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Purpose A telomerase reverse transcriptase (TERT) promoter mutation was identified in thyroid cancer. This TERT promoter mutation is thought to be a prognostic molecular marker, because its association with tumor aggressiveness, persistence/recurrence, and disease-specific mortality in papillary thyroid carcinoma (PTC) has been reported. In this study, we attempted to determine whether the impact of the TERT promoter mutation on PTC persistence/ recurrence is independent of clinicopathological parameters. Materials and Methods Using propensity score matching, 39 patients with PTC persistence or recurrence were matched with 35 patients without persistence or recurrence, with a similar age, sex, tumor size, multifocality, bilaterality, extrathyroidal extension, and lymph node metastasis. The TERT promoter and the BRAF V600E mutations were identified from PTC samples. Results The TERT promoter mutation was detected in 18% of PTC patients (13/74). No significant difference in the frequency of the TERT promoter mutation was observed between the persistence/ recurrence group and the non-recurrence group. Conclusion These results suggest that the prognostic implications of the TERT promoter mutation are dependent on clinicopathological parameters.
Background : CD44 is a cell surface receptor that has been implicated in tumor cell invasion and metastasis in a range of tumors of various organs, including breast, ovary, colon, lung, and brain. CD44 stimulates the invasive ability by interacting with matrix metalloproteinase 14 (MMP14). The expression of MMP14 on the cell surface is thought to trigger multiple proteinase cascades and to stimulate cell migration. Methods : A total 54 astrocytoma patients were eligible for this study. We performed a retrospective clinicopathological review and CD44 and MMP14 immunohistochemistry. Results : The expressions of CD44 and MMP14 were significantly correlated with the World Health Organization (WHO) grade. On univariate analysis, the WHO grade and the expression of CD44 were the significant prognostic factors affecting overall survival (OS) and disease progression free survival (DPFS). On the multivariate analysis by the Cox regression model, the only WHO grade was shown to be a significant independent prognostic factor for predicting the DPFS and OS. Conclusions : In this study, the CD44 and MMP14 expressions were related to the WHO grade of astrocytoma. The CD44 expression status was a prognostic factor for DPFS and OS on univariate analysis, but it was not an independent prognostic factor on the multivariate analysis.
Background: Epidermal growth factor receptor ( EGFR ) mutations in non-small cell lung cancers have emerged as key predictive biomarkers in EGFR tyrosine kinase inhibitor (TKI) treatment. However, a few patients with wild-type EGFR also respond to EGFR TKIs. This study investigated the factors predicting successful EGFR TKI treatment in lung adenocarcinoma patients with wild-type EGFR . Methods: We examined 66 patients diagnosed with lung adenocarcinoma carrying wide-type EGFR who were treated with EGFR TKIs. The EGFR gene copy number was assessed by silver in situ hybridization (SISH). We evaluated the clinical factors and EGFR gene copy numbers that are associated with a favorable clinical response to EGFR TKIs. Results: The objective response rate was 12.1%, while the disease control rate was 40.9%. EGFR SISH analysis was feasible in 23 cases. Twelve patients tested EGFR SISH–positive, and 11 were EGFR SISH–negative, with no significant difference in tumor response and survival between EGFR SISH–positive and –negative patients. The overall median progression-free survival (PFS) and overall survival (OS) of 66 patients were 2.1 months and 9.7 months, respectively. Female sex and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1 were independent predictors of PFS. ECOG PS 0–1 and a low tumor burden of extrathoracic metastasis were independent predictors of good OS. Conclusion: Factors such as good PS, female sex, and low tumor burden may predict favorable outcomes following EGFR TKI therapy in patients with EGFR wild-type lung adenocarcinoma. However, EGFR gene copy number was not predictive of survival.
Background : Cystic renal cell carcinoma has been reported to have a good prognosis. However, previous studies included cases of multilocular cystic renal cell carcinoma, which has an excellent prognosis, and renal cell carcinoma with cystic necrosis, which has an adverse prognosis. Therefore, we analyzed the prognostic influence of cystic change in clear cell renal cell carcinoma after excluding those morphological features. Methods : We identified 225 patients with clear cell renal cell carcinoma who underwent nephrectomy between 2001 and 2003. The clinicopathologic features were compared with clinical outcomes. Results : Cystic change in clear cell renal cell carcinoma (n = 66) was significantly associated with younger patient age (< 55), smaller tumor size (≤ 4 cm), lower pT stage (pT1, T2), M0 stage at initial diagnosis, lower tumor, node, and metastasis stage (I, II), and lower nuclear grade (1, 2). Patients with cystic change in clear cell renal cell carcinoma had significantly longer cancer-specific (p = 0.015) and progression-free survival (p = 0.004) than those without cystic change, by univariate analysis. Multivariate analysis revealed that cystic change significantly decreased the risk of cancer progression (risk ratio, 0.27; 95% confidence interval, 0.11 to 0.69). Conclusions : In patients with clear cell renal cell carcinoma, cystic change is a good independent predictor for survival.
배 경 결핵균 검출의 표준 검사는 항산균 도말 및 배양이나 검사에 소요되는 시간이 길고 파라핀 블록으로는 검사가 불가능한 단점이 있다. 최근 중합효소연쇄반응(PCR)을 이용한 검사법이 발달하면서 파라핀 블록에서 신속하게 결핵균을 검출할 수 있게 되었다. 그러나 PCR은 DNA 추출, 시발체의 부위, 이중 PCR 또는 실시간 PCR 등에 따라 결핵균 검출의 유용성에 차이가 있다. 이에 실시간 PCR을 포함한 다양한 분자기법을 이용하여 검사의 유용성을 알아보고자 하였다. 방 법 2007년부터 2008년까지 의뢰된 검체 913건 중 46예(결핵균 배양 검사로 결핵균이 확인된 31예, 임상 및 병리 소견상 결핵을 의심할 만한 소견이 전혀 없는 10예 및 BCG 치료에 의한 BCG 육아종으로 진단된 5예)를 대상으로 5가지 방법의 PCR (PCR1, PCR2, PCR3, PCR4, PCR5)과 실시간 PCR을 시행하여 결핵균 검출에 대한 재검율, 민감도, 특이도, 진단율 등을 비교 분석하였다. 결 과 5가지 PCR 및 실시간 PCR에서 PCR4은 재검율이 13%이었고, 나머지는 재검율 0%를 보였다. PCR1은 표적이 IS6110인 이중 PCR로 민감도 74.1%, 특이도 90%, 진단율 78%이었다. PCR2는 표적이 MPB64와 IS6110인 이중 PCR로 민감도 77.4%, 특이도 80%, 진단율 78%이었다. PCR3은 표적이 RD1인 단일 PCR로 민감도 70.9% , 특이도 100%, 진단율 78%이었다. PCR4는 표적이 RD인 이중 PCR로 민감도 82.1% , 특이도 85.7%, 진단율 82.8%이었다. PCR5는 표적이 IS6110인 이중 PCR로 민감도 70.9% , 특이도 90%, 진단율 75.6%를 나타냈다. 실시간 PCR은 senX3-regX3 intergenic region을 표적으로 TaqMan probe를 사용했으며, 민감도 67.7%, 특이도 100% 및 진단율 75.6%를 보였다. BCG 치료에 의한 BCG 육아종 5예는 PCR1에서 1예(20%)가 양성이었고, PCR2에서 2예(40%)가 양성이었으며, 다른 방법에서는 모두 음성이었다. 고 찰 파라핀 블록을 이용한 결핵균 검출에 있어 PCR은 검사방법이 용이하고 검사시간이 짧은 장점이 있었다. IS6110을 표적으로 한 이중 PCR은 민감도가 높았고, RD1을 표적으로 한 단일 PCR 및 실시간 PCR은 특이도가 높았다. 결핵균 검출을 위한 PCR로 BCG에 의한 조직 반응과 결핵균 감염을 감별하기 어려우므로 임상적 고려가 필요하다.
Nuclear receptor subfamily group H member 4 (NR1H4), also known as farnesoid X receptor, has been implicated in several cellular processes in the liver and intestine. Preclinical and clinical studies have suggested a role of NR1H4 in colon cancer development; however, how NR1H4 regulates colon cancer cell growth and survival remains unclear. We generated NR1H4 knockout (KO) colon cancer cells using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (CAS9) technology and explored the effects of NR1H4 KO in colon cancer cell proliferation, survival, and apoptosis. Interestingly, NR1H4 KO cells showed impaired cell proliferation, reduced colony formation, and increased apoptotic cell death compared to control colon cancer cells. We identified MYC as an important mediator of the signaling pathway alterations induced by NR1H4 KO. NR1H4 silencing in colon cancer cells resulted in reduced MYC protein levels, while NR1H4 activation using an NR1H4 ligand, chenodeoxycholic acid, resulted in time- and dose-dependent MYC induction. Moreover, NR1H4 KO enhanced the anti-cancer effects of doxorubicin and cisplatin, supporting the role of MYC in the enhanced apoptosis observed in NR1H4 KO cells. Taken together, our findings suggest that modulating NR1H4 activity in colon cancer cells might be a promising alternative approach to treat cancer using MYC-targeting agents.
Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers (NSCLC) have emerged as a key predictive biomarker for EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. However, some patients with wild-type EGFR also responded to EGFR TKIs. This study aimed to explore predictive factors for response to EGFR-TKIs in lung adenocarcinoma patients with wild type EGFR. We examined 68 patients who were diagnosed with lung adenocarcinoma with wide type EGFR and treated with EGFR TKIs between 2009 and 2013. These patients were subsequently assigned to either responders or non-responders. Of 68 patients, 32 (47%) responded to treatment, and 36 (53%) did not. The PFS, overall survival (OS) were significantly favorable in responders (3.83 vs 1.03 months, hazard ratio (HR)=13.65, 95% confidence interval (CI), 5.89-31.64, P<0.0001; 11.7 vs. 3.0 months, HR=3.22, 95% CI, 1.83-5.67, P<0.0001, respectively). In multivariate analysis, treatment efficacy strongly affected PFS and OS, independent of covariates (HR=14.49, 95% CI, 5.86-35.84, P<0.001 and HR=2.85, 95% CI, 1.55-5.26, P=0.001, respectively). However, none of the covariates was significantly associated with better treatment efficacy. We found that some lung adenocarcinoma patients with wild type EGFR experienced favorable PFS and OS. However, none of the clinical variables that we assessed could be successfully used to predict EGFR TKI treatment efficacy. These findings highlight the need for a biomarker that predicts response of EGFR TKI in wild type EGFR NSCLC.
Background: Although histological diagnosis of pilomatricoma is not difficult because of its unique histological features, cytological diagnosis through fine-needle aspiration cytology (FNAC) is often problematic due to misdiagnoses as malignancy. Methods: We reviewed the cytological features of 14 cases of histologically-proven pilomatricoma from Korea Cancer Center Hospital, with a discussion on the diagnostic pitfalls of FNAC. Results: Among 14 cases of pilomatricoma, 10 (71.4%) were correctly diagnosed through FNAC, and two (14.3%) were misdiagnosed as carcinoma. Cytologically, all cases had easily recognizable clusters of basaloid cells and foreign body-type multinucleated cells. Although ghost cells were also found in all cases, some were inconspicuous and hardly recognizable due to their small numbers. Conclusions: An accurate diagnosis of pilomatricoma in FNAC is feasible with consideration of clinical information and close examination of ghost cells.