Yoon Sung Bae

Reduced-phase dual-illumination interferometer for measuring large stepped objects

We present a reduced-phase dual-illumination interferometer (RPDII) that measures the topography of a sample with large step height variation. We experimentally demonstrate the basic principle and the feasibility of this novel single-shot quantitative phase imaging. Two beams of this interferometer illuminate a sample at different incident angles, and two phases of the different incident angles and their phase difference are simultaneously recorded using three spatial frequencies. The relative phase difference between two beams of an RPDII can be controlled by adjusting the angle such that the maximum phase difference is smaller than 2π, and thus there is no phase wrapping ambiguity in the reconstructed phase. One 4f optical system with a transmission grating is used to illuminate the sample with two collimated beams incident at different angles. The feasibility of this technique is demonstrated by measuring the thicknesses of two stepped metal layers with heights of 150 and 660 μm. Although the change in stepped height is more than 1000 times the wavelength of the laser used in our interferometer, the thicknesses of these two metal layers are successfully obtained without the use of an unwrapping algorithm.

Usefulness of immunohistochemistry for microsatellite instability screening in gastric cancer

Background/Aims The usefulness of immunohistochemistry to screen for the microsatellite instability (MSI) phenotype in gastric cancer remains unclear. Moreover, the prognostic value of MSI phenotypes in gastric cancer has been debated. Methods The clinicopathologic parameters and survival outcomes of 203 MSI-high (MSI-H) and 261 microsatellite-stable (MSS) advanced gastric cancers (AGCs) were compared. Next, we compared the immunohistochemistry results for hMLH1 and hMSH2 with those of a polymerase chain reaction (PCR)-based method. Kaplan-Meier curves and a Cox proportional hazard regression model were used to conduct survival analyses. Results The MSI-H AGCs were correlated with older age (p<0.001), female gender (p=0.018), distal location (p<0.001), larger size (p=0.016), and intestinal type (p<0.001). Multivariate analysis revealed that the MSI-H phenotype was an independent favorable factor that was related to overall survival in patients with AGC (p<0.001). Compared with the PCR-based analysis, immunohistochemistry exhibited high sensitivity (91.1%) and specificity (98.5%) in the detection of MSI phenotypes. Conclusions MSI-H gastric cancers have distinct clinicopathologic features and better prognoses, which suggests the necessity of MSI analysis in gastric cancer. Immunohistochemistry can be a useful and reliable screening method in the assessment of MSI status in gastric cancer.

Usefulness of Ki-67 (MIB-1) immunostaining in the diagnosis of pulmonary sclerosing hemangiomas

Pulmonary sclerosing hemangioma (PSH) is an uncommon lung neoplasm with a clinical outcome that is generally benign. However, differentiating PSH from pulmonary carcinoma is sometimes difficult as both lesions share similar histopathologic and immunohistochemical features. In this study, we investigated the usefulness of Ki‐67 (MIB‐1) immunostaining in the diagnosis of PSH. We compared the staining pattern for Ki‐67 (MIB‐1) in 29 cases of typical PSH and 79 cases of pulmonary non‐small cell carcinoma (NSCLC) using an immunohistochemical method on formalin‐fixed paraffin‐embedded tissues. In all studied PSH cases, we noted cell membrane and cytoplasmic staining for Ki‐67 (MIB‐1), but this was not observed in any of the NSCLC cases. The Ki‐67 proliferation index was lower in PSH than in the NSCLC cases (mean, 1.1% vs mean, 5.5%; p < 0.001). These findings suggest that cell membrane and cytoplasmic staining for Ki‐67 (MIB‐1), as well as the Ki‐67 proliferation index, may be useful for distinguishing PSH from pulmonary carcinoma.

Pulmonary sclerosing haemangioma with metastatic spread to stomach.

1. Dunn TB, Noreen H, Gillingham K et al. Revisiting traditional risk factors for rejection and graft loss after kidney transplantation. Am. J. Transplant. 2011; 11; 2132–2143. 2. Ho YW, Chau KF, Choy BY et al. Hong Kong renal registry report 2010. Hong Kong J. Nephrol. 2010; 12; 81–98. 3. Kwok J, Chan GS, Lam MF et al. Determination of mismatched donor HLA in kidney transplant recipients with unknown donor HLA phenotypes. Clin. Transplant. 2010; 24; E178–E181. 4. Everly MJ. Using HLA antibody detection, monitoring, and treatment to improve long-term allograft survival. Clin. Transplant. 2010; 317–322.

PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma

To investigate the clinicopathologic characteristics and the prognostic impact of PIK3CA gene amplification in curatively resected esophageal squamous cell carcinoma (ESCC). Using 534 curatively resected ESCCs, the PIK3CA gene copy number was evaluated with fluorescent in situ hybridization. PIK3CA amplification was defined as PIK3CA/centromere 3 ratio is ≥ 2.0 or average number of PIK3CA signals/tumor cell nucleus ≥ 5.0. PIK3CA mutations in exon 9 and 20, encoding the highly conserved helical and kinase domains were assessed by direct sequencing in 388 cases. PIK3CA amplification was detected in 56 (10.5%) cases. PIK3CA amplification was significantly associated with higher T-stage (P=0.026) and pathologic stage (P=0.053). PIK3CA amplification showed a significantly shorter disease free survival (DFS) compared with that of non-amplified group (33.4 vs 63.1 months, P=0.019). After adjusting for gender, tumor location, pathologic stage, histologic grade and adjuvant treatment, PIK3CA amplification was significantly associated with a shorter DFS (adjusted hazard ratio [AHR] 1.53; 95% CI, 1.10-2.17; P=0.02). Though the statistical insignificance, PIK3CA amplification showed tendency of shorter OS (52.1 vs 96.5 moths, P=0.116). PIK3CA mutations were detected in 6 (1.5%) of 388 cases; 5 cases with exon 9 mutations in E545K while one exon 20 mutation in H1047L. PIK3CA amplification is a frequent oncogenic alteration and associated with shorter survival, suggesting its role as a prognostic biomarker in resected ESCC. PIK3CA amplification may represent a promising therapeutic target for ESCC.

Perivascular Epithelioid Cell Tumor Arising in the Sacrum: A Case Report

Perivascular epithelioid cell tumor (PEComa) is a rare and recently described neoplasm composed mainly of epithelioid cells with a characteristic perivascular pattern of arrangement.1 The diagnosis can be confirmed by immunohistochemical (IHC) staining as tumor cells express melanocytic and myogenic markers.2 These tumors can occur in a wide variety of organs including the kidney, liver, lung, uterus, and pancreas.3 We report the case of a PEComa arising from the sacral bone, which is an exceedingly rare site for a PEComa. Although there have been several reports of PEComas originating from bone, to our knowledge this is the first case report of a PEComa arising from the sacral bone.4

Abstract 2856: Fibroblast growth factor receptor 1 gene amplification as an independent prognostic factor for recurrence in patients with resected squamous cell esophageal cancer

Purpose To evaluate investigate the prognostic role of fibroblast growth factor receptor 1 (FGFR1) amplification in patients with surgically resected esophageal squamous cell carcinoma (ESCC). Patients and methods Gene copy number of FGFR1 was investigated in microarrayed tumors from 549 patients with ESCC who underwent curative esophagectomy. Gene copy number was evaluated by fluorescent in situ hybridization, and an FGFR1 amplified tumor (FGFR1 amp + ) was prespecified if one of the following criteria is fulfilled: (I) FGFR1/centromer 8 (CEN8) ration is ≥ 2.0, (II) average gene copy nucleus is ≥ 6.0, and (III) percentage of tumor cells containing ≥ 15 gene copies or large cluster is ≥ 10%. Results FGFR1 amplification was detected in 8% (44 of 549) of ESCC. The average copy number per nucleus was 2.7 (range, 0-15.5) and the mean FGFR1/CEN8 ratio was 2.2 (range, 0-6). The 5-year disease free survival of the FGFR1 amp + group was significantly shorter compared with that of the FGFR1amp - group (38.8% vs 63.7% P=0.012). In Cox proportional hazard model, patients with FGFR1 amp + had a significantly greater risk of recurrence compare to amp - group after adjusting for sex, smoking status, pathologic stage, histology, and adjuvant chemotherapy (HR 1.74; 95% CI, 1.10-2.76, P=0.018). Of note, there was a trend toward worse overall survival for FGFR1 amp + group compare to amp - group (5-year OS 32.0% vs 50.8%, P=0.11). FGFR1 amp + group was significantly more likely to be smokers than FGFR1amp - group (97.7 % vs 2.3%, P=0.001). With increment of total cigarette smoking dosage, the incidence of FGFR1 amp + significantly increased (P trend =0.005). Conclusions FGFR1 amplification is an independent prognostic factor for recurrence in surgically resected ESCC. FGFR1 amplification may have potential clinical application to the development of novel therapeutic strategies for ESCC Citation Format: Hyo Song Kim, Seung Eun Lee, Yoon Sung Bae, Joo Hang Kim, Hye Ryun Kim, Dae Joon Kim, Hyunki Kim, Yoon-La Choi, Byoung Chul Cho. Fibroblast growth factor receptor 1 gene amplification as an independent prognostic factor for recurrence in patients with resected squamous cell esophageal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2856. doi:10.1158/1538-7445.AM2014-2856

Abstract 4723: Prognostic significance of EGFR expression in localized gastric cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: The role of epidermal growth factor receptor (EGFR) expression as predictive or prognostic biomarker in gastric cancer is still in controversy. The aim of this study is to find prognostic role of tumor EGFR expression in gastric cancer patients after curative resection. Methods: From January 2000 to September 2003, gastric cancer patients who received curative gastrectomy were included in this study. We retrospectively collected clinical characteristics and survival data of the patients, and analyzed EGFR expression on tissue microarrays from formalin-fixed paraffin-embedded specimens of primary tumor tissues by immunochemical staining (IHC). EGFR expression was scored to 0, 1+, 2+ or 3+ based on intensity of reactivity. Results: Of total 937 patients, 295 (31.5%) patients, 101 (10.8%) patients and 36 (3.8%) patients showed EGFR 1+, 2+, and 3+ expression by IHC, respectively. EGFR overexpression (2+/3+) is more frequently found in intestinal type than diffuse or mixed type (24.2% vs. 5.1%, P<0.001). In stage III disease according to AJCC 7th edition, unlike other stages, the patients with EGFR overexpression (2+/3+) had longer disease free survival (hazard ratio [HR], 0.639; 95% confidence interval [CI], 0.434-0.938; P=0.022) and longer overall survival (HR, 0.630; 95% CI, 0.445-0.890, P=0.009) than other patients in univariate analysis. Additionally, in 279 patients who had stage III gastric cancer with diffuse type histology and received 5-fluorouracil (5-FU) based adjuvant chemotherapy, EGFR overexpression was favorable prognostic marker for overall survival (HR, 0.365; 95% CI, 0.161-0.827; P=0.016) in multivariate analysis, while old age and lymphovascular invasion were poor prognostic factors. Conclusion: EGFR overexpression was potentially favorable prognostic biomarker for stage III gastric cancer, especially in the patients who received 5-FU based adjuvant chemotherapy. Citation Format: Ji Soo Park, Hyo Song Kim, Yoon Sung Bae, Sung Hoon Noh, Hyunki Kim. Prognostic significance of EGFR expression in localized gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4723. doi:10.1158/1538-7445.AM2014-4723

All-fiber 1-D optical stretcher for bio-cells implemented in a Lab-on-a-Chip

We propose an optical stretcher based on all-fiber technology combined with Lab-on-a-Chip system for diagnosing bio-samples. Optical momentum transfer between the medium and cell surfaces induced stretching mechanical force along the beam direction. Non-diffracting beam was realized by multimode interference in optical fiber to provide a better efficiency than conventional Gaussian beam in the stretching ability. Simulation and experimental result are discussed.