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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.
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Humanos , Biomarcadores , Codón , Neoplasias ColorrectalesRESUMEN
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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Humanos , Fosfatasa Ácida , Adenocarcinoma , Proteínas Portadoras , Coenzima A , Inmunohistoquímica , Membranas , Próstata , Seúl , Trombomodulina , Vejiga UrinariaRESUMEN
The most common BRAF mutation in thyroid cancer is c.1799T>A (p.Val600Glu), and other BRAF mutations are rarely reported. We investigated the clinicopathological features of thyroid cancer with rare BRAF mutations. A total of 2,763 patients with thyroid cancer underwent molecular testing by direct DNA sequencing for mutations in BRAF exon 15. Among them, 2,110 (76.4%) had BRAF mutations. The c.1799T>A mutation was found in 2,093 (76.9%) of 2,722 papillary carcinomas and in one of 7 medullary carcinomas. Sixteen cases (0.76%) harbored rare mutation types. Five cases had single-nucleotide substitutions, 5 cases had small in-frame deletion or insertion, and one harbored a two-nucleotide substitution. Of these mutations, 2 were novel (c.1797_1798insGAGACTACA, c.[1799T>A; 1801_1812del]). The c.1801A>C mutation was identified in 4 follicular variant papillary carcinomas and one follicular carcinoma. None of the patients with the c.1801A>C mutation showed extrathyroidal extension or lymph node metastasis. The prevalence of rare BRAF mutations was 0.76% of all BRAF-positive thyroid cancers, and the rare mutations were associated with less aggressive pathologic features. Although BRAF mutations are detected exclusively in papillary carcinoma, they are also found in medullary carcinoma and follicular carcinoma.
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Femenino , Humanos , Masculino , Persona de Mediana Edad , Secuencia de Bases , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/epidemiología , Incidencia , Datos de Secuencia Molecular , Mutación/genética , Polimorfismo de Nucleótido Simple/genética , Prevalencia , Proteínas Proto-Oncogénicas B-raf/genética , Enfermedades Raras/epidemiología , República de Corea/epidemiología , Factores de Riesgo , Neoplasias de la Tiroides/epidemiología , Biomarcadores de Tumor/genéticaRESUMEN
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 or =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 (< or =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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Humanos , Clasificación , Ganglios Linfáticos , Tasa de Mutación , Metástasis de la Neoplasia , Estudios Retrospectivos , Neoplasias de la TiroidesRESUMEN
We made a mistake in our recently published article.
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Primary tumors of the lung are uncommon in pediatric patients, particularly bronchioloalveolar carcinoma (BAC). An 11-year-old female suffering from back pain for 1 month was referred to Seoul St. Mary's Hospital for treatment of a pathologic fracture of the lumbar spine. Comprehensive evaluation disclosed numerous pulmonary metastases of rhabdomyosarcoma (stage IV). During chemotherapy, most of the lung lesions regressed, with the exception of two nodules. Wedge resections, intended for diagnosis and cure, yielded a histologic diagnosis of BAC.