn Soo Lee, Chan Kwon Jung; Korean J Pathol. 2014;48(3):201-208. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.201

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Abstract PDF

Background

The tall cell variant of papillary thyroid carcinoma (TCVPTC) is more aggressive than classic papillary thyroid carcinoma (PTC), but the percentage of tall cells needed to diagnose TCVPTC remains controversial. In addition, little is known about the clinicopathologic features of classic PTC with tall cell features (TCF).

Methods

We retrospectively selected and reviewed the clinicopathologic features and presence of the BRAF mutation in 203 cases of classic PTC, 149 cases of classic PTC with TCF, and 95 cases of TCVPTCs, which were defined as PTCs having <10%, 10-50%, and ≥50% tall cells, respectively.

Results

TCVPTCs and classic PTCs with TCF did not vary significantly in clinicopathologic characteristics such as pathologic (p) T stage, extrathyroidal extension, pN stage, lateral lymph node metastasis, or BRAF mutations; however, these features differed significantly in TCVPTCs and classic PTCs with TCF in comparison to classic PTCs. Similar results were obtained in a subanalysis of patients with microcarcinomas (≤1.0 cm in size).

Conclusions

Classic PTCs with TCF showed a similar BRAF mutation rate and clinicopathologic features to TCVPTCs, but more aggressive characteristics than classic PTCs.

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Brief Case Report

Esophageal Squamous Cell Carcinoma In Situ Overlying Leiomyoma Mimicking Invasive Cancer: A Brief Case Report: Woo Jin Oh, Eun Jung Lee, Youn Soo Lee, Tae-Jung Kim; Korean J Pathol. 2014;48(2):162-163. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.162

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