Bong Kyung Shin

SIRT1 Expression Is Associated with Good Prognosis in Colorectal Cancer

Background Silent mating type information regulation 2 homolog 1 (SIRT1), an NAD+-dependent deacetylase, might act as a tumor promoter by inhibiting p53, but may also as a tumor suppressor by inhibiting several oncogenes such as β-catenin and survivin. Deleted in breast cancer 1 (DBC1) is known as a negative regulator of SIRT1. Methods Immunohistochemical expressions of SIRT1, DBC1, β-catenin, surviving, and p53 were evaluated using 2 mm tumor cores from 349 colorectal cancer patients for tissue microarray. Results Overexpression of SIRT1, DBC1, survivin, and p53 was seen in 235 (67%), 183 (52%), 193 (55%), and 190 (54%) patients, respectively. Altered expression of β-catenin was identified in 246 (70%) patients. On univariate analysis, overexpression of SIRT1 (p=0.029) and altered expression of β-catenin (p=0.008) were significantly associated with longer overall survival. Expression of SIRT1 was significantly related to DBC1 (p=0.001), β-catenin (p=0.001), and survivin (p=0.002), but not with p53. On multivariate analysis, age, tumor stage, differentiation, and expression of SIRT1 were independent prognostic factors significantly associated with overall survival. Conclusions SIRT1 overexpression is a good prognostic factor for colorectal cancer, and SIRT1 may interact with β-catenin and survivin rather than p53.

Correlated Expression of erbB-3 With Hormone Receptor Expression and Favorable Clinical Outcome in Invasive Ductal Carcinomas of the Breast

The prognostic impact of epidermal growth factor receptor (EGFR) family members in breast carcinoma was evaluated through the analysis of 378 cases of invasive ductal carcinoma to determine the relationship between EGFR family members and clinical outcome. It was found that 13.8% of the cases were positive for erbB-3. Expression of erbB-3 was inversely correlated with EGFR and erbB-4 expression (P = .012 and P = .046). Expression of erbB-3 was correlated with positive estrogen and progesterone receptor status and inversely correlated with histologic grade. Expression of erbB-3 was correlated with longer disease-free survival (DFS; P = .028). Within the erbB-3-expressing group, there was a tendency for the coexpressing group to have shorter DFS compared with the single-expressing group. This study revealed that erbB-3 expression was associated with better prognosis. In an era of personalized targeted therapy, erbB-3 expression and its coexpressive pattern with other EGFR family members could be an important determinant for therapeutic plans for breast cancer treatment.

Occurrence of c-kit+ tumor cells in hepatitis B virus-associated hepatocellular carcinoma

Progenitor cells, termed oval cells, are involved in the pathogenesis of hepatocellular carcinoma (HCC) in animal models. By immunolabeling for c-kit and CD34 in human hepatitis B virus-associated cirrhosis with HCC (50 cases) and those with cirrhosis alone (10 cases), we found c-kit+ tumor cells in tumor tissue in 40 of 50 HCCs. The proportion was less than 0.1% of total tumor cell volume in most HCCs. Immunostaining for c-kit also was detected in sinusoidal endothelial cells in 43 of 50 HCCs. The incidence of oval cell occurrence in the adjacent nonneoplastic tissue in cases of HCC was high (44/50). The occurrence of oval cells, c-kit+ tumor cells, and c-kit+ sinusoidal cells in cases of human hepatitis B virus-associated HCC suggests that oval cell proliferation might be associated with the development of human hepatitis B virus-associated HCC. Furthermore, the c-kit+ sinusoidal cells might have a role in angiogenesis and progression of human hepatitis B virus-associated HCC.

Large cell neuroendocrine carcinoma of the lung: radiologic and pathologic findings.

Purpose The purpose of this work was to determine the radiologic and pathologic findings of large cell neuroendocrine carcinoma (LCNEC). Method We retrospectively evaluated chest radiographs, CT scans, and pathologic findings of five patients with pathologically confirmed LCNEC. They were confirmed by percutaneous needle biopsy (n = 2) and by surgery (n = 3). The average age of patients was 60 (51–70) years, and all five were smokers (mean 30 pack-years) and men. Radiologic findings were reviewed for the pattern of lesion, location, and associated findings by two radiologists under consensus. Pathologic findings were reviewed by two pathologists. Results In all five patients, tumors were represented as a peripherally located nodule or mass without associated secondary pneumonitis or distal atelectasis radiographically. On CT scan, masses were oval or round and well demarcated with lobulated margin in all cases, their sizes ranged from 2 to 5 cm, and they did not show internal calcification and necrosis. On contrast-enhanced CT, three cases showed moderate enhancement more than the chest wall muscle. Lymphadenopathy was observed in ipsilateral hilar and mediastinal areas in three cases. Distant metastasis to liver was noted in one case. One case of LCNEC was Stage IV, two were Stage IIIa, and two were Stage Ia at the time of diagnosis. Conclusion Although the epidemiology of LCNEC is more similar to that of small cell carcinoma than atypical carcinoids, in its strong association with smoking, rapid progression, and poor prognosis, our five cases of LCNEC show peripherally located pulmonary nodule or mass with or without regional lymphadenopathy, which are findings similar to those of atypical carcinoids rather than small cell carcinoma.

Transthoracic fine needle aspiration and core biopsy of pulmonary lesions. A study of 296 patients.

OBJECTIVE To retrospectively investigate and compare the usefulness of transthoracic fine needle aspiration (FNA), core biopsy and a combination of the two in the diagnosis of pulmonary lesions. STUDY DESIGN Two hundred ninety-six patients who had undergone FNA, core biopsy or both for lung lesions were divided into malignant and benign groups according to the final diagnoses, which were based on the cytologic and histopathologic findings combined with clinical features. In each group, the diagnostic usefulness of FNA, core biopsy and a combination of the two were evaluated by comparing the results of each with the final diagnoses. RESULTS In the malignant group, FNA was diagnostically helpful in 188 of 205 patients (91.7%) and core biopsy in 158 of 180 patients (87.8%). The combination of the two methods improved the result to 172 of 178 patients (96.6%). The sensitivities were 94.6%, 88.3% and 97.2%, respectively, for each result. In the benign group, 71.1% (64/90), 70.1% (47/67) and 74.2% (49/66) of cases received specific or nonspecific diagnoses by FNA, core biopsy and their combination, respectively. The rates of specific diagnoses were 20.1%, 21.0% and 31.8%, respectively. CONCLUSION The combination of FNA and core biopsy markedly improved the diagnostic yields in the malignant group and, to a lesser degree, also in the benign group.

Cystic Lesions of the Gastrointestinal Tract: Multimodality Imaging with Pathologic Correlations

The cystic lesions of the gastrointestinal (GI) tract demonstrate the various pathologic findings. Some lesions may present a diagnostic challenge because of non-specific imaging features; however, other lesions are easily diagnosed using characteristic radiologic features and anatomic locations. Cystic masses from the GI tract can be divided into several categories: congenital lesions, neoplastic lesions (cystic neoplasms, cystic degeneration of solid neoplasms), and other miscellaneous lesions. In this pictorial review, we describe the pathologic findings of various cystic lesions of the GI tract as well as the radiologic features of GI cystic lesions from several imaging modalities including a barium study, transabdominal ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging.

Erythropoietin Attenuates Hyperoxia-Induced Lung Injury by Down-modulating Inflammation in Neonatal Rats

This study was done to determine whether recombinant human erythropoietin (rhEPO) treatment could attenuate hyperoxia-induced lung injury, and if so, whether this protective effect is mediated by the down-modulation of inflammation in neonatal rats. Newborn Sprague Dawley rat pups were subjected to 14 days of hyperoxia (>95% oxygen) within 10 hr after birth. Treatment with rhEPO significantly attenuated the mortality and reduced body weight gain caused by hyperoxia. With rhEPO treatment, given 3 unit/gm intraperitoneally at 4th, 5th, and 6th postnatal day, hyperoxia-induced alterations in lung pathology such as decreased radial alveolar count, increased mean linear intercept, and fibrosis were significantly improved, and the inflammatory changes such as myeloperoxidase activity and tumor necrosis factor-alpha expression were also significantly attenuated. In summary, rhEPO treatment significantly attenuated hyperoxia-induced lung injury by down-modulating the inflammatory responses in neonatal rats.

Stability of DNA, RNA, cytomorphology, and immunoantigenicity in Residual ThinPrep® Specimens

The aim of this study was to evaluate the quality of residual liquid‐based preparation (LBP) sample after cytopathologic diagnosis. Cervical swab, body fluid, and thyroid fine‐needle aspiration (FNA) samples preserved in ThinPrep PreservCyt® solution were tested. Samples kept frozen at −80 °C and stored at room temperature were tested 12 months after the initial sample collection. Gel electrophotography of GAPDH multiplex PCR, RNA integrity number (RIN) values obtained from Agilent bioanalyzer, cytomorphologic changes, and immunohistochemical staining (cytokeratin, thyroid transcription factor‐1 (TTF‐1), and D2‐40) were used for the evaluation of sample quality. All available samples showed successful amplification products in multiplex PCR. However, RNAs in all residual samples were degraded with low RIN values (RIN < 4). RIN values decreased rapidly when samples were stored at room temperature in LBP medium. Cytomorpholoic evaluation and immunohistochemical staining results revealed no change regardless of storage time or storage temperature. In conclusion, RNAs stored in LBP medium degraded quickly at room temperature. Residual alcohol‐based LBP cytologic specimens stored at −80 °C and room temperature showed no change in DNA quality, cytomorphology, and immunoreactivity during at least one year of storage.

Mac-2 binding protein and galectin-3 expression in mucinous tumours of the ovary: an annealing control primer system and immunohistochemical study

Aim: We used a new differential display method, the annealing control primer (ACP) system, to analyse the differentially expressed genes in mucinous ovarian tumours. To verify the corresponding target gene, immunohistochemical staining was performed on various epithelial tumours of the ovary. Methods and Results: The ACP‐based reverse transcriptase‐polymerase chain reaction revealed that 21 genes were upregulated in the mucinous ovarian adenoma and 14 genes were upregulated in the mucinous ovarian carcinoma. Among them, we selected one upregulated gene, the Mac‐2 binding protein (Mac‐2 BP), and verified the expression of the Mac‐2 BP and its ligand, galectin‐3, in a variety of epithelial ovarian tumours by immunohistochemistry. Positive expression of the Mac‐2 BP was significantly higher in the mucinous ovarian tumours compared to the other epithelial tumours. Mac‐2 BP expression was significantly increased in the borderline and malignant tumours compared to the benign tumours. Galectin‐3 expression was more frequent in clear cell carcinomas, serous tumours and mucinous tumours than in endometrioid and transitional tumours. However, there were no differences in galectin‐3 expression in comparisons among benign, borderline and malignant mucinous and serous tumours. Conclusion: These data indicate that the Mac‐2 BP may play a role in the development and progression of mucinous ovarian tumours.

A Case of Pemetrexed-Induced Acute Lung Injury in Non-small Cell Lung Cancer

Pemetrexed is a multitarget antifolate agent used to treat recurrent non-small cell lung cancer (NSCLC) after prior platinum-based chemotherapy. In a large phase III study, compared with docetaxel, pemetrexed was shown to have similar response rates and disease stabilization, with a better safety profile.1 Pemetrexed has not been considered as a cause of acute lung injury. However, here, we present a case of acute lung injury associated with pemetrexed in a patient with metastatic patient.