Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers

Background@#Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine. @*Methods@#Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines. @*Results@#A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study.Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicroninfected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed. @*Conclusion@#Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination.Further studies are needed to understand the characteristics of immunogenicity in these populations.

Bone Biopsy Confirmed Imatinib-Induced Bone Marrow Necrosis in Patient with Gastrointestinal Tumor: A Case Report

Imatinib mesylate is an effective, small-molecule, selective tyrosine kinase inhibitor, which inhibits BCR-ABL in patients with chronic myeloid leukemia, c-kit in patients with gastrointestinal tumor (GIST), and platelet-derived growth factors in hypereosinophilic syndrome. Above all, bone marrow necrosis is a rare complication of imatinib usage. If newly developed increased opacity bone lesions are seen in patients with metastatic GIST, it is usual to consider those lesions as bone metastasis. Also, it is true that making a differential diagnosis between bone marrow change (bone marrow necrosis) and disease progression (bone metastasis) is both clinically and radiologically difficult. Because it may alter treatment options according to early distinguish bone metastasis and imatinib related-bone necrosis, a bone biopsy is recommended. Here, we report a case that a biopsy confirmed bone marrow necrosis due to imatinib, even though investigations such as magnetic resonance imaging, and whole-body bone scan indicated more favor to the metastatic lesion.

Eight-Month Follow-up After the Third Dose of BNT162b2 Vaccine in Healthcare Workers: The Question of a Fourth Dose

Background@#A fourth dose of vaccination is known to help reduce the severity and mortality rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The South Korean vaccination guidelines for the fourth dose do not include healthcare workers (HCWs) as priority candidates. We investigated the necessity of the fourth dose in South Korean HCWs based on an 8-month follow-up period after the third vaccination. @*Methods@#Changes in the surrogate virus neutralization test (sVNT) inhibition (%) score were measured at one month, four months and eight months after the third vaccination. The sVNT values were analyzed between infected and uninfected groups, and their trajectories were compared. @*Results@#A total of 43 HCWs were enrolled in this study. In total, 28 cases (65.1%) were confirmed to be infected with SARS-CoV-2 (presumed omicron variant), and all had mild symptoms. Meanwhile, 22 cases (78.6%) were infected within four months of the third dose (median, 97.5 days). Eight months after the third dose, the SARS-CoV-2 (presumed omicron variant)-infected group showed significantly higher sVNT inhibition than that in the uninfected group (91.3% vs. 30.7%; P < 0.001). The antibody response due to hybrid immunity, provided by a combination of infection and vaccination, was maintained at sufficient levels for more than four months. @*Conclusion@#For HCWs who had coronavirus disease 2019 infection after completing a third vaccination, a sufficient antibody response was maintained until eight months after the third dose. The recommendation of the fourth dose may not be prioritized in subjects with hybrid immunity.

Gemcitabine and Erlotinib with or without Oxaliplatin in Previously Untreated Advanced Pancreatic Cancer: A Randomized Phase II Trial

Purpose@#Erlotinib has been the only targeted agent to show significantly improved outcomes in pancreatic adenocarcinoma when combined with gemcitabine. We aimed to evaluate whether the addition of oxaliplatin to a combination gemcitabine/erlotinib treatment conferred a clinical benefit in patients with locally advanced unresectable or metastatic pancreatic cancer. @*Materials and Methods@#Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T [gemcitabine 1000 mg/m2 and oxaliplatin 50 mg/m2 on day 1 (D1) and D8 plus erlotinib 100 mg daily for 3 weeks] or GT (gemcitabine 1000 mg/m2 on D1 and D8 plus erlotinib 100 mg daily for 3 weeks). The primary endpoint was the overall response rate (ORR). @*Results@#Between 2013 and 2016, 65 patients were assigned to a treatment group (33 in the GEMOX-T arm, 32 in the GT arm). The ORR was 18.2% [95% confidence interval (CI), 8.82–27.58] in the GEMOX-T arm and 6.2% (95% CI, 0.34–12.06) in the GT arm (p=0.051). The disease control rate was significantly superior in the GEMOX-T arm compared to the GT arm (72.7% vs. 43.8%, p=0.019). After a median follow-up of 19.7 months, the median progression-free survival (PFS) was 3.9 months for the GEMOX-T arm and 1.4 months for the GT arm (p=0.033). However, this did not translate to an improvement in overall survival. The most common grade 3 or higher hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). @*Conclusion@#The addition of oxaliplatin to a first-line gemcitabine/erlotinib regimen demonstrated higher response rates and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.

Gemcitabine and Erlotinib with or without Oxaliplatin in Previously Untreated Advanced Pancreatic Cancer: A Randomized Phase II Trial

Purpose@#Erlotinib has been the only targeted agent to show significantly improved outcomes in pancreatic adenocarcinoma when combined with gemcitabine. We aimed to evaluate whether the addition of oxaliplatin to a combination gemcitabine/erlotinib treatment conferred a clinical benefit in patients with locally advanced unresectable or metastatic pancreatic cancer. @*Materials and Methods@#Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T [gemcitabine 1000 mg/m2 and oxaliplatin 50 mg/m2 on day 1 (D1) and D8 plus erlotinib 100 mg daily for 3 weeks] or GT (gemcitabine 1000 mg/m2 on D1 and D8 plus erlotinib 100 mg daily for 3 weeks). The primary endpoint was the overall response rate (ORR). @*Results@#Between 2013 and 2016, 65 patients were assigned to a treatment group (33 in the GEMOX-T arm, 32 in the GT arm). The ORR was 18.2% [95% confidence interval (CI), 8.82–27.58] in the GEMOX-T arm and 6.2% (95% CI, 0.34–12.06) in the GT arm (p=0.051). The disease control rate was significantly superior in the GEMOX-T arm compared to the GT arm (72.7% vs. 43.8%, p=0.019). After a median follow-up of 19.7 months, the median progression-free survival (PFS) was 3.9 months for the GEMOX-T arm and 1.4 months for the GT arm (p=0.033). However, this did not translate to an improvement in overall survival. The most common grade 3 or higher hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). @*Conclusion@#The addition of oxaliplatin to a first-line gemcitabine/erlotinib regimen demonstrated higher response rates and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.

Epigenetic inactivation of RUNX3 in colorectal cancer

PURPOSE: Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. METHODS: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. RESULTS: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). CONCLUSION: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

Association Between c-Met and Lymphangiogenic Factors in Patients With Colorectal Cancer

PURPOSE: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. METHODS: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed. RESULTS: Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found. CONCLUSION: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.

CORRIGENDUM: Correction of funding statement in ACKNOWLEDGEMENTS section: Epigenetic inactivation of RUNX3 in colorectal cancer

Correction of funding statement in ACKNOWLEDGEMENTS section.

The incidence of venous thromboembolism is not lowin Korean patients with advanced pancreatic cancer

BACKGROUND: Pancreatic cancer is among the most common malignancies associated with venous thromboembolism (VTE). Asian patients are known to have a lower incidence of VTE compared to Caucasian patients. However, few studies have investigated the incidence of VTE in Asian patients with pancreatic cancer. METHODS: This retrospective review of medical records was performed on 505 patients with histopathologically proven advanced stage pancreatic cancer, from January 2006 to December 2012, at Soonchunhyang University Hospitals. RESULTS: Ninety-four patients (18.6%) had at least one pulmonary embolism (PE), deep vein thrombosis (DVT), or splanchnic vein thrombosis (SVT); 38 patients had isolated SVT; and 56 patients (11.1%) had at least one classic VTE (PE and/or DVT of lower extremities). Patients with more advanced stages of pancreatic cancer (distant metastatic stage, recurrence) or who had received chemotherapy had a higher incidence of classic VTE. Patients who were simultaneously diagnosed with pancreatic cancer and classic VTE had a poorer prognosis than patients with subsequent VTEs. There was a significant difference in overall survival (OS) between the presence and absence of a concurrent classic VTE diagnosis (median: OS, 2.1 mo vs. 10.7 mo; P < 0.001). Even when VTE included SVT, the result was similar (P < 0.001). CONCLUSION: In Korean patients with advanced pancreatic cancer, the incidence of VTEs is comparable to that of Caucasian patients. We also found that pancreatic cancer patients with concurrent VTEs had a poor prognosis compared to patients who developed VTEs later.

Clinicopathologic and Prognostic Significance of Transducin-Like Enhancer of Split 1 Protein Expression in Invasive Breast Cancer / 한국유방암학회지

PURPOSE: Transducin-like enhancer of split 1 (TLE1) is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. We investigated the prognostic significance of TLE1 protein expression in breast cancers by using immunohistochemistry and explored the relationship of TLE1 with clinicopathological parameters. METHODS: Immunohistochemistry was performed on 456 cases of breast cancer tiled on tissue microarrays. The relationship between TLE1 expression in normal breast specimens and ductal carcinoma in situ (DCIS) was also analyzed. RESULTS: TLE1 was highly expressed in 57 of 456 (12.5%) carcinoma samples. TLE1 was more frequently expressed in DCIS and invasive breast cancers than in normal breast tissue (p=0.002). High expression of TLE1 significantly correlated with negative lymph node (LN) metastasis (p=0.007), high histologic grade (p<0.001), estrogen receptor negativity (p<0.001), progesterone receptor negativity (p<0.001), human epidermal growth factor receptor 2 (HER2) positivity (p<0.001), and high Ki-67 proliferation index (p<0.001). Based on intrinsic subtypes, high TLE1 expression was strongly associated with HER2+ and triple-negative breast cancers (TNBC) (p<0.001). Survival analysis demonstrated no significant association between TLE1 expression and disease-free survival (DFS) (p=0.167) or overall survival (OS) (p=0.286). In subgroup analyses, no correlation was found between TLE1 expression and DFS or OS according to LN status or intrinsic subtype. CONCLUSION: High TLE1 expression is significantly associated with the HER2+ and TNBC subtypes. This is the first study documenting immunohistochemical expression of TLE1 in invasive breast cancer and its association with clinicopathological parameters, prognosis, and intrinsic subtype.

Expressions and Clinical Significances of Angiopoietin-1, Angiopoietin-2, and Tie-2 Receptor in Patients With Colorectal Cancer

PURPOSE: Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients. METHODS: We retrospectively analyzed 114 tissue samples from patients with colorectal cancer by using immunohistochemistry (IHC) to examine Ang-1, Ang-2, and Tie-2 expressions and to investigate the relationship between those expressions and clinical parameters or overall survival of such patients. A Western blot analysis was used for Ang-2 expression. RESULTS: IHC staining showed a link between Ang-1 and Tie-2 (P = 0.018), as well as meaningful correlations between Ang-2 and Tie-2 receptor (P = 0.022) and between lymph-node metastasis and Ang-2 (P = 0.025). The stronger the IHC staining for Ang-2 expression was, the shorter the cumulative survival was (P = 0.016). CONCLUSION: A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer.

Cervical Radiculopathy: Incidence and Treatment of 1,420 Consecutive Cases

STUDY DESIGN: Retrospective case series. PURPOSE: To determine the incidence of cervical radiculopathy requiring operative intervention by level and to report on the methods of treatment. OVERVIEW OF LITERATURE: Cervical radiculopathy is a common cause of pain and can result in progressive neurological deficits. Although the pathology is well understood, the actual incidence of cervical radiculopathy at particular spinal levels ultimately requiring operative intervention is unknown. METHODS: A large consecutive series of patients operated on by a single surgeon were retrospectively analyzed. The incidence of cervical radiculopathy at each level was defined for every patient. Procedures used for operative treatment were noted. Health related quality of life (HRQL) scores were collected both pre-operatively and postoperatively. RESULTS: There were 1305 primary and 115 revision operations performed. The most common primary procedures performed were anterior cervical discectomy and fusion (ACDF, 50%) and anterior cervical corpectomy and fusion (ACCF, 28%). The most commonly affected levels were C6 (66%) and C7 (62%). Reasons for revision were pseudarthrosis (27%), clinical adjacent segment pathology (CASP, 63%), persistent radiculopathy (11%), and hardware-related (2.6%). The most common procedures performed in the revision group were posterior cervical decompression and fusion (PCDF, 42%) and ACDF (40%). The most commonly affected levels were C7 (43%) and C5 (30%). Among patients that had their index surgery at our institution, the revision rate was 6.4%. In both primary and revision cases there was a significant improvement in Neck Disability Index and visual analogue scale scores postoperatively. Postoperative HRQL scores in the revision cases were significantly worse than those in the primary cases (p <0.01). CONCLUSIONS: This study provides the largest description of the incidence of cervical radiculopathy by level and operative outcomes in patients undergoing cervical decompression. The incidence of CASP was 4.2% in 3.3 years in this single institution series.

Osteotomies in the Cervical Spine

Rigid cervical deformities are difficult problems to treat. The goals of surgical treatment include deformity correction, achieving a rigid fusion, and performing a thorough neural decompression. In stiff and ankylosed cervical spines, osteotomies are required to restore sagittal and coronal balance. In this chapter, we describe the clinical and radiographic workup for patients with cervical deformities, and delineate the various factors that must be considered when planning surgical treatment. We also describe in detail the various types of cervical osteotomies, along with their surgical technique, advantages, and potential complications.

Expression of Programmed Death Receptor Ligand 1 with High Tumor-Infiltrating Lymphocytes Is Associated with Better Prognosis in Breast Cancer / 한국유방암학회지

PURPOSE: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis. METHODS: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas. RESULTS: High PD-L1 expression was demonstrated in 63 of 465 tumors (13.5%). High PD-L1 expression was significantly associated with high histologic grade (p<0.001), negative lymph nodes (p=0.011), early pathologic stage (p=0.025), high tumor-infiltrating lymphocyte (TIL) (p<0.001) counts, negative estrogen receptor (p<0.001) and progesterone receptor (p=0.002) expression, positive human epidermal growth factor receptor 2 (HER2) (p=0.003), cytokeratin 5/6 (p=0.011), epidermal growth factor receptor (p<0.001), and p53 (p<0.001) expression, and high Ki-67 proliferating index (p<0.001). Based on intrinsic subtypes, high PD-L1 expression and high TIL counts were significantly associated with the HER2 and triple-negative basal type (p<0.001). PD-L1 expression was significantly associated with better disease-free survival (DFS) (p=0.041) and overall survival (OS) (p=0.026) in the univariate analysis, but not in the multivariate analysis. Higher TIL levels was an independent prognostic factor for decreased disease progression (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.284–4.445; p=0.006) and overall death (HR, 3.666; 95% CI, 1.561–8.607; p=0.003). CONCLUSION: PD-L1 protein expression in breast cancer is associated with better DFS and OS, but is not an independent prognostic factor. High PD-L1 expression was significantly associated with high TIL levels. This finding has important implications for antibody therapies targeting the PD-1/PD-L1 signaling mechanism in breast cancer.

Intrathecal Trastuzumab Treatment in Patients with Breast Cancer and Leptomeningeal Carcinomatosis / Journal of the Korean Cancer Association, 대한암학회지

Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.

Intrathecal Trastuzumab Treatment in Patients with Breast Cancer and Leptomeningeal Carcinomatosis / Journal of the Korean Cancer Association, 대한암학회지

Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.

A Review of Complications and Outcomes following Vertebral Column Resection in Adults

The correction of rigid spinal deformities in adult patients can require a three-column osteotomy (pedicle subtraction osteotomy [PSO] or vertebral column resection [VCR]) to obtain spinal balance. Unfortunately, the existing adult deformity literature frequently reports the outcomes and complications of these procedures together even though VCR is a more extensive procedure with potentially higher rates of complications. We sought to address this shortcoming and provide clinicians with an overview of the existing literature regarding VCR in adult patients. The goals of this review are: to determine the rate of overall and neurologic complications following VCR, the rate of complications with VCR compared to PSO, and the impact of VCR on clinical and radiographic outcomes. An electronic literature search was used to identify studies reporting outcomes or complications following VCR in adult patients. Raw data on patient demographics, case information, radiographic outcomes, complications and clinical outcomes were extracted. Data were pooled to report a rate of overall complications and neurologic complications. A pooled relative risk of complications following PSO vs. VCR was also calculated. Eleven retrospective studies (Level IV) met our inclusion criteria. The overall rate of complications was 69.2%. The reoperation rate was 9.6%. The rate of neurologic complications was 13.3% (range, 6.3% to 15.8%) with most cases being transient. The rate of permanent neurologic deficits was 2.0%. We found a significantly higher rate of all complications with VCR compared to PSO (relative risk, 1.36; 95% confidence interval, 1.24-1.49; p<0.001). All studies reporting clinical outcomes showed significant improvements in functional outcome postoperatively.

High EZH2 Protein Expression Is Associated with Poor Overall Survival in Patients with Luminal A Breast Cancer / 한국유방암학회지

PURPOSE: The enhancer of zeste homologue 2 (EZH2) is a catalytic subunit of the polycomb repressive complex 2, a highly conserved histone methyltransferase. EZH2 overexpression has been implicated in various malignancies, including breast cancer, where is associated with poor outcomes. This study aims to clarify nuclear EZH2 expression levels in breast cancers using immunohistochemistry (IHC) and correlate these findings with clinicopathologic variables, including prognostic significance. METHODS: IHC was performed on tissue microarrays of 432 invasive ductal carcinoma (IDC) tumors. Associations between EZH2 expression, clinicopathologic characteristics, and molecular subtype were retrospectively analyzed. The relationship between EZH2 protein expression in normal breast tissue and ductal carcinoma in situ (DCIS) was also assessed. RESULTS: High EZH2 expression was demonstrated in 215 of 432 tumors (49.8%). EZH2 was more frequently expressed in DCIS and IDC than in normal breast tissue (p=0.001). High EZH2 expression significantly correlated with high histologic grade (p<0.001), large tumor size (p=0.014), advanced pathologic stage (p=0.006), negative estrogen receptor status (p<0.001), positive human epidermal growth factor receptor 2 (HER2) status (p<0.001), high Ki-67 staining index (p<0.001), positive cytokeratin 5/6 status (p=0.003), positive epidermal growth factor receptor status (p<0.001), and positive p53 status (p<0.001). Based on molecular subtypes, high EZH2 expression was significantly associated with HER2-negative luminal B, HER2-positive luminal B, and HER2 type and triple-negative basal cancers (p<0.001). In patients with luminal A, there was a significant trend toward shorter overall survival for those with tumors having high EZH2 expression compared to those with tumors having low EZH2 expression (p=0.045). CONCLUSION: EZH2 is frequently upregulated in breast malignancies, and it may play an important role in cancer development and progression. Furthermore, EZH2 may be a prognostic marker, especially in patients with luminal A cancer.

Second-Line Chemotherapy in Advanced Biliary Tract Cancer: A Retrospective Analysis

OBJECTIVE: The evidence of 2nd line chemotherapy has not been validated. We investigated the treatment outcomes of 2nd line palliative chemotherapy in patients with biliary tract cancer (BTC) and analyzed the factors affecting response or survival. METHODS: We retrospectively reviewed and analyzed the outcomes in advanced BTC patients who underwent 2nd line chemotherapy in Soonchunhyang Universitiy Hospitals (Bucheon, Seoul, and Cheonan). RESULTS: From December 2004 to May 2014, 65 patients were enrolled. The median age was 56 years (range, 40 to 76 years) and the ratio of cholangiocarcinoma (intrahepatic or extrahepatic), gall bladder cancer, and ampulla of Vater cancer was 41 (63.1%):18 (27.7%):6 (9.25%). Half of the patients (33 patients, 50.8%) were treated with gemcitabine-based and 28 patients (43.1%) with 5-fluorouracil- based therapy. The response rate was 3.0% and disease control rate was 21.5% in intention-to-treat analysis. Median overall survival (OS) was 7.2 months (95% confidence interval [CI], 3.9 to 10.5 months) and median progression free survival (PFS) was 3.7 months (95% CI, 2.5 to 4.9 months). In multivariate analysis, patients with good performance status (PS) (P=0.001) and chemo-sensitive tumor to 2nd line chemotherapy (P=0.000) had longer PFS as compared to the others. In addition, patients with good PS (P=0.003), chemo-sensitive tumor to 1st line (P=0.046), and 2nd line chemotherapy (P=0.004) were good prognostic factors for OS. CONCLUSION: The effect of 2nd line chemotherapy in advanced BTC was modest and maybe beneficial in select patients.

MYH9 nephropathy

MYH9-related disorder is an autosomal dominant disease caused by a mutation in the MYH9 gene, which encodes nonmuscle myosin heavy chain IIA (NMMHC-IIA). This disease is characterized by giant platelets, thrombocytopenia, granulocyte inclusion bodies, proteinuria, and high-pitch sensorineural deafness. Nephropathy has been observed in 30% of patients with MYH9-related disorder. The characteristic features are early onset proteinuria and rapidly progressing renal disorder. However, the prognosis of MYH9 nephropathy remains unclear. Herein, we describe a 36-year-old woman who presented with proteinuria and was diagnosed with MYH9 nephropathy via renal biopsy and gene analysis. Her proteinuria improved after administration of an angiotensin II receptor blocker, but was aggravated after changing to a calcium channel blocker.